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Learning Objectives
• Name the various functions that peroxisomes perform inside the cell
Peroxisomes
A type of organelle found in both animal cells and plant cells, a peroxisome is a membrane-bound cellular organelle that contains mostly enzymes. Peroxisomes perform important functions, including lipid metabolism and chemical detoxification. They also carry out oxidation reactions that break down fatty acids and amino acids.
In contrast to the digestive enzymes found in lysosomes, the enzymes within peroxisomes serve to transfer hydrogen atoms from various molecules to oxygen, producing hydrogen peroxide (H2O2). In this way, peroxisomes neutralize poisons, such as alcohol, that enter the body. In order to appreciate the importance of peroxisomes, it is necessary to understand the concept of reactive oxygen species.
Reactive oxygen species (ROS), such as peroxides and free radicals, are the highly-reactive products of many normal cellular processes, including the mitochondrial reactions that produce ATP and oxygen metabolism. Examples of ROS include the hydroxyl radical OH, H2O2, and superoxide (O−2). Some ROS are important for certain cellular functions, such as cell signaling processes and immune responses against foreign substances. Many ROS, however, are harmful to the body. Free radicals are reactive because they contain free unpaired electrons; they can easily oxidize other molecules throughout the cell, causing cellular damage and even cell death. Free radicals are thought to play a role in many destructive processes in the body, from cancer to coronary artery disease.
Peroxisomes oversee reactions that neutralize free radicals. They produce large amounts of the toxic H2O2 in the process, but contain enzymes that convert H2O2 into water and oxygen. These by-products are then safely released into the cytoplasm. Like miniature sewage treatment plants, peroxisomes neutralize harmful toxins so that they do not cause damage in the cells. The liver is the organ primarily responsible for detoxifying the blood before it travels throughout the body; liver cells contain an exceptionally high number of peroxisomes.
Key Points
• Lipid metabolism and chemical detoxification are important functions of peroxisomes.
• Peroxisomes are responsible for oxidation reactions that break down fatty acids and amino acids.
• Peroxisomes oversee reactions that neutralize free radicals, which cause cellular damage and cell death.
• Peroxisomes chemically neutralize poisons through a process that produces large amounts of toxic H2O2, which is then converted into water and oxygen.
• The liver is the organ primarily responsible for detoxifying the blood before it travels throughout the body; as a result, liver cells contain large amounts of peroxisomes.
Key Terms
• enzyme: a globular protein that catalyses a biological chemical reaction
• free radical: Any molecule, ion or atom that has one or more unpaired electrons; they are generally highly reactive and often only occur as transient species.
Contributions and Attributions
• Vacuole. Provided by: Wikipedia. Located at: en.Wikipedia.org/wiki/Vacuole. License: CC BY-SA: Attribution-ShareAlike
• Eukaryotic Cells. Provided by: OpenStax CNX. Located at: http://cnx.org/contents/[email protected]. License: CC BY: Attribution
• Vesicles. Provided by: Wikipedia. Located at: en.Wikipedia.org/wiki/Vesicl...and_chemistry). License: CC BY-SA: Attribution-ShareAlike
• Lysosome. Provided by: Wikipedia. Located at: en.Wikipedia.org/wiki/Lysosome. License: CC BY: Attribution
• 649px-Plant_cell_structure_svg_vacuole.svg.png. Provided by: Wikipedia. Located at: commons.wikimedia.org/wiki/F...vg_vacuole.svg. License: Public Domain: No Known Copyright
• Animal Cell. Provided by: Wikipedia. Located at: commons.wikimedia.org/wiki/F...nimal_Cell.svg. License: Public Domain: No Known Copyright
• OpenStax College, Biology. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44435/latest...ol11448/latest. License: CC BY: Attribution
• reticulum. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/reticulum. License: CC BY-SA: Attribution-ShareAlike
• lumen. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/lumen. License: CC BY-SA: Attribution-ShareAlike
• 649px-Plant_cell_structure_svg_vacuole.svg.png. Provided by: Wikipedia. Located at: commons.wikimedia.org/wiki/F...vg_vacuole.svg. License: Public Domain: No Known Copyright
• Animal Cell. Provided by: Wikipedia. Located at: commons.wikimedia.org/wiki/F...nimal_Cell.svg. License: Public Domain: No Known Copyright
• OpenStax College, The Endomembrane System and Proteins. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44435/latest..._04_02_new.jpg. License: CC BY: Attribution
• OpenStax College, Biology. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44435/latest...ol11448/latest. License: CC BY: Attribution
• vesicle. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/vesicle. License: CC BY-SA: Attribution-ShareAlike
• 649px-Plant_cell_structure_svg_vacuole.svg.png. Provided by: Wikipedia. Located at: commons.wikimedia.org/wiki/F...vg_vacuole.svg. License: Public Domain: No Known Copyright
• Animal Cell. Provided by: Wikipedia. Located at: commons.wikimedia.org/wiki/File:Animal_Cell.svg. License: Public Domain: No Known Copyright
• OpenStax College, The Endomembrane System and Proteins. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44435/latest..._04_02_new.jpg. License: CC BY: Attribution
• OpenStax College, The Endomembrane System and Proteins. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44435/latest...e_04_04_03.jpg. License: CC BY: Attribution
• OpenStax College, Biology. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44435/latest...ol11448/latest. License: CC BY: Attribution
• Lysosome. Provided by: epiehonorsbiology Wikispace. Located at: http://epiehonorsbiology.wikispaces.com/Lysosome. License: CC BY-SA: Attribution-ShareAlike
• lysosome. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/lysosome. License: CC BY-SA: Attribution-ShareAlike
• enzyme. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/enzyme. License: CC BY-SA: Attribution-ShareAlike
• 649px-Plant_cell_structure_svg_vacuole.svg.png. Provided by: Wikipedia. Located at: commons.wikimedia.org/wiki/File:Plant_cell_structure_svg_vacuole.svg. License: Public Domain: No Known Copyright
• Animal Cell. Provided by: Wikipedia. Located at: commons.wikimedia.org/wiki/File:Animal_Cell.svg. License: Public Domain: No Known Copyright
• OpenStax College, The Endomembrane System and Proteins. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44435/latest..._04_02_new.jpg. License: CC BY: Attribution
• OpenStax College, The Endomembrane System and Proteins. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44435/latest...e_04_04_03.jpg. License: CC BY: Attribution
• OpenStax College, The Endomembrane System and Proteins. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44435/latest...e_04_04_04.jpg. License: CC BY: Attribution
• OpenStax College, Biology. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44407/latest...ol11448/latest. License: CC BY: Attribution
• OpenStax College, Biology. October 21, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44407/latest...ol11448/latest. License: CC BY: Attribution
• OpenStax College, The Cytoplasm and Cellular Organelles. October 22, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m46023/latest/. License: CC BY: Attribution
• enzyme. Provided by: Wiktionary. Located at: http://en.wiktionary.org/wiki/enzyme. License: CC BY-SA: Attribution-ShareAlike
• free radical. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/free_radical. License: CC BY-SA: Attribution-ShareAlike
• 649px-Plant_cell_structure_svg_vacuole.svg.png. Provided by: Wikipedia. Located at: commons.wikimedia.org/wiki/File:Plant_cell_structure_svg_vacuole.svg. License: Public Domain: No Known Copyright
• Animal Cell. Provided by: Wikipedia. Located at: commons.wikimedia.org/wiki/File:Animal_Cell.svg. License: Public Domain: No Known Copyright
• OpenStax College, The Endomembrane System and Proteins. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44435/latest..._04_02_new.jpg. License: CC BY: Attribution
• OpenStax College, The Endomembrane System and Proteins. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44435/latest...e_04_04_03.jpg. License: CC BY: Attribution
• OpenStax College, The Endomembrane System and Proteins. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44435/latest...e_04_04_04.jpg. License: CC BY: Attribution
• OpenStax College, The Cytoplasm and Cellular Organelles. October 22, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m46023/latest/. License: CC BY: Attribution | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/04%3A_Cell_Structure/4.15%3A_The_Endomembrane_System_and_Proteins_-_Peroxisomes.txt |
Learning Objectives
• Describe the structure and function of microfilaments
Microfilaments
If all the organelles were removed from a cell, the plasma membrane and the cytoplasm would not be the only components left. Within the cytoplasm there would still be ions and organic molecules, plus a network of protein fibers that help maintain the shape of the cell, secure some organelles in specific positions, allow cytoplasm and vesicles to move within the cell, and enable unicellular organisms to move independently. This network of protein fibers is known as the cytoskeleton. There are three types of fibers within the cytoskeleton: microfilaments, intermediate filaments, and microtubules. Of the three types of protein fibers in the cytoskeleton, microfilaments are the narrowest. They function in cellular movement, have a diameter of about 7 nm, and are made of two intertwined strands of a globular protein called actin. For this reason, microfilaments are also known as actin filaments.
Actin is powered by ATP to assemble its filamentous form, which serves as a track for the movement of a motor protein called myosin. This enables actin to engage in cellular events requiring motion such as cell division in animal cells and cytoplasmic streaming, which is the circular movement of the cell cytoplasm in plant cells. Actin and myosin are plentiful in muscle cells. When your actin and myosin filaments slide past each other, your muscles contract.
Microfilaments also provide some rigidity and shape to the cell. They can depolymerize (disassemble) and reform quickly, thus enabling a cell to change its shape and move. White blood cells (your body’s infection-fighting cells) make good use of this ability. They can move to the site of an infection and engulf the pathogen.
Key Points
• Microfilaments assist with cell movement and are made of a protein called actin.
• Actin works with another protein called myosin to produce muscle movements, cell division, and cytoplasmic streaming.
• Microfilaments keep organelles in place within the cell.
Key Terms
• actin: A globular structural protein that polymerizes in a helical fashion to form an actin filament (or microfilament).
• filamentous: Having the form of threads or filaments
• myosin: a large family of motor proteins found in eukaryotic tissues, allowing mobility in muscles
4.17: The Cytoskeleton - Intermediate Filaments and Microtubules
Learning Objectives
• Describe the roles of microtubules as part of the cell’s cytoskeleton
Microtubules
As their name implies, microtubules are small hollow tubes. Microtubules, along with microfilaments and intermediate filaments, come under the class of organelles known as the cytoskeleton. The cytoskeleton is the framework of the cell which forms the structural supporting component. Microtubules are the largest element of the cytoskeleton. The walls of the microtubule are made of polymerized dimers of α-tubulin and β-tubulin, two globular proteins. With a diameter of about 25 nm, microtubules are the widest components of the cytoskeleton. They help the cell resist compression, provide a track along which vesicles move through the cell, and pull replicated chromosomes to opposite ends of a dividing cell. Like microfilaments, microtubules can dissolve and reform quickly.
Microtubules are also the structural elements of flagella, cilia, and centrioles (the latter are the two perpendicular bodies of the centrosome ). In animal cells, the centrosome is the microtubule-organizing center. In eukaryotic cells, flagella and cilia are quite different structurally from their counterparts in prokaryotes.
Intermediate Filaments
Intermediate filaments (IFs) are cytoskeletal components found in animal cells. They are composed of a family of related proteins sharing common structural and sequence features. Intermediate filaments have an average diameter of 10 nanometers, which is between that of 7 nm actin (microfilaments), and that of 25 nm microtubules, although they were initially designated ‘intermediate’ because their average diameter is between those of narrower microfilaments (actin) and wider myosin filaments found in muscle cells. Intermediate filaments contribute to cellular structural elements and are often crucial in holding together tissues like skin.
Flagella and Cilia
Flagella (singular = flagellum ) are long, hair-like structures that extend from the plasma membrane and are used to move an entire cell (for example, sperm, Euglena). When present, the cell has just one flagellum or a few flagella. When cilia (singular = cilium) are present, however, many of them extend along the entire surface of the plasma membrane. They are short, hair-like structures that are used to move entire cells (such as paramecia) or substances along the outer surface of the cell (for example, the cilia of cells lining the Fallopian tubes that move the ovum toward the uterus, or cilia lining the cells of the respiratory tract that trap particulate matter and move it toward your nostrils).
Despite their differences in length and number, flagella and cilia share a common structural arrangement of microtubules called a “9 + 2 array.” This is an appropriate name because a single flagellum or cilium is made of a ring of nine microtubule doublets surrounding a single microtubule doublet in the center.
Key Points
• Microtubules help the cell resist compression, provide a track along which vesicles can move throughout the cell, and are the components of cilia and flagella.
• Cilia and flagella are hair-like structures that assist with locomotion in some cells, as well as line various structures to trap particles.
• The structures of cilia and flagella are a “9+2 array,” meaning that a ring of nine microtubules is surrounded by two more microtubules.
• Microtubules attach to replicated chromosomes during cell division and pull them apart to opposite ends of the pole, allowing the cell to divide with a complete set of chromosomes in each daughter cell.
Key Terms
• microtubule: Small tubes made of protein and found in cells; part of the cytoskeleton
• flagellum: a flagellum is a lash-like appendage that protrudes from the cell body of certain prokaryotic and eukaryotic cells
• cytoskeleton: A cellular structure like a skeleton, contained within the cytoplasm. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/04%3A_Cell_Structure/4.16%3A_The_Cytoskeleton_-_Microfilaments.txt |
Learning Objectives
• Explain the role of the extracellular matrix in animal cells
Extracellular Matrix of Animal Cells
Most animal cells release materials into the extracellular space. The primary components of these materials are proteins. Collagen is the most abundant of the proteins. Its fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. Collectively, these materials are called the extracellular matrix. Not only does the extracellular matrix hold the cells together to form a tissue, but it also allows the cells within the tissue to communicate with each other.
How does this cell communication occur? Cells have protein receptors on the extracellular surfaces of their plasma membranes. When a molecule within the matrix binds to the receptor, it changes the molecular structure of the receptor. The receptor, in turn, changes the conformation of the microfilaments positioned just inside the plasma membrane. These conformational changes induce chemical signals inside the cell that reach the nucleus and turn “on” or “off” the transcription of specific sections of DNA. This affects the production of associated proteins, thus changing the activities within the cell.
An example of the role of the extracellular matrix in cell communication can be seen in blood clotting. When the cells lining a blood vessel are damaged, they display a protein receptor called tissue factor. When a tissue factor binds with another factor in the extracellular matrix, it causes platelets to adhere to the wall of the damaged blood vessel and stimulates the adjacent smooth muscle cells in the blood vessel to contract (thus constricting the blood vessel). Subsequently, a series of steps are initiated which then prompt the platelets to produce clotting factors.
Key Points
• The extracellular matrix of animal cells is made up of proteins and carbohydrates.
• Cell communication within tissue and tissue formation are main functions of the extracellular matrix of animal cells.
• Tissue communication is kick-started when a molecule within the matrix binds a receptor; the end results are conformational changes that induce chemical signals that ultimately change activities within the cell.
Key Terms
• collagen: Any of more than 28 types of glycoprotein that forms elongated fibers, usually found in the extracellular matrix of connective tissue.
• proteoglycan: Any of many glycoproteins that have heteropolysaccharide side chains
• extracellular matrix: All the connective tissues and fibres that are not part of a cell, but rather provide support.
4.19: Connections between Cells and Cellular Activities - Intercellular Junctions
Learning Objectives
• Describe the purpose of intercellular junctions in the structure of cells
Intercellular Junctions
The extracellular matrix allows cellular communication within tissues through conformational changes that induce chemical signals, which ultimately transform activities within the cell. However, cells are also capable of communicating with each other via direct contact through intercellular junctions.
There are some differences in the ways that plant and animal cells communicate directly. Plasmodesmata are junctions between plant cells, whereas animal cell contacts are carried out through tight junctions, gap junctions, and desmosomes.
Junctions in Plant Cells
In general, long stretches of the plasma membranes of neighboring plant cells cannot touch one another because they are separated by the cell wall that surrounds each cell. How then can a plant transfer water and other soil nutrients from its roots, through its stems, and to its leaves? This transport primarily uses the vascular tissues (xylem and phloem); however, there are also structural modifications called plasmodesmata (singular: plasmodesma) that facilitate direct communication in plant cells. Plasmodesmata are numerous channels that pass between cell walls of adjacent plant cells and connect their cytoplasm; thereby, enabling materials to be transported from cell to cell, and thus throughout the plant.
Junctions in Animal Cells
Communication between animal cells can be carried out through three types of junctions. The first, a tight junction, is a watertight seal between two adjacent animal cells. The cells are held tightly against each other by proteins (predominantly two proteins called claudins and occludins). This tight adherence prevents materials from leaking between the cells. These junctions are typically found in epithelial tissues that line internal organs and cavities and comprise most of the skin. For example, the tight junctions of the epithelial cells lining your urinary bladder prevent urine from leaking out into the extracellular space.
Also found only in animal cells are desmosomes, the second type of intercellular junctions in these cell types. Desmosomes act like spot welds between adjacent epithelial cells, connecting them. Short proteins called cadherins in the plasma membrane connect to intermediate filaments to create desmosomes. The cadherins join two adjacent cells together and maintain the cells in a sheet-like formation in organs and tissues that stretch, such as the skin, heart, and muscles.
Lastly, similar to plasmodesmata in plant cells, gap junctions are the third type of direct junction found within animal cells. These junctions are channels between adjacent cells that allow for the transport of ions, nutrients, and other substances that enable cells to communicate. Structurally, however, gap junctions and plasmodesmata differ. Gap junctions develop when a set of six proteins (called connexins) in the plasma membrane arrange themselves in an elongated doughnut-like configuration called a connexon. When the pores (“doughnut holes”) of connexons in adjacent animal cells align, a channel between the two cells forms. Gap junctions are particularly important in cardiac muscle. The electrical signal for the muscle to contract is passed efficiently through gap junctions, which allows the heart muscle cells to contract in tandem.
Key Points
• Plasmodesmata are intercellular junctions between plant cells that enable the transportation of materials between cells.
• A tight junction is a watertight seal between two adjacent animal cells, which prevents materials from leaking out of cells.
• Desmosomes connect adjacent cells when cadherins in the plasma membrane connect to intermediate filaments.
• Similar to plasmodesmata, gap junctions are channels between adjacent cells that allow for the transport of ions, nutrients, and other substances.
Key Terms
• plasmodesma: A microscopic channel traversing the cell walls of plant cells and some algal cells, enabling transport and communication between them.
• connexon: An assembly of six connexins forming a bridge called a gap junction between the cytoplasms of two adjacent cells.
• occludin: Together with the claudin group of proteins, it is the main component of the tight junctions. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/04%3A_Cell_Structure/4.18%3A_Connections_between_Cells_and_Cellular_Activities_-_Extracellular_Matrix_of_Animal_Cells.txt |
• 5.1: Components and Structure - Components of Plasma Membranes
The plasma membrane protects the cell from its external environment, mediates cellular transport, and transmits cellular signals.
• 5.2: Components and Structure - Fluid Mosaic Model
The fluid mosaic model describes the plasma membrane structure as a mosaic of phospholipids, cholesterol, proteins, and carbohydrates.
• 5.3: Components and Structure - Membrane Fluidity
The mosaic nature of the membrane, its phospholipid chemistry, and the presence of cholesterol contribute to membrane fluidity.
• 5.4: Passive Transport - The Role of Passive Transport
Passive transport, such as diffusion and osmosis, moves materials of small molecular weight across membranes.
• 5.5: Passive Transport - Selective Permeability
The hydrophobic and hydrophilic regions of plasma membranes aid the diffusion of some molecules and hinder the diffusion of others.
• 5.6: Passive Transport - Diffusion
Diffusion is a process of passive transport in which molecules move from an area of higher concentration to one of lower concentration.
• 5.7: Passive Transport - Facilitated Transport
Facilitated diffusion is a process by which molecules are transported across the plasma membrane with the help of membrane proteins.
• 5.8: Passive Transport - Osmosis
Osmosis is the movement of water through a semipermeable membrane according to the concentration gradient of water across the membrane, which is inversely proportional to the concentration of solutes. Semipermeable membranes, also termed selectively permeable membranes or partially permeable membranes, allow certain molecules or ions to pass through by diffusion.
• 5.9: Passive Transport - Tonicity
Tonicity describes how an extracellular solution can change the volume of a cell by affecting osmosis. A solution’s tonicity often directly correlates with the osmolarity of the solution. Osmolarity describes the total solute concentration of the solution. A solution with low osmolarity has a greater number of water molecules relative to the number of solute particles; a solution with high osmolarity has fewer water molecules with respect to solute particles.
• 5.10: Active Transport - Electrochemical Gradient
To move substances against the membrane’s electrochemical gradient, the cell utilizes active transport, which requires energy from ATP.
• 5.11: Active Transport - Primary Active Transport
The sodium-potassium pump maintains the electrochemical gradient of living cells by moving sodium in and potassium out of the cell.
• 5.12: Active Transport - Secondary Active Transport
In secondary active transport, a molecule is moved down its electrochemical gradient as another is moved up its concentration gradient.
• 5.13: Bulk Transport - Endocytosis
Endocytosis is a type of active transport that moves particles, such as large molecules, parts of cells, and even whole cells, into a cell. There are different variations of endocytosis, but all share a common characteristic: the plasma membrane of the cell invaginates, forming a pocket around the target particle. The pocket pinches off, resulting in the particle being contained in a newly-created intracellular vesicle formed from the plasma membrane.
• 5.14: Bulk Transport - Exocytosis
Exocytosis is the process by which cells release particles from within the cell into the extracellular space.
05: Structure and Function of Plasma Membranes
Learning Objectives
• Describe the function and components of the plasma membrane
Structure of Plasma Membranes
The plasma membrane (also known as the cell membrane or cytoplasmic membrane) is a biological membrane that separates the interior of a cell from its outside environment.
The primary function of the plasma membrane is to protect the cell from its surroundings. Composed of a phospholipid bilayer with embedded proteins, the plasma membrane is selectively permeable to ions and organic molecules and regulates the movement of substances in and out of cells. Plasma membranes must be very flexible in order to allow certain cells, such as red blood cells and white blood cells, to change shape as they pass through narrow capillaries.
The plasma membrane also plays a role in anchoring the cytoskeleton to provide shape to the cell, and in attaching to the extracellular matrix and other cells to help group cells together to form tissues. The membrane also maintains the cell potential.
In short, if the cell is represented by a castle, the plasma membrane is the wall that provides structure for the buildings inside the wall, regulates which people leave and enter the castle, and conveys messages to and from neighboring castles. Just as a hole in the wall can be a disaster for the castle, a rupture in the plasma membrane causes the cell to lyse and die.
The Plasma Membrane and Cellular Transport
The movement of a substance across the selectively permeable plasma membrane can be either “passive”—i.e., occurring without the input of cellular energy —or “active”—i.e., its transport requires the cell to expend energy.
The cell employs a number of transport mechanisms that involve biological membranes:
1. Passive osmosis and diffusion: transports gases (such as O2 and CO2) and other small molecules and ions
2. Transmembrane protein channels and transporters: transports small organic molecules such as sugars or amino acids
3. Endocytosis: transports large molecules (or even whole cells) by engulfing them
4. Exocytosis: removes or secretes substances such as hormones or enzymes
The Plasma Membrane and Cellular Signaling
Among the most sophisticated functions of the plasma membrane is its ability to transmit signals via complex proteins. These proteins can be receptors, which work as receivers of extracellular inputs and as activators of intracellular processes, or markers, which allow cells to recognize each other.
Membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors, which then trigger intracellular responses. Some viruses, such as Human Immunodeficiency Virus (HIV), can hijack these receptors to gain entry into the cells, causing infections.
Membrane markers allow cells to recognize one another, which is vital for cellular signaling processes that influence tissue and organ formation during early development. This marking function also plays a later role in the “self”-versus-“non-self” distinction of the immune response. Marker proteins on human red blood cells, for example, determine blood type (A, B, AB, or O).
Key Points
• The principal components of the plasma membrane are lipids ( phospholipids and cholesterol), proteins, and carbohydrates.
• The plasma membrane protects intracellular components from the extracellular environment.
• The plasma membrane mediates cellular processes by regulating the materials that enter and exit the cell.
• The plasma membrane carries markers that allow cells to recognize one another and can transmit signals to other cells via receptors.
Key Terms
• plasma membrane: The semipermeable barrier that surrounds the cytoplasm of a cell.
• receptor: A protein on a cell wall that binds with specific molecules so that they can be absorbed into the cell. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/05%3A_Structure_and_Function_of_Plasma_Membranes/5.01%3A_Components_and_Structure_-_Components_of_Plasma_Membranes.txt |
Learning Objectives
• Describe the fluid mosaic model of cell membranes
The fluid mosaic model was first proposed by S.J. Singer and Garth L. Nicolson in 1972 to explain the structure of the plasma membrane. The model has evolved somewhat over time, but it still best accounts for the structure and functions of the plasma membrane as we now understand them. The fluid mosaic model describes the structure of the plasma membrane as a mosaic of components —including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character. Plasma membranes range from 5 to 10 nm in thickness. For comparison, human red blood cells, visible via light microscopy, are approximately 8 µm wide, or approximately 1,000 times wider than a plasma membrane. The proportions of proteins, lipids, and carbohydrates in the plasma membrane vary with cell type. For example, myelin contains 18% protein and 76% lipid. The mitochondrial inner membrane contains 76% protein and 24% lipid.
The main fabric of the membrane is composed of amphiphilic or dual-loving, phospholipid molecules. The hydrophilic or water-loving areas of these molecules are in contact with the aqueous fluid both inside and outside the cell. Hydrophobic, or water-hating molecules, tend to be non- polar. A phospholipid molecule consists of a three-carbon glycerol backbone with two fatty acid molecules attached to carbons 1 and 2, and a phosphate-containing group attached to the third carbon. This arrangement gives the overall molecule an area described as its head (the phosphate-containing group), which has a polar character or negative charge, and an area called the tail (the fatty acids), which has no charge. They interact with other non-polar molecules in chemical reactions, but generally do not interact with polar molecules. When placed in water, hydrophobic molecules tend to form a ball or cluster. The hydrophilic regions of the phospholipids tend to form hydrogen bonds with water and other polar molecules on both the exterior and interior of the cell. Thus, the membrane surfaces that face the interior and exterior of the cell are hydrophilic. In contrast, the middle of the cell membrane is hydrophobic and will not interact with water. Therefore, phospholipids form an excellent lipid bilayer cell membrane that separates fluid within the cell from the fluid outside of the cell.
Proteins make up the second major component of plasma membranes. Integral proteins (some specialized types are called integrins) are, as their name suggests, integrated completely into the membrane structure, and their hydrophobic membrane-spanning regions interact with the hydrophobic region of the the phospholipid bilayer. Single-pass integral membrane proteins usually have a hydrophobic transmembrane segment that consists of 20–25 amino acids. Some span only part of the membrane—associating with a single layer—while others stretch from one side of the membrane to the other, and are exposed on either side. Some complex proteins are composed of up to 12 segments of a single protein, which are extensively folded and embedded in the membrane. This type of protein has a hydrophilic region or regions, and one or several mildly hydrophobic regions. This arrangement of regions of the protein tends to orient the protein alongside the phospholipids, with the hydrophobic region of the protein adjacent to the tails of the phospholipids and the hydrophilic region or regions of the protein protruding from the membrane and in contact with the cytosol or extracellular fluid.
Carbohydrates are the third major component of plasma membranes. They are always found on the exterior surface of cells and are bound either to proteins (forming glycoproteins) or to lipids (forming glycolipids). These carbohydrate chains may consist of 2–60 monosaccharide units and can be either straight or branched. Along with peripheral proteins, carbohydrates form specialized sites on the cell surface that allow cells to recognize each other. This recognition function is very important to cells, as it allows the immune system to differentiate between body cells (called “self”) and foreign cells or tissues (called “non-self”). Similar types of glycoproteins and glycolipids are found on the surfaces of viruses and may change frequently, preventing immune cells from recognizing and attacking them. These carbohydrates on the exterior surface of the cell—the carbohydrate components of both glycoproteins and glycolipids—are collectively referred to as the glycocalyx (meaning “sugar coating”). The glycocalyx is highly hydrophilic and attracts large amounts of water to the surface of the cell. This aids in the interaction of the cell with its watery environment and in the cell’s ability to obtain substances dissolved in the water.
Key Points
• The main fabric of the membrane is composed of amphiphilic or dual-loving, phospholipid molecules.
• Integral proteins, the second major component of plasma membranes, are integrated completely into the membrane structure with their hydrophobic membrane-spanning regions interacting with the hydrophobic region of the phospholipid bilayer.
• Carbohydrates, the third major component of plasma membranes, are always found on the exterior surface of cells where they are bound either to proteins (forming glycoproteins ) or to lipids (forming glycolipids).
Key Terms
• amphiphilic: Having one surface consisting of hydrophilic amino acids and the opposite surface consisting of hydrophobic (or lipophilic) ones.
• hydrophilic: Having an affinity for water; able to absorb, or be wetted by water, “water-loving.”
• hydrophobic: Lacking an affinity for water; unable to absorb, or be wetted by water, “water-fearing.” | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/05%3A_Structure_and_Function_of_Plasma_Membranes/5.02%3A_Components_and_Structure_-_Fluid_Mosaic_Model.txt |
Learning Objectives
• Explain the function of membrane fluidity in the structure of cells
Membrane Fluidity
There are multiple factors that lead to membrane fluidity. First, the mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist in the membrane as separate but loosely-attached molecules. The membrane is not like a balloon that can expand and contract; rather, it is fairly rigid and can burst if penetrated or if a cell takes in too much water. However, because of its mosaic nature, a very fine needle can easily penetrate a plasma membrane without causing it to burst; the membrane will flow and self-seal when the needle is extracted.
The second factor that leads to fluidity is the nature of the phospholipids themselves. In their saturated form, the fatty acids in phospholipid tails are saturated with bound hydrogen atoms; there are no double bonds between adjacent carbon atoms. This results in tails that are relatively straight. In contrast, unsaturated fatty acids do not contain a maximal number of hydrogen atoms, although they do contain some double bonds between adjacent carbon atoms; a double bond results in a bend of approximately 30 degrees in the string of carbons. Thus, if saturated fatty acids, with their straight tails, are compressed by decreasing temperatures, they press in on each other, making a dense and fairly rigid membrane. If unsaturated fatty acids are compressed, the “kinks” in their tails elbow adjacent phospholipid molecules away, maintaining some space between the phospholipid molecules. This “elbow room” helps to maintain fluidity in the membrane at temperatures at which membranes with saturated fatty acid tails in their phospholipids would “freeze” or solidify. The relative fluidity of the membrane is particularly important in a cold environment. A cold environment tends to compress membranes composed largely of saturated fatty acids, making them less fluid and more susceptible to rupturing. Many organisms (fish are one example) are capable of adapting to cold environments by changing the proportion of unsaturated fatty acids in their membranes in response to the lowering of the temperature.
In animals, the third factor that keeps the membrane fluid is cholesterol. It lies alongside the phospholipids in the membrane and tends to dampen the effects of temperature on the membrane. Thus, cholesterol functions as a buffer, preventing lower temperatures from inhibiting fluidity and preventing higher temperatures from increasing fluidity too much. Cholesterol extends in both directions the range of temperature in which the membrane is appropriately fluid and, consequently, functional. Cholesterol also serves other functions, such as organizing clusters of transmembrane proteins into lipid rafts.
Key Points
• The membrane is fluid but also fairly rigid and can burst if penetrated or if a cell takes in too much water.
• The mosaic nature of the plasma membrane allows a very fine needle to easily penetrate it without causing it to burst and allows it to self-seal when the needle is extracted.
• If saturated fatty acids are compressed by decreasing temperatures, they press in on each other, making a dense and fairly rigid membrane.
• If unsaturated fatty acids are compressed, the “kinks” in their tails push adjacent phospholipid molecules away, which helps maintain fluidity in the membrane.
• The ratio of saturated and unsaturated fatty acids determines the fluidity in the membrane at cold temperatures.
• Cholesterol functions as a buffer, preventing lower temperatures from inhibiting fluidity and preventing higher temperatures from increasing fluidity.
Key Terms
• phospholipid: Any lipid consisting of a diglyceride combined with a phosphate group and a simple organic molecule such as choline or ethanolamine; they are important constituents of biological membranes
• fluidity: A measure of the extent to which something is fluid. The reciprocal of its viscosity. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/05%3A_Structure_and_Function_of_Plasma_Membranes/5.03%3A_Components_and_Structure_-__Membrane_Fluidity.txt |
Learning Objectives
• Indicate the manner in which various materials cross the cell membrane
Plasma membranes must allow or prevent certain substances from entering or leaving a cell. In other words, plasma membranes are selectively permeable; they allow some substances to pass through, but not others. If they were to lose this selectivity, the cell would no longer be able to sustain itself, and it would be destroyed. Some cells require larger amounts of specific substances than other cells; they must have a way of obtaining these materials from extracellular fluids. This may happen passively, as certain materials move back and forth, or the cell may have special mechanisms that facilitate transport. Some materials are so important to a cell that it spends some of its energy (hydrolyzing adenosine triphosphate (ATP)) to obtain these materials. Red blood cells use some of their energy to do this. All cells spend the majority of their energy to maintain an imbalance of sodium and potassium ions between the interior and exterior of the cell.
The most direct forms of membrane transport are passive. Passive transport is a naturally-occurring phenomenon and does not require the cell to exert any of its energy to accomplish the movement. In passive transport, substances move from an area of higher concentration to an area of lower concentration. A physical space in which there is a range of concentrations of a single substance is said to have a concentration gradient.
The passive forms of transport, diffusion and osmosis, move materials of small molecular weight across membranes. Substances diffuse from areas of high concentration to areas of lower concentration; this process continues until the substance is evenly distributed in a system. In solutions containing more than one substance, each type of molecule diffuses according to its own concentration gradient, independent of the diffusion of other substances. Many factors can affect the rate of diffusion, including, but not limited to, concentration gradient, size of the particles that are diffusing, and temperature of the system.
In living systems, diffusion of substances in and out of cells is mediated by the plasma membrane. Some materials diffuse readily through the membrane, but others are hindered; their passage is made possible by specialized proteins, such as channels and transporters. The chemistry of living things occurs in aqueous solutions; balancing the concentrations of those solutions is an ongoing problem. In living systems, diffusion of some substances would be slow or difficult without membrane proteins that facilitate transport.
Key Points
• Plasma membranes are selectively permeable; if they were to lose this selectivity, the cell would no longer be able to sustain itself.
• In passive transport, substances simply move from an area of higher concentration to an area of lower concentration, which does not require the input of energy.
• Concentration gradient, size of the particles that are diffusing, and temperature of the system affect the rate of diffusion.
• Some materials diffuse readily through the membrane, but others require specialized proteins, such as channels and transporters, to carry them into or out of the cell.
Key Terms
• concentration gradient: A concentration gradient is present when a membrane separates two different concentrations of molecules.
• passive transport: A movement of biochemicals and other atomic or molecular substances across membranes that does not require an input of chemical energy.
• permeable: Of or relating to substance, substrate, membrane or material that absorbs or allows the passage of fluids.
5.05: Passive Transport - Selective Permeability
Learning Objectives
• Describe how membrane permeability, concentration gradient, and molecular properties affect biological diffusion rates.
Selective Permeability
Plasma membranes are asymmetric: the interior of the membrane is not identical to the exterior of the membrane. In fact, there is a considerable difference between the array of phospholipids and proteins between the two leaflets that form a membrane. On the interior of the membrane, some proteins serve to anchor the membrane to fibers of the cytoskeleton. There are peripheral proteins on the exterior of the membrane that bind elements of the extracellular matrix. Carbohydrates, attached to lipids or proteins, are also found on the exterior surface of the plasma membrane. These carbohydrate complexes help the cell bind substances that the cell needs in the extracellular fluid. This adds considerably to the selective nature of plasma membranes.
Recall that plasma membranes are amphiphilic; that is, they have hydrophilic and hydrophobic regions. This characteristic helps the movement of some materials through the membrane and hinders the movement of others. Lipid-soluble material with a low molecular weight can easily slip through the hydrophobic lipid core of the membrane. Substances such as the fat-soluble vitamins A, D, E, and K readily pass through the plasma membranes in the digestive tract and other tissues. Fat-soluble drugs and hormones also gain easy entry into cells and are readily transported into the body’s tissues and organs. Molecules of oxygen and carbon dioxide have no charge and so pass through membranes by simple diffusion.
Polar substances present problems for the membrane. While some polar molecules connect easily with the outside of a cell, they cannot readily pass through the lipid core of the plasma membrane. Additionally, while small ions could easily slip through the spaces in the mosaic of the membrane, their charge prevents them from doing so. Ions such as sodium, potassium, calcium, and chloride must have special means of penetrating plasma membranes. Simple sugars and amino acids also need help with transport across plasma membranes, achieved by various transmembrane proteins (channels).
Diffusion across a semipermeable membrane: This interactive shows that smaller molecules have an easier time making it across a semipermeable membrane. Adjust the pore size so the larger molecules can make it through!
Key Points
• The interior and exterior surfaces of the plasma membrane are not identical, which adds to the selective permeability of the membrane.
• Fat soluble substances are able to pass easily to the hydrophobic interior of the plasma membrane and diffuse into the cell.
• Polar molecules and charged molecules do not diffuse easily through the lipid core of the plasma membrane and must be transported across by proteins, sugars, or amino acids.
Key Terms
• polar: a separation of electric charge leading to a molecule or its chemical groups having an electric dipole
• amphiphilic: Having one surface consisting of hydrophilic amino acids and the opposite surface consisting of hydrophobic (or lipophilic) ones. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/05%3A_Structure_and_Function_of_Plasma_Membranes/5.04%3A_Passive_Transport_-_The_Role_of_Passive_Transport.txt |
Learning Objectives
• Describe diffusion and the factors that affect how materials move across the cell membrane.
Diffusion
Diffusion is a passive process of transport. A single substance tends to move from an area of high concentration to an area of low concentration until the concentration is equal across a space. You are familiar with diffusion of substances through the air. For example, think about someone opening a bottle of ammonia in a room filled with people. The ammonia gas is at its highest concentration in the bottle; its lowest concentration is at the edges of the room. The ammonia vapor will diffuse, or spread away, from the bottle; gradually, more and more people will smell the ammonia as it spreads. Materials move within the cell ‘s cytosol by diffusion, and certain materials move through the plasma membrane by diffusion. Diffusion expends no energy. On the contrary, concentration gradients are a form of potential energy, dissipated as the gradient is eliminated.
Each separate substance in a medium, such as the extracellular fluid, has its own concentration gradient independent of the concentration gradients of other materials. In addition, each substance will diffuse according to that gradient. Within a system, there will be different rates of diffusion of the different substances in the medium.
Factors That Affect Diffusion
Molecules move constantly in a random manner at a rate that depends on their mass, their environment, and the amount of thermal energy they possess, which in turn is a function of temperature. This movement accounts for the diffusion of molecules through whatever medium in which they are localized. A substance will tend to move into any space available to it until it is evenly distributed throughout it. After a substance has diffused completely through a space removing its concentration gradient, molecules will still move around in the space, but there will be no net movement of the number of molecules from one area to another. This lack of a concentration gradient in which there is no net movement of a substance is known as dynamic equilibrium. While diffusion will go forward in the presence of a concentration gradient of a substance, several factors affect the rate of diffusion:
• Extent of the concentration gradient: The greater the difference in concentration, the more rapid the diffusion. The closer the distribution of the material gets to equilibrium, the slower the rate of diffusion becomes.
• Mass of the molecules diffusing: Heavier molecules move more slowly; therefore, they diffuse more slowly. The reverse is true for lighter molecules.
• Temperature: Higher temperatures increase the energy and therefore the movement of the molecules, increasing the rate of diffusion. Lower temperatures decrease the energy of the molecules, thus decreasing the rate of diffusion.
• Solvent density: As the density of a solvent increases, the rate of diffusion decreases. The molecules slow down because they have a more difficult time getting through the denser medium. If the medium is less dense, diffusion increases. Because cells primarily use diffusion to move materials within the cytoplasm, any increase in the cytoplasm’s density will inhibit the movement of the materials. An example of this is a person experiencing dehydration. As the body’s cells lose water, the rate of diffusion decreases in the cytoplasm, and the cells’ functions deteriorate. Neurons tend to be very sensitive to this effect. Dehydration frequently leads to unconsciousness and possibly coma because of the decrease in diffusion rate within the cells.
• Solubility: As discussed earlier, nonpolar or lipid-soluble materials pass through plasma membranes more easily than polar materials, allowing a faster rate of diffusion.
• Surface area and thickness of the plasma membrane: Increased surface area increases the rate of diffusion, whereas a thicker membrane reduces it.
• Distance travelled: The greater the distance that a substance must travel, the slower the rate of diffusion. This places an upper limitation on cell size. A large, spherical cell will die because nutrients or waste cannot reach or leave the center of the cell. Therefore, cells must either be small in size, as in the case of many prokaryotes, or be flattened, as with many single-celled eukaryotes.
A variation of diffusion is the process of filtration. In filtration, material moves according to its concentration gradient through a membrane; sometimes the rate of diffusion is enhanced by pressure, causing the substances to filter more rapidly. This occurs in the kidney where blood pressure forces large amounts of water and accompanying dissolved substances, or solutes, out of the blood and into the renal tubules. The rate of diffusion in this instance is almost totally dependent on pressure. One of the effects of high blood pressure is the appearance of protein in the urine, which is “squeezed through” by the abnormally high pressure.
Key Points
• Substances diffuse according to their concentration gradient; within a system, different substances in the medium will each diffuse at different rates according to their individual gradients.
• After a substance has diffused completely through a space, removing its concentration gradient, molecules will still move around in the space, but there will be no net movement of the number of molecules from one area to another, a state known as dynamic equilibrium.
• Several factors affect the rate of diffusion of a solute including the mass of the solute, the temperature of the environment, the solvent density, and the distance traveled.
Key Terms
• diffusion: The passive movement of a solute across a permeable membrane
• concentration gradient: A concentration gradient is present when a membrane separates two different concentrations of molecules. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/05%3A_Structure_and_Function_of_Plasma_Membranes/5.06%3A_Passive_Transport_-_Diffusion.txt |
Learning Objectives
• Explain why and how passive transport occurs
Facilitated transport is a type of passive transport. Unlike simple diffusion where materials pass through a membrane without the help of proteins, in facilitated transport, also called facilitated diffusion, materials diffuse across the plasma membrane with the help of membrane proteins. A concentration gradient exists that would allow these materials to diffuse into the cell without expending cellular energy. However, these materials are ions or polar molecules that are repelled by the hydrophobic parts of the cell membrane. Facilitated transport proteins shield these materials from the repulsive force of the membrane, allowing them to diffuse into the cell.
The material being transported is first attached to protein or glycoprotein receptors on the exterior surface of the plasma membrane. This allows the material that is needed by the cell to be removed from the extracellular fluid. The substances are then passed to specific integral proteins that facilitate their passage. Some of these integral proteins are collections of beta-pleated sheets that form a channel through the phospholipid bilayer. Others are carrier proteins which bind with the substance and aid its diffusion through the membrane.
Channels
The integral proteins involved in facilitated transport are collectively referred to as transport proteins; they function as either channels for the material or carriers. In both cases, they are transmembrane proteins. Channels are specific for the substance that is being transported. Channel proteins have hydrophilic domains exposed to the intracellular and extracellular fluids; they additionally have a hydrophilic channel through their core that provides a hydrated opening through the membrane layers. Passage through the channel allows polar compounds to avoid the nonpolar central layer of the plasma membrane that would otherwise slow or prevent their entry into the cell. Aquaporins are channel proteins that allow water to pass through the membrane at a very high rate.
Channel proteins are either open at all times or they are “gated,” which controls the opening of the channel. The attachment of a particular ion to the channel protein may control the opening or other mechanisms or substances may be involved. In some tissues, sodium and chloride ions pass freely through open channels, whereas in other tissues, a gate must be opened to allow passage. An example of this occurs in the kidney, where both forms of channels are found in different parts of the renal tubules. Cells involved in the transmission of electrical impulses, such as nerve and muscle cells, have gated channels for sodium, potassium, and calcium in their membranes. Opening and closing of these channels changes the relative concentrations on opposing sides of the membrane of these ions, resulting in the facilitation of electrical transmission along membranes (in the case of nerve cells) or in muscle contraction (in the case of muscle cells).
Carrier Proteins
Another type of protein embedded in the plasma membrane is a carrier protein. This protein binds a substance and, in doing so, triggers a change of its own shape, moving the bound molecule from the outside of the cell to its interior; depending on the gradient, the material may move in the opposite direction. Carrier proteins are typically specific for a single substance. This adds to the overall selectivity of the plasma membrane. The exact mechanism for the change of shape is poorly understood. Proteins can change shape when their hydrogen bonds are affected, but this may not fully explain this mechanism. Each carrier protein is specific to one substance, and there are a finite number of these proteins in any membrane. This can cause problems in transporting enough of the material for the cell to function properly.
An example of this process occurs in the kidney. Glucose, water, salts, ions, and amino acids needed by the body are filtered in one part of the kidney. This filtrate, which includes glucose, is then reabsorbed in another part of the kidney. Because there are only a finite number of carrier proteins for glucose, if more glucose is present than the proteins can handle, the excess is not transported; it is excreted from the body in the urine. In a diabetic individual, this is described as “spilling glucose into the urine.” A different group of carrier proteins called glucose transport proteins, or GLUTs, are involved in transporting glucose and other hexose sugars through plasma membranes within the body.
Channel and carrier proteins transport material at different rates. Channel proteins transport much more quickly than do carrier proteins. Channel proteins facilitate diffusion at a rate of tens of millions of molecules per second, whereas carrier proteins work at a rate of a thousand to a million molecules per second.
Key Points
• A concentration gradient exists that would allow ions and polar molecules to diffuse into the cell, but these materials are repelled by the hydrophobic parts of the cell membrane.
• Facilitated diffusion uses integral membrane proteins to move polar or charged substances across the hydrophobic regions of the membrane.
• Channel proteins can aid in the facilitated diffusion of substances by forming a hydrophilic passage through the plasma membrane through which polar and charged substances can pass.
• Channel proteins can be open at all times, constantly allowing a particular substance into or out of the cell, depending on the concentration gradient; or they can be gated and can only be opened by a particular biological signal.
• Carrier proteins aid in facilitated diffusion by binding a particular substance, then altering their shape to bring that substance into or out of the cell.
Key Terms
• facilitated diffusion: The spontaneous passage of molecules or ions across a biological membrane passing through specific transmembrane integral proteins.
• membrane protein: Proteins that are attached to, or associated with the membrane of a cell or an organelle. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/05%3A_Structure_and_Function_of_Plasma_Membranes/5.07%3A_Passive_Transport_-__Facilitated_Transport.txt |
Learning Objectives
• Describe the process of osmosis and explain how concentration gradient affects osmosis
Osmosis and Semipermeable Membranes
Osmosis is the movement of water through a semipermeable membrane according to the concentration gradient of water across the membrane, which is inversely proportional to the concentration of solutes. Semipermeable membranes, also termed selectively permeable membranes or partially permeable membranes, allow certain molecules or ions to pass through by diffusion.
While diffusion transports materials across membranes and within cells, osmosis transports only water across a membrane. The semipermeable membrane limits the diffusion of solutes in the water. Not surprisingly, the aquaporin proteins that facilitate water movement play a large role in osmosis, most prominently in red blood cells and the membranes of kidney tubules.
Mechanism of Osmosis
Osmosis is a special case of diffusion. Water, like other substances, moves from an area of high concentration to one of low concentration. An obvious question is what makes water move at all? Imagine a beaker with a semipermeable membrane separating the two sides or halves. On both sides of the membrane the water level is the same, but there are different concentrations of a dissolved substance, or solute, that cannot cross the membrane (otherwise the concentrations on each side would be balanced by the solute crossing the membrane). If the volume of the solution on both sides of the membrane is the same but the concentrations of solute are different, then there are different amounts of water, the solvent, on either side of the membrane. If there is more solute in one area, then there is less water; if there is less solute in one area, then there must be more water.
To illustrate this, imagine two full glasses of water. One has a single teaspoon of sugar in it, whereas the second one contains one-quarter cup of sugar. If the total volume of the solutions in both cups is the same, which cup contains more water? Because the large amount of sugar in the second cup takes up much more space than the teaspoon of sugar in the first cup, the first cup has more water in it.
Returning to the beaker example, recall that it has a mixture of solutes on either side of the membrane. A principle of diffusion is that the molecules move around and will spread evenly throughout the medium if they can. However, only the material capable of passing through the membrane will diffuse through it. In this example, the solute cannot diffuse through the membrane, but the water can. Water has a concentration gradient in this system. Thus, water will diffuse down its concentration gradient, crossing the membrane to the side where it is less concentrated. This diffusion of water through the membrane—osmosis—will continue until the concentration gradient of water goes to zero or until the hydrostatic pressure of the water balances the osmotic pressure. In the beaker example, this means that the level of fluid in the side with a higher solute concentration will go up.
Key Points
• Osmosis occurs according to the concentration gradient of water across the membrane, which is inversely proportional to the concentration of solutes.
• Osmosis occurs until the concentration gradient of water goes to zero or until the hydrostatic pressure of the water balances the osmotic pressure.
• Osmosis occurs when there is a concentration gradient of a solute within a solution, but the membrane does not allow diffusion of the solute.
Key Terms
• solute: Any substance that is dissolved in a liquid solvent to create a solution
• osmosis: The net movement of solvent molecules from a region of high solvent potential to a region of lower solvent potential through a partially permeable membrane
• semipermeable membrane: A type of biological membrane that will allow certain molecules or ions to pass through it by diffusion and occasionally by specialized facilitated diffusion | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/05%3A_Structure_and_Function_of_Plasma_Membranes/5.08%3A_Passive_Transport_-_Osmosis.txt |
Learning Objectives
• Define tonicity and describe its relevance to osmosis
Tonicity describes how an extracellular solution can change the volume of a cell by affecting osmosis. A solution’s tonicity often directly correlates with the osmolarity of the solution. Osmolarity describes the total solute concentration of the solution. A solution with low osmolarity has a greater number of water molecules relative to the number of solute particles; a solution with high osmolarity has fewer water molecules with respect to solute particles. In a situation in which solutions of two different osmolarities are separated by a membrane permeable to water, though not to the solute, water will move from the side of the membrane with lower osmolarity (and more water) to the side with higher osmolarity (and less water). This effect makes sense if you remember that the solute cannot move across the membrane, and thus the only component in the system that can move—the water—moves along its own concentration gradient. An important distinction that concerns living systems is that osmolarity measures the number of particles (which may be molecules) in a solution. Therefore, a solution that is cloudy with cells may have a lower osmolarity than a solution that is clear if the second solution contains more dissolved molecules than there are cells.
Hypotonic Solutions
Three terms—hypotonic, isotonic, and hypertonic—are used to relate the osmolarity of a cell to the osmolarity of the extracellular fluid that contains the cells. In a hypotonic situation, the extracellular fluid has lower osmolarity than the fluid inside the cell, and water enters the cell. (In living systems, the point of reference is always the cytoplasm, so the prefix hypo- means that the extracellular fluid has a lower concentration of solutes, or a lower osmolarity, than the cell cytoplasm. ) It also means that the extracellular fluid has a higher concentration of water in the solution than does the cell. In this situation, water will follow its concentration gradient and enter the cell, causing the cell to expand.
Hypertonic Solutions
As for a hypertonic solution, the prefix hyper- refers to the extracellular fluid having a higher osmolarity than the cell’s cytoplasm; therefore, the fluid contains less water than the cell does. Because the cell has a relatively higher concentration of water, water will leave the cell, and the cell will shrink.
Isotonic Solutions
In an isotonic solution, the extracellular fluid has the same osmolarity as the cell. If the osmolarity of the cell matches that of the extracellular fluid, there will be no net movement of water into or out of the cell, although water will still move in and out.
Blood cells and plant cells in hypertonic, isotonic, and hypotonic solutions take on characteristic appearances. Cells in an isotonic solution retain their shape. Cells in a hypotonic solution swell as water enters the cell, and may burst if the concentration gradient is large enough between the inside and outside of the cell. Cells in a hypertonic solution shrink as water exits the cell, becoming shriveled.
Key Points
• Osmolarity describes the total solute concentration of a solution; solutions with a low solute concentration have a low osmolarity, while those with a high osmolarity have a high solute concentration.
• Water moves from the side of the membrane with lower osmolarity (and more water) to the side with higher osmolarity (and less water).
• In a hypotonic solution, the extracellular fluid has a lower osmolarity than the fluid inside the cell; water enters the cell.
• In a hypertonic solution, the extracellular fluid has a higher osmolarity than the fluid inside the cell; water leaves the cell.
• In an isotonic solution, the extracellular fluid has the same osmolarity as the cell; there will be no net movement of water into or out of the cell.
Key Terms
• osmolarity: The osmotic concentration of a solution, normally expressed as osmoles of solute per litre of solution.
• hypotonic: Having a lower osmotic pressure than another; a cell in this environment causes water to enter the cell, causing it to swell.
• hypertonic: having a greater osmotic pressure than another
• isotonic: having the same osmotic pressure | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/05%3A_Structure_and_Function_of_Plasma_Membranes/5.09%3A_Passive_Transport_-_Tonicity.txt |
Learning Objectives
• Define an electrochemical gradient and describe how a cell moves substances against this gradient
Electrochemical Gradients
Simple concentration gradients are differential concentrations of a substance across a space or a membrane, but in living systems, gradients are more complex. Because ions move into and out of cells and because cells contain proteins that do not move across the membrane and are mostly negatively charged, there is also an electrical gradient, a difference of charge, across the plasma membrane. The interior of living cells is electrically negative with respect to the extracellular fluid in which they are bathed. At the same time, cells have higher concentrations of potassium (K+) and lower concentrations of sodium (Na+) than does the extracellular fluid. In a living cell, the concentration gradient of Na+ tends to drive it into the cell, and the electrical gradient of Na+ (a positive ion) also tends to drive it inward to the negatively-charged interior. The situation is more complex, however, for other elements such as potassium. The electrical gradient of K+, a positive ion, also tends to drive it into the cell, but the concentration gradient of K+ tends to drive K+ out of the cell. The combined gradient of concentration and electrical charge that affects an ion is called its electrochemical gradient.
Moving Against a Gradient
To move substances against a concentration or electrochemical gradient, the cell must use energy. This energy is harvested from adenosine triphosphate (ATP) generated through the cell’s metabolism. Active transport mechanisms, collectively called pumps, work against electrochemical gradients. Small substances constantly pass through plasma membranes. Active transport maintains concentrations of ions and other substances needed by living cells in the face of these passive movements. Much of a cell’s supply of metabolic energy may be spent maintaining these processes. For example, most of a red blood cell’s metabolic energy is used to maintain the imbalance between exterior and interior sodium and potassium levels required by the cell. Because active transport mechanisms depend on a cell’s metabolism for energy, they are sensitive to many metabolic poisons that interfere with the supply of ATP.
Two mechanisms exist for the transport of small-molecular weight material and small molecules. Primary active transport moves ions across a membrane and creates a difference in charge across that membrane, which is directly dependent on ATP. Secondary active transport describes the movement of material that is due to the electrochemical gradient established by primary active transport that does not directly require ATP.
Carrier Proteins for Active Transport
An important membrane adaption for active transport is the presence of specific carrier proteins or pumps to facilitate movement. There are three types of these proteins or transporters: uniporters, symporters, and antiporters. A uniporter carries one specific ion or molecule. A symporter carries two different ions or molecules, both in the same direction. An antiporter also carries two different ions or molecules, but in different directions. All of these transporters can also transport small, uncharged organic molecules like glucose. These three types of carrier proteins are also found in facilitated diffusion, but they do not require ATP to work in that process. Some examples of pumps for active transport are Na+-K+ ATPase, which carries sodium and potassium ions, and H+-K+ ATPase, which carries hydrogen and potassium ions. Both of these are antiporter carrier proteins. Two other carrier protein pumps are Ca2+ ATPase and H+ATPase, which carry only calcium and only hydrogen ions, respectively.
Key Points
• The electrical and concentration gradients of a membrane tend to drive sodium into and potassium out of the cell, and active transport works against these gradients.
• To move substances against a concentration or electrochemical gradient, the cell must utilize energy in the form of ATP during active transport.
• Primary active transport, which is directly dependent on ATP, moves ions across a membrane and creates a difference in charge across that membrane.
• Secondary active transport, created by primary active transport, is the transport of a solute in the direction of its electrochemical gradient and does not directly require ATP.
• Carrier proteins such as uniporters, symporters, and antiporters perform primary active transport and facilitate the movement of solutes across the cell’s membrane.
Key Terms
• adenosine triphosphate: a multifunctional nucleoside triphosphate used in cells as a coenzyme, often called the “molecular unit of energy currency” in intracellular energy transfer
• active transport: movement of a substance across a cell membrane against its concentration gradient (from low to high concentration) facilitated by ATP conversion
• electrochemical gradient: The difference in charge and chemical concentration across a membrane. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/05%3A_Structure_and_Function_of_Plasma_Membranes/5.10%3A_Active_Transport_-_Electrochemical_Gradient.txt |
Learning Objectives
• Describe how a cell moves sodium and potassium out of and into the cell against its electrochemical gradient
Primary Active Transport
The primary active transport that functions with the active transport of sodium and potassium allows secondary active transport to occur. The secondary transport method is still considered active because it depends on the use of energy as does primary transport.
One of the most important pumps in animals cells is the sodium-potassium pump ( Na+-K+ ATPase ), which maintains the electrochemical gradient (and the correct concentrations of Na+ and K+) in living cells. The sodium-potassium pump moves two K+ into the cell while moving three Na+ out of the cell. The Na+-K+ ATPase exists in two forms, depending on its orientation to the interior or exterior of the cell and its affinity for either sodium or potassium ions. The process consists of the following six steps:
• With the enzyme oriented towards the interior of the cell, the carrier has a high affinity for sodium ions. Three sodium ions bind to the protein.
• ATP is hydrolyzed by the protein carrier, and a low-energy phosphate group attaches to it.
• As a result, the carrier changes shape and re-orients itself towards the exterior of the membrane. The protein’s affinity for sodium decreases, and the three sodium ions leave the carrier.
• The shape change increases the carrier’s affinity for potassium ions, and two such ions attach to the protein. Subsequently, the low-energy phosphate group detaches from the carrier.
• With the phosphate group removed and potassium ions attached, the carrier protein repositions itself towards the interior of the cell.
• The carrier protein, in its new configuration, has a decreased affinity for potassium, and the two ions are released into the cytoplasm. The protein now has a higher affinity for sodium ions, and the process starts again.
Several things have happened as a result of this process. At this point, there are more sodium ions outside of the cell than inside and more potassium ions inside than out. For every three ions of sodium that move out, two ions of potassium move in. This results in the interior being slightly more negative relative to the exterior. This difference in charge is important in creating the conditions necessary for the secondary process. The sodium-potassium pump is, therefore, an electrogenic pump (a pump that creates a charge imbalance), creating an electrical imbalance across the membrane and contributing to the membrane potential.
Key Points
• The sodium-potassium pump moves K+ into the cell while moving Na+ at a ratio of three Na+ for every two K+ ions.
• When the sodium-potassium- ATPase enzyme points into the cell, it has a high affinity for sodium ions and binds three of them, hydrolyzing ATP and changing shape.
• As the enzyme changes shape, it reorients itself towards the outside of the cell, and the three sodium ions are released.
• The enzyme’s new shape allows two potassium to bind and the phosphate group to detach, and the carrier protein repositions itself towards the interior of the cell.
• The enzyme changes shape again, releasing the potassium ions into the cell.
• After potassium is released into the cell, the enzyme binds three sodium ions, which starts the process over again.
Key Terms
• electrogenic pump: An ion pump that generates a net charge flow as a result of its activity.
• Na+-K+ ATPase: An enzyme located in the plasma membrane of all animal cells that pumps sodium out of cells while pumping potassium into cells.
5.12: Active Transport - Secondary Active Transport
Learning Objectives
• Differentiate between primary and secondary active transport
Secondary Active Transport (Co-transport)
Unlike in primary active transport, in secondary active transport, ATP is not directly coupled to the molecule of interest. Instead, another molecule is moved up its concentration gradient, which generates an electrochemical gradient. The molecule of interest is then transported down the electrochemical gradient. While this process still consumes ATP to generate that gradient, the energy is not directly used to move the molecule across the membrane, hence it is known as secondary active transport. Both antiporters and symporters are used in secondary active transport. Co-transporters can be classified as symporters and antiporters depending on whether the substances move in the same or opposite directions across the cell membrane.
Secondary active transport brings sodium ions, and possibly other compounds, into the cell. As sodium ion concentrations build outside the plasma membrane because of the action of the primary active transport process, an electrochemical gradient is created. If a channel protein exists and is open, the sodium ions will be pulled through the membrane. This movement is used to transport other substances that can attach themselves to the transport protein through the membrane. Many amino acids, as well as glucose, enter a cell this way. This secondary process is also used to store high-energy hydrogen ions in the mitochondria of plant and animal cells for the production of ATP. The potential energy that accumulates in the stored hydrogen ions is translated into kinetic energy as the ions surge through the channel protein ATP synthase, and that energy is used to convert ADP into ATP.
Key Points
• While secondary active transport consumes ATP to generate the gradient down which a molecule is moved, the energy is not directly used to move the molecule across the membrane.
• Both antiporters and symporters are used in secondary active transport.
• Secondary active transport brings sodium ions into the cell, and as sodium ion concentrations build outside the plasma membrane, an electrochemical gradient is created.
• If a channel protein is open via primary active transport, the ions will be pulled through the membrane along with other substances that can attach themselves to the transport protein through the membrane.
• Secondary active transport is used to store high-energy hydrogen ions in the mitochondria of plant and animal cells for the production of ATP.
• The potential energy in the hydrogen ions is translated into kinetic energy as the ions surge through the channel protein ATP synthase, and that energy is used to convert ADP into ATP.
Key Terms
• secondary active transport: A method of transport in which the electrochemical potential difference created by pumping ions out of the cell is used to transport molecules across a membrane. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/05%3A_Structure_and_Function_of_Plasma_Membranes/5.11%3A_Active_Transport_-_Primary_Active_Transport.txt |
Learning Objectives
• Describe endocytosis, including phagocytosis, pinocytosis, and receptor-mediated endocytosis.
Endocytosis is a type of active transport that moves particles, such as large molecules, parts of cells, and even whole cells, into a cell. There are different variations of endocytosis, but all share a common characteristic: the plasma membrane of the cell invaginates, forming a pocket around the target particle. The pocket pinches off, resulting in the particle being contained in a newly-created intracellular vesicle formed from the plasma membrane.
Phagocytosis
Phagocytosis (the condition of “cell eating”) is the process by which large particles, such as cells or relatively large particles, are taken in by a cell. For example, when microorganisms invade the human body, a type of white blood cell called a neutrophil will remove the invaders through this process, surrounding and engulfing the microorganism, which is then destroyed by the neutrophil.
In preparation for phagocytosis, a portion of the inward-facing surface of the plasma membrane becomes coated with a protein called clathrin, which stabilizes this section of the membrane. The coated portion of the membrane then extends from the body of the cell and surrounds the particle, eventually enclosing it. Once the vesicle containing the particle is enclosed within the cell, the clathrin disengages from the membrane and the vesicle merges with a lysosome for the breakdown of the material in the newly-formed compartment ( endosome ). When accessible nutrients from the degradation of the vesicular contents have been extracted, the newly-formed endosome merges with the plasma membrane and releases its contents into the extracellular fluid. The endosomal membrane again becomes part of the plasma membrane.
Pinocytosis
A variation of endocytosis is called pinocytosis. This literally means “cell drinking” and was named at a time when the assumption was that the cell was purposefully taking in extracellular fluid. In reality, this is a process that takes in molecules, including water, which the cell needs from the extracellular fluid. Pinocytosis results in a much smaller vesicle than does phagocytosis, and the vesicle does not need to merge with a lysosome.
Potocytosis, a variant of pinocytosis, is a process that uses a coating protein, called caveolin, on the cytoplasmic side of the plasma membrane, which performs a similar function to clathrin. The cavities in the plasma membrane that form the vacuoles have membrane receptors and lipid rafts in addition to caveolin. The vacuoles or vesicles formed in caveolae (singular caveola) are smaller than those in pinocytosis. Potocytosis is used to bring small molecules into the cell and to transport these molecules through the cell for their release on the other side of the cell, a process called transcytosis.
Receptor-mediated Endocytosis
A targeted variation of endocytosis, known as receptor-mediated endocytosis, employs receptor proteins in the plasma membrane that have a specific binding affinity for certain substances. In receptor-mediated endocytosis, as in phagocytosis, clathrin is attached to the cytoplasmic side of the plasma membrane. If uptake of a compound is dependent on receptor-mediated endocytosis and the process is ineffective, the material will not be removed from the tissue fluids or blood. Instead, it will stay in those fluids and increase in concentration. Some human diseases are caused by the failure of receptor-mediated endocytosis. For example, the form of cholesterol termed low-density lipoprotein or LDL (also referred to as “bad” cholesterol) is removed from the blood by receptor-mediated endocytosis. In the human genetic disease familial hypercholesterolemia, the LDL receptors are defective or missing entirely. People with this condition have life-threatening levels of cholesterol in their blood, because their cells cannot clear LDL particles from their blood.
Although receptor-mediated endocytosis is designed to bring specific substances that are normally found in the extracellular fluid into the cell, other substances may gain entry into the cell at the same site. Flu viruses, diphtheria, and cholera toxin all have sites that cross-react with normal receptor-binding sites and gain entry into cells.
Key Points
• Endocytosis consists of phagocytosis, pinocytosis, and receptor -mediated endocytosis.
• Endocytosis takes particles into the cell that are too large to passively cross the cell membrane.
• Phagocytosis is the taking in of large food particles, while pinocytosis takes in liquid particles.
• Receptor-mediated endocytosis uses special receptor proteins to help carry large particles across the cell membrane.
Key Terms
• endosome: An endocytic vacuole through which molecules internalized during endocytosis pass en route to lysosomes
• neutrophil: A cell, especially a white blood cell that consumes foreign invaders in the blood.
5.14: Bulk Transport - Exocytosis
Learning Objectives
• Describe exocytosis and the processes used to release materials from the cell.
Exocytosis’ main purpose is to expel material from the cell into the extracellular fluid; this is the opposite of what occurs in endocytosis. In exocytosis, waste material is enveloped in a membrane and fuses with the interior of the plasma membrane. This fusion opens the membranous envelope on the exterior of the cell and the waste material is expelled into the extracellular space. Exocytosis is used continuously by plant and animal cells to excrete waste from the cells.
Exocytosis is composed of five main stages. The first stage is called vesicle trafficking. This involves the steps required to move, over a significant distance, the vesicle containing the material that is to be disposed. The next stage that occurs is vesicle tethering, which links the vesicle to the cell membrane by biological material at half the diameter of a vesicle. Next, the vesicle’s membrane and the cell membrane connect and are held together in the vesicle docking step. This stage of exocytosis is then followed by vesicle priming, which includes all of the molecular rearrangements and protein and lipid modifications that take place after initial docking. In some cells, there is no priming. The final stage, vesicle fusion, involves the merging of the vesicle membrane with the target membrane. This results in the release of the unwanted materials into the space outside the cell.
Some examples of cells releasing molecules via exocytosis include the secretion of proteins of the extracellular matrix and secretion of neurotransmitters into the synaptic cleft by synaptic vesicles. Some examples of cells using exocytosis include: the secretion of proteins like enzymes, peptide hormones and antibodies from different cells, the flipping of the plasma membrane, the placement of integral membrane proteins(IMPs) or proteins that are attached biologically to the cell, and the recycling of plasma membrane bound receptors (molecules on the cell membrane that intercept signals).
Key Points
• Exocytosis is the opposite of endocytosis as it involves releasing materials from the cell.
• Exocytosis has five stages, each leading up to the vesicle binding with the cell membrane.
• Many bodily functions include the use of exocytosis, such as the release of neurotransmitters into the synaptic cleft and the release of enzymes into the blood.
Key Terms
• secretion: The act of secreting (producing and discharging) a substance, especially from a gland.
• vesicle: A membrane-bound compartment found in a cell.
membrane that intercept signals). | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/05%3A_Structure_and_Function_of_Plasma_Membranes/5.13%3A_Bulk_Transport_-_Endocytosis.txt |
Thumbnail: Metabolic Metro Map. (CC BY-SA 4.0; Chakazul).
06: Metabolism
Learning Objectives
• Explain the importance of metabolism
Energy and Metabolism
All living organisms need energy to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is the set of life-sustaining chemical processes that enables organisms transform the chemical energy stored in molecules into energy that can be used for cellular processes. Animals consume food to replenish energy; their metabolism breaks down the carbohydrates, lipids, proteins, and nucleic acids to provide chemical energy for these processes. Plants convert light energy from the sun into chemical energy stored in molecules during the process of photosynthesis.
Bioenergetics and Chemical Reactions
Scientists use the term bioenergetics to discuss the concept of energy flow through living systems such as cells. Cellular processes such as the building and breaking down of complex molecules occur through step-by-step chemical reactions. Some of these chemical reactions are spontaneous and release energy, whereas others require energy to proceed. All of the chemical reactions that take place inside cells, including those that use energy and those that release energy, are the cell’s metabolism.
Cellular Metabolism
Every task performed by living organisms requires energy. Energy is needed to perform heavy labor and exercise, but humans also use a great deal of energy while thinking and even while sleeping. For every action that requires energy, many chemical reactions take place to provide chemical energy to the systems of the body, including muscles, nerves, heart, lungs, and brain.
The living cells of every organism constantly use energy to survive and grow. Cells break down complex carbohydrates into simple sugars that the cell can use for energy. Muscle cells may consumer energy to build long muscle proteins from small amino acid molecules. Molecules can be modified and transported around the cell or may be distributed to the entire organism. Just as energy is required to both build and demolish a building, energy is required for both the synthesis and breakdown of molecules.
Many cellular process require a steady supply of energy provided by the cell’s metabolism. Signaling molecules such as hormones and neurotransmitters must be synthesized and then transported between cells. Pathogenic bacteria and viruses are ingested and broken down by cells. Cells must also export waste and toxins to stay healthy, and many cells must swim or move surrounding materials via the beating motion of cellular appendages like cilia and flagella.
Key Points
• All living organisms need energy to grow and reproduce, maintain their structures, and respond to their environments; metabolism is the set of the processes that makes energy available for cellular processes.
• Metabolism is a combination of chemical reactions that are spontaneous and release energy and chemical reactions that are non-spontaneous and require energy in order to proceed.
• Living organisms must take in energy via food, nutrients, or sunlight in order to carry out cellular processes.
• The transport, synthesis, and breakdown of nutrients and molecules in a cell require the use of energy.
Key Terms
• metabolism: the complete set of chemical reactions that occur in living cells
• bioenergetics: the study of the energy transformations that take place in living organisms
• energy: the capacity to do work | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/06%3A_Metabolism/6.01%3A_Energy_and_Metabolism_-_The_Role_of_Energy_and_Metabolism.txt |
Learning Objectives
• Differentiate between types of energy
Energy is a property of objects which can be transferred to other objects or converted into different forms, but cannot be created or destroyed. Organisms use energy to survive, grow, respond to stimuli, reproduce, and for every type of biological process. The potential energy stored in molecules can be converted to chemical energy, which can ultimately be converted to kinetic energy, enabling an organism to move. Eventually, most of energy used by organisms is transformed into heat and dissipated.
Kinetic Energy
Energy associated with objects in motion is called kinetic energy. For example, when an airplane is in flight, the airplane is moving through air very quickly—doing work to enact change on its surroundings. The jet engines are converting potential energy in fuel to the kinetic energy of movement. A wrecking ball can perform a large amount of damage, even when moving slowly. However, a still wrecking ball cannot perform any work and therefore has no kinetic energy. A speeding bullet, a walking person, the rapid movement of molecules in the air that produces heat, and electromagnetic radiation, such as sunlight, all have kinetic energy.
Potential Energy
What if that same motionless wrecking ball is lifted two stories above a car with a crane? If the suspended wrecking ball is not moving, is there energy associated with it? Yes, the wrecking ball has energy because the wrecking ball has the potential to do work. This form of energy is called potential energy because it is possible for that object to do work in a given state.
Objects transfer their energy between potential and kinetic states. As the wrecking ball hangs motionlessly, it has 0%0% kinetic and 100%100%potential energy. Once the ball is released, its kinetic energy increases as the ball picks up speed. At the same time, the ball loses potential energy as it nears the ground. Other examples of potential energy include the energy of water held behind a dam or a person about to skydive out of an airplane.
Chemical Energy
Potential energy is not only associated with the location of matter, but also with the structure of matter. A spring on the ground has potential energy if it is compressed, as does a rubber band that is pulled taut. The same principle applies to molecules. On a chemical level, the bonds that hold the atoms of molecules together have potential energy. This type of potential energy is called chemical energy, and like all potential energy, it can be used to do work.
For example, chemical energy is contained in the gasoline molecules that are used to power cars. When gas ignites in the engine, the bonds within its molecules are broken, and the energy released is used to drive the pistons. The potential energy stored within chemical bonds can be harnessed to perform work for biological processes. Different metabolic processes break down organic molecules to release the energy for an organism to grow and survive.
Key Points
• All organisms use different forms of energy to power the biological processes that allow them to grow and survive.
• Kinetic energy is the energy associated with objects in motion.
• Potential energy is the type of energy associated with an object’s potential to do work.
• Chemical energy is the type of energy released from the breakdown of chemical bonds and can be harnessed for metabolic processes.
Key Terms
• chemical energy: The net potential energy liberated or absorbed during the course of a chemical reaction.
• potential energy: Energy possessed by an object because of its position (in a gravitational or electric field), or its condition (as a stretched or compressed spring, as a chemical reactant, or by having rest mass).
• kinetic energy: The energy possessed by an object because of its motion, equal to one half the mass of the body times the square of its velocity. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/06%3A_Metabolism/6.02%3A__Energy_and_Metabolism_-_Types_of_Energy.txt |
Learning Objectives
• Describe the two major types of metabolic pathways
Metabolic Pathways
The processes of making and breaking down carbohydrate molecules illustrate two types of metabolic pathways. A metabolic pathway is a step-by-step series of interconnected biochemical reactions that convert a substrate molecule or molecules through a series of metabolic intermediates, eventually yielding a final product or products. For example, one metabolic pathway for carbohydrates breaks large molecules down into glucose. Another metabolic pathway might build glucose into large carbohydrate molecules for storage. The first of these processes requires energy and is referred to as anabolic. The second process produces energy and is referred to as catabolic. Consequently, metabolism is composed of these two opposite pathways:
1. Anabolism (building molecules)
2. Catabolism (breaking down molecules)
Anabolic Pathways
Anabolic pathways require an input of energy to synthesize complex molecules from simpler ones. One example of an anabolic pathway is the synthesis of sugar from CO2. Other examples include the synthesis of large proteins from amino acid building blocks and the synthesis of new DNA strands from nucleic acid building blocks. These processes are critical to the life of the cell, take place constantly, and demand energy provided by ATP and other high-energy molecules like NADH (nicotinamide adenine dinucleotide) and NADPH.
Catabolic Pathways
Catabolic pathways involve the degradation of complex molecules into simpler ones, releasing the chemical energy stored in the bonds of those molecules. Some catabolic pathways can capture that energy to produce ATP, the molecule used to power all cellular processes. Other energy-storing molecules, such as lipids, are also broken down through similar catabolic reactions to release energy and make ATP.
Importance of Enzymes
Chemical reactions in metabolic pathways rarely take place spontaneously. Each reaction step is facilitated, or catalyzed, by a protein called an enzyme. Enzymes are important for catalyzing all types of biological reactions: those that require energy as well as those that release energy.
Key Points
• A metabolic pathway is a series of chemical reactions in a cell that build and breakdown molecules for cellular processes.
• Anabolic pathways synthesize molecules and require energy.
• Catabolic pathways break down molecules and produce energy.
• Because almost all metabolic reactions take place non-spontaneously, proteins called enzymes help facilitate those chemical reactions.
Key Terms
• catabolism: destructive metabolism, usually including the release of energy and breakdown of materials
• enzyme: a globular protein that catalyses a biological chemical reaction
• anabolism: the constructive metabolism of the body, as distinguished from catabolism
6.04: Energy and Metabolism - Metabolism of Carbohydrates
Learning Objectives
• Analyze the importance of carbohydrate metabolism to energy production
Metabolism of Carbohydrates
Carbohydrates are one of the major forms of energy for animals and plants. Plants build carbohydrates using light energy from the sun (during the process of photosynthesis), while animals eat plants or other animals to obtain carbohydrates. Plants store carbohydrates in long polysaccharides chains called starch, while animals store carbohydrates as the molecule glycogen. These large polysaccharides contain many chemical bonds and therefore store a lot of chemical energy. When these molecules are broken down during metabolism, the energy in the chemical bonds is released and can be harnessed for cellular processes.
Energy Production from Carbohydrates (Cellular Respiration )
The metabolism of any monosaccharide (simple sugar) can produce energy for the cell to use. Excess carbohydrates are stored as starch in plants and as glycogen in animals, ready for metabolism if the energy demands of the organism suddenly increase. When those energy demands increase, carbohydrates are broken down into constituent monosaccharides, which are then distributed to all the living cells of an organism. Glucose (C6H12O6) is a common example of the monosaccharides used for energy production.
Inside the cell, each sugar molecule is broken down through a complex series of chemical reactions. As chemical energy is released from the bonds in the monosaccharide, it is harnessed to synthesize high-energy adenosine triphosphate (ATP) molecules. ATP is the primary energy currency of all cells. Just as the dollar is used as currency to buy goods, cells use molecules of ATP to perform immediate work and power chemical reactions.
The breakdown of glucose during metabolism is call cellular respiration can be described by the equation:
C6H12O6+6O2→6CO2+6H2O+energy
Producing Carbohydrates (Photosynthesis)
Plants and some other types of organisms produce carbohydrates through the process called photosynthesis. During photosynthesis, plants convert light energy into chemical energy by building carbon dioxide gas molecules (CO2) into sugar molecules like glucose. Because this process involves building bonds to synthesize a large molecule, it requires an input of energy (light) to proceed. The synthesis of glucose by photosynthesis is described by this equation (notice that it is the reverse of the previous equation):
6CO2+6H2O+energy→ C6H12O6+6O2
As part of plants’ chemical processes, glucose molecules can be combined with and converted into other types of sugars. In plants, glucose is stored in the form of starch, which can be broken down back into glucose via cellular respiration in order to supply ATP.
Key Points
• The breakdown of glucose living organisms utilize to produce energy is described by the equation: C6H12O6+6O2→6CO2+6H2O+energy.
• The photosynthetic process plants utilize to synthesize glucose is described by the equation:6CO2+6H2O+energy→ C6H12O6+6O2
• Glucose that is consumed is used to make energy in the form of ATP, which is used to perform work and power chemical reactions in the cell.
• During photosynthesis, plants convert light energy into chemical energy that is used to build molecules of glucose.
Key Terms
• adenosine triphosphate: a multifunctional nucleoside triphosphate used in cells as a coenzyme, often called the “molecular unit of energy currency” in intracellular energy transfer
• glucose: a simple monosaccharide (sugar) with a molecular formula of C6H12O6; it is a principal source of energy for cellular metabolism | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/06%3A_Metabolism/6.03%3A__Energy_and_Metabolism_-_Metabolic_Pathways.txt |
Learning Objectives
• Discuss the concept of free energy.
Free Energy
Since chemical reactions release energy when energy-storing bonds are broken, how is the energy associated with chemical reactions quantified and expressed? How can the energy released from one reaction be compared to that of another reaction?
A measurement of free energy is used to quantitate these energy transfers. Free energy is called Gibbs free energy (G) after Josiah Willard Gibbs, the scientist who developed the measurement. Recall that according to the second law of thermodynamics, all energy transfers involve the loss of some amount of energy in an unusable form such as heat, resulting in entropy. Gibbs free energy specifically refers to the energy associated with a chemical reaction that is available after accounting for entropy. In other words, Gibbs free energy is usable energy or energy that is available to do work.
Calculating ∆G
Every chemical reaction involves a change in free energy, called delta G (∆G). The change in free energy can be calculated for any system that undergoes a change, such as a chemical reaction. To calculate ∆G, subtract the amount of energy lost to entropy (denoted as ∆S) from the total energy change of the system. This total energy change in the system is called enthalpy and is denoted as ∆H. The formula for calculating ∆G is as follows, where the symbol T refers to absolute temperature in Kelvin (degrees Celsius + 273): G=ΔH−TΔS.
The standard free energy change of a chemical reaction is expressed as an amount of energy per mole of the reaction product (either in kilojoules or kilocalories, kJ/mol or kcal/mol; 1 kJ = 0.239 kcal) under standard pH, temperature, and pressure conditions. Standard pH, temperature, and pressure conditions are generally calculated at pH 7.0 in biological systems, 25 degrees Celsius, and 100 kilopascals (1 atm pressure), respectively. It is important to note that cellular conditions vary considerably from these standard conditions; therefore, standard calculated ∆G values for biological reactions will be different inside the cell.
Endergonic and Exergonic Reactions
If energy is released during a chemical reaction, then the resulting value from the above equation will be a negative number. In other words, reactions that release energy have a ∆G < 0. A negative ∆G also means that the products of the reaction have less free energy than the reactants because they gave off some free energy during the reaction. Reactions that have a negative ∆G and, consequently, release free energy, are called exergonic reactions. Exergonic means energy is exiting the system. These reactions are also referred to as spontaneous reactions because they can occur without the addition of energy into the system. Understanding which chemical reactions are spontaneous and release free energy is extremely useful for biologists because these reactions can be harnessed to perform work inside the cell. An important distinction must be drawn between the term spontaneous and the idea of a chemical reaction that occurs immediately. Contrary to the everyday use of the term, a spontaneous reaction is not one that suddenly or quickly occurs. The rusting of iron is an example of a spontaneous reaction that occurs slowly, little by little, over time.
If a chemical reaction requires an input of energy rather than releasing energy, then the ∆G for that reaction will be a positive value. In this case, the products have more free energy than the reactants. Thus, the products of these reactions can be thought of as energy-storing molecules. These chemical reactions are called endergonic reactions; they are non-spontaneous. An endergonic reaction will not take place on its own without the addition of free energy.
Free Energy and Biological Processes
In a living cell, chemical reactions are constantly moving towards equilibrium, but never reach it. A living cell is an open system: materials pass in and out, the cell recycles the products of certain chemical reactions into other reactions, and chemical equilibrium is never reached. In this way, living organisms are in a constant energy-requiring, uphill battle against equilibrium and entropy.
When complex molecules, such as starches, are built from simpler molecules, such as sugars, the anabolic process requires energy. Therefore, the chemical reactions involved in anabolic processes are endergonic reactions. On the other hand, the catabolic process of breaking sugar down into simpler molecules releases energy in a series of exergonic reactions. As in the example of rust above, the breakdown of sugar involves spontaneous reactions, but these reactions don’t occur instantaneously. An important concept in the study of metabolism and energy is that of chemical equilibrium. Most chemical reactions are reversible. They can proceed in both directions, releasing energy into their environment in one direction, and absorbing it from the environment in the other direction.
Key Points
• Every chemical reaction involves a change in free energy, called delta G (∆G).
• To calculate ∆G, subtract the amount of energy lost to entropy (∆S) from the total energy change of the system; this total energy change in the system is called enthalpy (∆H ): ΔG=ΔH−TΔS.
• Endergonic reactions require an input of energy; the ∆G for that reaction will be a positive value.
• Exergonic reactions release free energy; the ∆G for that reaction will be a negative value.
Key Terms
• exergonic reaction: A chemical reaction where the change in the Gibbs free energy is negative, indicating a spontaneous reaction
• endergonic reaction: A chemical reaction in which the standard change in free energy is positive, and energy is absorbed
• Gibbs free energy: The difference between the enthalpy of a system and the product of its entropy and absolute temperature | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/06%3A_Metabolism/6.05%3A_Potential_Kinetic_Free_and_Activation_Energy_-_Free_Energy.txt |
Learning Objectives
• Describe the first law of thermodynamics
Thermodynamics is the study of heat energy and other types of energy, such as work, and the various ways energy is transferred within chemical systems. “Thermo-” refers to heat, while “dynamics” refers to motion.
The First Law of Thermodynamics
The first law of thermodynamics deals with the total amount of energy in the universe. The law states that this total amount of energy is constant. In other words, there has always been, and always will be, exactly the same amount of energy in the universe.
Energy exists in many different forms. According to the first law of thermodynamics, energy can be transferred from place to place or changed between different forms, but it cannot be created or destroyed. The transfers and transformations of energy take place around us all the time. For instance, light bulbs transform electrical energy into light energy, and gas stoves transform chemical energy from natural gas into heat energy. Plants perform one of the most biologically useful transformations of energy on Earth: they convert the energy of sunlight into the chemical energy stored within organic molecules.
The System and Surroundings
Thermodynamics often divides the universe into two categories: the system and its surroundings. In chemistry, the system almost always refers to a given chemical reaction and the container in which it takes place. The first law of thermodynamics tells us that energy can neither be created nor destroyed, so we know that the energy that is absorbed in an endothermic chemical reaction must have been lost from the surroundings. Conversely, in an exothermic reaction, the heat that is released in the reaction is given off and absorbed by the surroundings. Stated mathematically, we have:
ΔE=ΔEsys+ΔEsurr=0
Heat and Work
We know that chemical systems can either absorb heat from their surroundings, if the reaction is endothermic, or release heat to their surroundings, if the reaction is exothermic. However, chemical reactions are often used to do work instead of just exchanging heat. For instance, when rocket fuel burns and causes a space shuttle to lift off from the ground, the chemical reaction, by propelling the rocket, is doing work by applying a force over a distance.
If you’ve ever witnessed a video of a space shuttle lifting off, the chemical reaction that occurs also releases tremendous amounts of heat and light. Another useful form of the first law of thermodynamics relates heat and work for the change in energy of the internal system:
ΔEsys=Q+W
While this formulation is more commonly used in physics, it is still important to know for chemistry.
Key Points
• According to the first law of thermodynamics, the total amount of energy in the universe is constant.
• Energy can be transferred from place to place or transformed into different forms, but it cannot be created or destroyed.
• Living organisms have evolved to obtain energy from their surroundings in forms that they can transfer or transform into usable energy to do work.
Key Terms
• first law of thermodynamics: A version of the law of conservation of energy, specialized for thermodynamical systems, that states that the energy of an isolated system is constant and can neither be created nor destroyed.
• work: A measure of energy expended by moving an object, usually considered to be force times distance. No work is done if the object does not move. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/06%3A_Metabolism/6.06%3A_Potential_Kinetic_Free_and_Activation_Energy_-_The_First_Law_of_Thermodynamics.txt |
Learning Objectives
• Explain how living organisms can increase their order despite the second law of thermodynamics
The Second Law of Thermodynamics
A living cell ‘s primary tasks of obtaining, transforming, and using energy to do work may seem simple enough, but they are more problematic than they appear. The second law of thermodynamics explains why: No energy transfers or transformations in the universe are completely efficient. In every energy transfer, some amount of energy is lost in a form that is unusable. In most cases, this energy is in the form of heat. Thermodynamically, heat energy is defined as the energy transferred from one system to another that is not doing work. For example, when an airplane flies through the air, some of the energy of the flying plane is lost as heat energy due to friction with the surrounding air. This friction heats the air by temporarily increasing the speed of air molecules. Likewise, some energy is lost in the form of heat during cellular metabolic reactions. This is good for warm-blooded creatures like us because heat energy helps to maintain our body temperature. Strictly speaking, no energy transfer is completely efficient because some energy is lost in an unusable form.
Entropy
An important concept in physical systems is disorder (also known as randomness). The more energy that is lost by a system to its surroundings, the less ordered and more random the system is. Scientists define the measure of randomness or disorder within a system as entropy. High entropy means high disorder and low energy. To better understand entropy, remember that it requires energy to maintain structure. For example, think about an ice cube. It is made of water molecules bound together in an orderly lattice. This arrangement takes energy to maintain. When the ice cube melts and becomes water, its molecules are more disordered, in a random arrangement as opposed to a structure. Overall, there is less energy in the system inside the molecular bonds. Therefore, water can be said to have greater entropy than ice.
This holds true for solids, liquids, and gases in general. Solids have the highest internal energy holding them together and therefore the lowest entropy. Liquids are more disordered and it takes less energy to hold them together. Therefore they are higher in entropy than solids, but lower than gases, which are so disordered that they have the highest entropy and lowest amount of energy spent holding them together.
Entropy changes also occur in chemical reactions. In an exergonic chemical reaction where energy is released, entropy increases because the final products have less energy inside them holding their chemical bonds together. That energy has been lost to the environment, usually in the form of heat.
All physical systems can be thought of in this way. Living things are highly ordered, requiring constant energy input to be maintained in a state of low entropy. As living systems take in energy-storing molecules and transform them through chemical reactions, they lose some amount of usable energy in the process because no reaction is completely efficient. They also produce waste and by-products that are not useful energy sources. This process increases the entropy of the system’s surroundings. Since all energy transfers result in the loss of some usable energy, the second law of thermodynamics states that every energy transfer or transformation increases the entropy of the universe. Even though living things are highly ordered and maintain a state of low entropy, the entropy of the universe in total is constantly increasing due to the loss of usable energy with each energy transfer that occurs. Essentially, living things are in a continuous uphill battle against this constant increase in universal entropy.
Key Points
• During energy transfer, some amount of energy is lost in the form of unusable heat energy.
• Because energy is lost in an unusable form, no energy transfer is completely efficient.
• The more energy that is lost by a system to its surroundings, the less ordered and more random the system is.
• Entropy is a measure of randomness and disorder; high entropy means high disorder and low energy.
• As chemical reactions reach a state of equilibrium, entropy increases; and as molecules at a high concentration in one place diffuse and spread out, entropy also increases.
Key Terms
• second law of thermodynamics: Every energy transfer or transformation increases the entropy of the universe since all energy transfers result in the loss of some usable energy.
• entropy: A measure of randomness and disorder in a system. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/06%3A_Metabolism/6.07%3A_Potential_Kinetic_Free_and_Activation_Energy_-__The_Second_Law_of_Thermodynamics.txt |
Learning Objectives
• Discuss the concept of activation energy
Many chemical reactions, and almost all biochemical reactions do not occur spontaneously and must have an initial input of energy (called the activation energy) to get started. Activation energy must be considered when analyzing both endergonic and exergonic reactions. Exergonic reactions have a net release of energy, but they still require a small amount of energy input before they can proceed with their energy-releasing steps. This small amount of energy input necessary for all chemical reactions to occur is called the activation energy (or free energy of activation) and is abbreviated EA.
Activation Energy in Chemical Reactions
Why would an energy-releasing, negative ∆G reaction actually require some energy to proceed? The reason lies in the steps that take place during a chemical reaction. During chemical reactions, certain chemical bonds are broken and new ones are formed. For example, when a glucose molecule is broken down, bonds between the carbon atoms of the molecule are broken. Since these are energy-storing bonds, they release energy when broken. However, to get them into a state that allows the bonds to break, the molecule must be somewhat contorted. A small energy input is required to achieve this contorted state, which is called the transition state: it is a high-energy, unstable state. For this reason, reactant molecules don’t last long in their transition state, but very quickly proceed to the next steps of the chemical reaction.
Cells will at times couple an exergonic reaction (ΔG<0) with endergonic reactions (ΔG>0), allowing them to proceed. This spontaneous shift from one reaction to another is called energy coupling. The free energy released from the exergonic reaction is absorbed by the
endergonic reaction. One example of energy coupling using ATP involves a transmembrane ion pump that is extremely important for cellular function.
Free Energy Diagrams
Free energy diagrams illustrate the energy profiles for a given reaction. Whether the reaction is exergonic (ΔG<0) or endergonic (ΔG>0) determines whether the products in the diagram will exist at a lower or higher energy state than the reactants. However, the measure of the activation energy is independent of the reaction’s ΔG. In other words, at a given temperature, the activation energy depends on the nature of the chemical transformation that takes place, but not on the relative energy state of the reactants and products.
Although the image above discusses the concept of activation energy within the context of the exergonic forward reaction, the same principles apply to the reverse reaction, which must be endergonic. Notice that the activation energy for the reverse reaction is larger than for the forward reaction.
Heat Energy
The source of the activation energy needed to push reactions forward is typically heat energy from the surroundings. Heat energy (the total bond energy of reactants or products in a chemical reaction) speeds up the motion of molecules, increasing the frequency and force with which they collide. It also moves atoms and bonds within the molecule slightly, helping them reach their transition state. For this reason, heating up a system will cause chemical reactants within that system to react more frequently. Increasing the pressure on a system has the same effect. Once reactants have absorbed enough heat energy from their surroundings to reach the transition state, the reaction will proceed.
The activation energy of a particular reaction determines the rate at which it will proceed. The higher the activation energy, the slower the chemical reaction will be. The example of iron rusting illustrates an inherently slow reaction. This reaction occurs slowly over time because of its high EA. Additionally, the burning of many fuels, which is strongly exergonic, will take place at a negligible rate unless their activation energy is overcome by sufficient heat from a spark. Once they begin to burn, however, the chemical reactions release enough heat to continue the burning process, supplying the activation energy for surrounding fuel molecules.
Like these reactions outside of cells, the activation energy for most cellular reactions is too high for heat energy to overcome at efficient rates. In other words, in order for important cellular reactions to occur at significant rates (number of reactions per unit time), their activation energies must be lowered; this is referred to as catalysis. This is a very good thing as far as living cells are concerned. Important macromolecules, such as proteins, DNA, and RNA, store considerable energy, and their breakdown is exergonic. If cellular temperatures alone provided enough heat energy for these exergonic reactions to overcome their activation barriers, the essential components of a cell would disintegrate.
The Arrhenius Equation
The Arrhenius equations relates the rate of a chemical reaction to the magnitude of the activation energy:
k=AeEa/RT
where
• k is the reaction rate coefficient or constant
• A is the frequency factor of the reaction. It is determined experimentally.
• R is the Universal Gas constant
• T is the temperature in Kelvin
Key Points
• Reactions require an input of energy to initiate the reaction; this is called the activation energy (EA).
• Activation energy is the amount of energy required to reach the transition state.
• The source of the activation energy needed to push reactions forward is typically heat energy from the surroundings.
• For cellular reactions to occur fast enough over short time scales, their activation energies are lowered by molecules called catalysts.
• Enzymes are catalysts.
Key Terms
• activation energy: The minimum energy required for a reaction to occur.
• catalysis: The increase in the rate of a chemical reaction by lowering its activation energy.
• transition state: An intermediate state during a chemical reaction that has a higher energy than the reactants or the products. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/06%3A_Metabolism/6.08%3A_Potential_Kinetic_Free_and_Activation_Energy_-_Activation_Energy.txt |
Learning Objectives
• Explain the role of ATP as the currency of cellular energy
ATP: Adenosine Triphosphate
Adenosine triphosphate (ATP) is the energy currency for cellular processes. ATP provides the energy for both energy-consuming endergonic reactions and energy-releasing exergonic reactions, which require a small input of activation energy. When the chemical bonds within ATP are broken, energy is released and can be harnessed for cellular work. The more bonds in a molecule, the more potential energy it contains. Because the bond in ATP is so easily broken and reformed, ATP is like a rechargeable battery that powers cellular process ranging from DNA replication to protein synthesis.
Molecular Structure
Adenosine triphosphate (ATP) is comprised of the molecule adenosine bound to three phosphate groups. Adenosine is a nucleoside consisting of the nitrogenous base adenine and the five-carbon sugar ribose. The three phosphate groups, in order of closest to furthest from the ribose sugar, are labeled alpha, beta, and gamma. Together, these chemical groups constitute an energy powerhouse. The two bonds between the phosphates are equal high-energy bonds (phosphoanhydride bonds) that, when broken, release sufficient energy to power a variety of cellular reactions and processes. The bond between the beta and gamma phosphate is considered “high-energy” because when the bond breaks, the products [adenosine diphosphate (ADP) and one inorganic phosphate group (Pi)] have a lower free energy than the reactants (ATP and a water molecule). ATP breakdown into ADP and Pi is called hydrolysis because it consumes a water molecule (hydro-, meaning “water”, and lysis, meaning “separation”).
ATP Hydrolysis and Synthesis
ATP is hydrolyzed into ADP in the following reaction:
ATP+H2O→ADP+Pi+free energy
Like most chemical reactions, the hydrolysis of ATP to ADP is reversible. The reverse reaction combines ADP + Pi to regenerate ATP from ADP. Since ATP hydrolysis releases energy, ATP synthesis must require an input of free energy.
ADP is combined with a phosphate to form ATP in the following reaction:
ADP+Pi+free energy→ATP+H2O
ATP and Energy Coupling
Exactly how much free energy (∆G) is released with the hydrolysis of ATP, and how is that free energy used to do cellular work? The calculated ∆G for the hydrolysis of one mole of ATP into ADP and Pi is −7.3 kcal/mole (−30.5 kJ/mol). However, this is only true under standard conditions, and the ∆G for the hydrolysis of one mole of ATP in a living cell is almost double the value at standard conditions: 14 kcal/mol (−57 kJ/mol).
ATP is a highly unstable molecule. Unless quickly used to perform work, ATP spontaneously dissociates into ADP + Pi, and the free energy released during this process is lost as heat. To harness the energy within the bonds of ATP, cells use a strategy called energy coupling.
Energy Coupling in Sodium-Potassium Pumps
Cells couple the exergonic reaction of ATP hydrolysis with the endergonic reactions of cellular processes. For example, transmembrane ion pumps in nerve cells use the energy from ATP to pump ions across the cell membrane and generate an action potential. The sodium-potassium pump (Na+/K+pump) drives sodium out of the cell and potassium into the cell. When ATP is hydrolyzed, it transfers its gamma phosphate to the pump protein in a process called phosphorylation. The Na+/K+ pump gains the free energy and undergoes a conformational change, allowing it to release three Na+ to the outside of the cell. Two extracellular K+ ions bind to the protein, causing the protein to change shape again and discharge the phosphate. By donating free energy to the Na+/K+ pump, phosphorylation drives the endergonic reaction.
Energy Coupling in Metabolism
During cellular metabolic reactions, or the synthesis and breakdown of nutrients, certain molecules must be altered slightly in their conformation to become substrates for the next step in the reaction series. In the very first steps of cellular respiration, glucose is broken down through the process of glycolysis. ATP is required for the phosphorylation of glucose, creating a high-energy but unstable intermediate. This phosphorylation reaction causes a conformational change that allows enzymes to convert the phosphorylated glucose molecule to the phosphorylated sugar fructose. Fructose is a necessary intermediate for glycolysis to move forward. In this example, the exergonic reaction of ATP hydrolysis is coupled with the endergonic reaction of converting glucose for use in the metabolic pathway.
Key Points
• Adenosine triphosphate is composed of the nitrogenous base adenine, the five-carbon sugar ribose, and three phosphate groups.
• ATP is hydrolyzed to ADP in the reaction ATP+H2O→ADP+Pi+ free energy; the calculated ∆G for the hydrolysis of 1 mole of ATP is -57 kJ/mol.
• ADP is combined with a phosphate to form ATP in the reaction ADP+Pi+free energy→ATP+H2O.
• The energy released from the hydrolysis of ATP into ADP is used to perform cellular work, usually by coupling the exergonic reaction of ATP hydrolysis with endergonic reactions.
• Sodium-potassium pumps use the energy derived from exergonic ATP hydrolysis to pump sodium and potassium ions across the cell membrane while phosphorylation drives the endergonic reaction.
Key Terms
• energy coupling: Energy coupling occurs when the energy produced by one reaction or system is used to drive another reaction or system.
• endergonic: Describing a reaction that absorbs (heat) energy from its environment.
• exergonic: Describing a reaction that releases energy (heat) into its environment.
• free energy: Gibbs free energy is a thermodynamic potential that measures the useful or process-initiating work obtainable from a thermodynamic system at a constant temperature and pressure (isothermal, isobaric).
• hydrolysis: A chemical process of decomposition involving the splitting of a bond by the addition of water. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/06%3A_Metabolism/6.09%3A_ATP_-_Adenosine_Triphosphate.txt |
Learning Objectives
• Describe models of substrate binding to an enzyme’s active site.
Enzyme Active Site and Substrate Specificity
Enzymes bind with chemical reactants called substrates. There may be one or more substrates for each type of enzyme, depending on the particular chemical reaction. In some reactions, a single-reactant substrate is broken down into multiple products. In others, two substrates may come together to create one larger molecule. Two reactants might also enter a reaction, both become modified, and leave the reaction as two products.
The enzyme’s active site binds to the substrate. Since enzymes are proteins, this site is composed of a unique combination of amino acid residues (side chains or R groups). Each amino acid residue can be large or small; weakly acidic or basic; hydrophilic or hydrophobic; and positively-charged, negatively-charged, or neutral. The positions, sequences, structures, and properties of these residues create a very specific chemical environment within the active site. A specific chemical substrate matches this site like a jigsaw puzzle piece and makes the enzyme specific to its substrate.
Active Sites and Environmental Conditions
Environmental conditions can affect an enzyme’s active site and, therefore, the rate at which a chemical reaction can proceed. Increasing the environmental temperature generally increases reaction rates because the molecules are moving more quickly and are more likely to come into contact with each other.
However, increasing or decreasing the temperature outside of an optimal range can affect chemical bonds within the enzyme and change its shape. If the enzyme changes shape, the active site may no longer bind to the appropriate substrate and the rate of reaction will decrease. Dramatic changes to the temperature and pH will eventually cause enzymes to denature.
Induced Fit and Enzyme Function
For many years, scientists thought that enzyme-substrate binding took place in a simple “lock-and-key” fashion. This model asserted that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view called induced fit. As the enzyme and substrate come together, their interaction causes a mild shift in the enzyme’s structure that confirms an ideal binding arrangement between the enzyme and the substrate. This dynamic binding maximizes the enzyme’s ability to catalyze its reaction.
Enzyme-Substrate Complex
When an enzyme binds its substrate, it forms an enzyme-substrate complex. This complex lowers the activation energy of the reaction and promotes its rapid progression by providing certain ions or chemical groups that actually form covalent bonds with molecules as a necessary step of the reaction process. Enzymes also promote chemical reactions by bringing substrates together in an optimal orientation, lining up the atoms and bonds of one molecule with the atoms and bonds of the other molecule. This can contort the substrate molecules and facilitate bond-breaking. The active site of an enzyme also creates an ideal environment, such as a slightly acidic or non-polar environment, for the reaction to occur. The enzyme will always return to its original state at the completion of the reaction. One of the important properties of enzymes is that they remain ultimately unchanged by the reactions they catalyze. After an enzyme is done catalyzing a reaction, it releases its products (substrates).
Key Points
• The enzyme ‘s active site binds to the substrate.
• Increasing the temperature generally increases the rate of a reaction, but dramatic changes in temperature and pH can denature an enzyme, thereby abolishing its action as a catalyst.
• The induced fit model states an substrate binds to an active site and both change shape slightly, creating an ideal fit for catalysis.
• When an enzyme binds its substrate it forms an enzyme-substrate complex.
• Enzymes promote chemical reactions by bringing substrates together in an optimal orientation, thus creating an ideal chemical environment for the reaction to occur.
• The enzyme will always return to its original state at the completion of the reaction.
Key Terms
• substrate: A reactant in a chemical reaction is called a substrate when acted upon by an enzyme.
• induced fit: Proposes that the initial interaction between enzyme and substrate is relatively weak, but that these weak interactions rapidly induce conformational changes in the enzyme that strengthen binding.
• active site: The active site is the part of an enzyme to which substrates bind and where a reaction is catalyzed. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/06%3A_Metabolism/6.10%3A_Enzymes_-_Active_Site_and_Substrate_Specificity.txt |
Learning Objectives
• Explain the effect of an enzyme on chemical equilibrium
Control of Metabolism Through Enzyme Regulation
Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, a stomach cell requires a different amount of energy than a skin cell, fat storage cell, blood cell, or nerve cell. The same stomach cell may also need more energy immediately after a meal and less energy between meals.
A cell’s function is encapsulated by the chemical reactions it can carry out. Enzymes lower the activation energies of chemical reactions; in cells, they promote those reactions that are specific to the cell’s function. Because enzymes ultimately determine which chemical reactions a cell can carry out and the rate at which they can proceed, they are key to cell functionality.
Competitive and Noncompetitive Inhibition
The cell uses specific molecules to regulate enzymes in order to promote or inhibit certain chemical reactions. Sometimes it is necessary to inhibit an enzyme to reduce a reaction rate, and there is more than one way for this inhibition to occur. In competitive inhibition, an inhibitor molecule is similar enough to a substrate that it can bind to the enzyme’s active site to stop it from binding to the substrate. It “competes” with the substrate to bind to the enzyme.
In noncompetitive inhibition, an inhibitor molecule binds to the enzyme at a location other than the active site (an allosteric site). The substrate can still bind to the enzyme, but the inhibitor changes the shape of the enzyme so it is no longer in optimal position to catalyze the reaction.
Allosteric Inhibition and Activation
In noncompetitive allosteric inhibition, inhibitor molecules bind to an enzyme at the allosteric site. Their binding induces a conformational change that reduces the affinity of the enzyme’s active site for its substrate. The binding of this allosteric inhibitor changes the conformation of the enzyme and its active site, so the substrate is not able to bind. This prevents the enzyme from lowering the activation energy of the reaction, and the reaction rate is reduced.
However, allosteric inhibitors are not the only molecules that bind to allosteric sites. Allosteric activators can increase reaction rates. They bind to an allosteric site which induces a conformational change that increases the affinity of the enzyme’s active site for its substrate. This increases the reaction rate.
Cofactors and Coenzymes
Many enzymes only work if bound to non-protein helper molecules called cofactors and coenzymes. Binding to these molecules promotes optimal conformation and function for their respective enzymes. These molecules bind temporarily through ionic or hydrogen bonds or permanently through stronger covalent bonds.
Cofactors are inorganic ions such as iron (Fe2+) and magnesium (Mg2+). For example, DNA polymerase requires a zinc ion (Zn2+) to build DNA molecules. Coenzymes are organic helper molecules with a basic atomic structure made up of carbon and hydrogen. The most common coenzymes are dietary vitamins. Vitamin C is a coenzyme for multiple enzymes that take part in building collagen, an important component of connective tissue. Pyruvate dehydrogenase is a complex of several enzymes that requires one cofactor and five different organic coenzymes to catalyze its chemical reaction. The availability of various cofactors and coenzymes regulates enzyme function.
Enzyme Compartmentalization
In eukaryotic cells, molecules such as enzymes are usually compartmentalized into different organelles. This organization contributes to enzyme regulation because certain cellular processes are contained in separate organelles. For example, the enzymes involved in the later stages of cellular respiration carry out reactions exclusively in the mitochondria. The enzymes involved in the digestion of cellular debris and foreign materials are located within lysosomes.
Feedback Inhibition in Metabolic Pathways
Feedback inhibition is when a reaction product is used to regulate its own further production. Cells have evolved to use feedback inhibition to regulate enzyme activity in metabolism, by using the products of the enzymatic reactions to inhibit further enzyme activity. Metabolic reactions, such as anabolic and catabolic processes, must proceed according to the demands of the cell. In order to maintain chemical equilibrium and meet the needs of the cell, some metabolic products inhibit the enzymes in the chemical pathway while some reactants activate them.
The production of both amino acids and nucleotides is controlled through feedback inhibition. For an example of feedback inhibition, consider ATP. It is the product of the catabolic metabolism of sugar (cellular respiration), but it also acts as an allosteric regulator for the same enzymes that produced it. ATP is an unstable molecule that can spontaneously dissociate into ADP; if too much ATP were present, most of it would go to waste. This feedback inhibition prevents the production of additional ATP if it is already abundant. However, while ATP is an inhibitor, ADP is an allosteric activator. When levels of ADP are high compared to ATP levels, ADP triggers the catabolism of sugar to produce more ATP.
Key Points
• In competitive inhibition, an inhibitor molecule competes with a substrate by binding to the enzyme ‘s active site so the substrate is blocked.
• In noncompetitive inhibition (also known as allosteric inhibition), an inhibitor binds to an allosteric site; the substrate can still bind to the enzyme, but the enzyme is no longer in optimal position to catalyze the reaction.
• Allosteric inhibitors induce a conformational change that changes the shape of the active site and reduces the affinity of the enzyme’s active site for its substrate.
• Allosteric activators induce a conformational change that changes the shape of the active site and increases the affinity of the enzyme’s active site for its substrate.
• Feedback inhibition involves the use of a reaction product to regulate its own further production.
• Inorganic cofactors and organic coenzymes promote optimal enzyme orientation and function.
• Vitamins act as coenzymes (or precursors to coenzymes) and are necessary for enzymes to function.
Key Terms
• coenzyme: An organic molecule that is necessary for an enzyme to function.
• allosteric site: A site other than the active site on an enzyme.
• cofactor: An inorganic molecule that is necessary for an enzyme to function. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/06%3A_Metabolism/6.11%3A_Enzymes_-_Control_of_Metabolism_Through_Enzyme_Regulation.txt |
Cellular respiration is a set of metabolic reactions and processes that take place in the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate (ATP), and then release waste products.
07: Cellular Respiration
Learning Objectives
• Discuss the importance of cellular respiration
Introduction: Cellular Respiration
An electrical energy plant converts energy from one form to another form that can be more easily used. For example, geothermal energy plants start with underground thermal energy (heat) and transform it into electrical energy that will be transported to homes and factories.
Like a generating plant, living organisms must take in energy from their environment and convert it into to a form their cells can use. Organisms ingest large molecules, like carbohydrates, proteins, and fats, and convert them into smaller molecules like carbon dioxide and water. This process is called cellular respiration, a form of catabolism, and makes energy available for the cell to use. The energy released by cellular respiration is temporarily captured by the formation of adenosine triphosphate (ATP) within the cell. ATP is the principle form of stored energy used for cellular functions and is frequently referred to as the energy currency of the cell.
The nutrients broken down through cellular respiration lose electrons throughout the process and are said to be oxidized. When oxygen is used to help drive the oxidation of nutrients the process is called aerobic respiration. Aerobic respiration is common among the eukaryotes, including humans, and takes place mostly within the mitochondria. Respiration occurs within the cytoplasm of prokaryotes. Several prokaryotes and a few eukaryotes use an inorganic molecule other than oxygen to drive the oxidation of their nutrients in a process called anaerobic respiration. Electron acceptors for anaerobic respiration include nitrate, sulfate, carbon dioxide, and several metal ions.
The energy released during cellular respiration is then used in other biological processes. These processes build larger molecules that are essential to an organism’s survival, such as amino acids, DNA, and proteins. Because they synthesize new molecules, these processes are examples of anabolism.
Key Points
• Organisms ingest organic molecules like the carbohydrate glucose to obtain the energy needed for cellular functions.
• The energy in glucose can be extracted in a series of chemical reactions known as cellular respiration.
• Cellular respiration produces energy in the form of ATP, which is the universal energy currency for cells.
Key Terms
• aerobic respiration: the process of converting the biochemical energy in nutrients to ATP in the presence of oxygen
• adenosine triphosphate: a multifunctional nucleoside triphosphate used in cells as a coenzyme, often called the “molecular unit of energy currency” in intracellular energy transfer
• cellular respiration: the set of the metabolic reactions and processes that take place in the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate (ATP)
• catabolism: the breakdown of large molecules into smaller ones usually accompanied by the release of energy
7.02: Energy in Living Systems - Electrons and Energy
Learning Objectives
• Describe the role played by electrons in energy production and storage
Electrons and Energy
The removal of an electron from a molecule via a process called oxidation results in a decrease in the potential energy stored in the oxidized compound. When oxidation occurs in the cell, the electron (sometimes as part of a hydrogen atom) does not remain un-bonded in the cytoplasm. Instead, the electron shifts to a second compound, reducing the second compound (oxidation of one species always occurs in tandem with reduction of another).
The shift of an electron from one compound to another removes some potential energy from the first compound (the oxidized compound) and increases the potential energy of the second compound (the reduced compound). The transfer of electrons between molecules via oxidation and reduction is important because most of the energy stored in atoms is in the form of high-energy electrons; it is this energy that is used to fuel cellular functions. The transfer of energy in the form of electrons allows the cell to transfer and use energy in an incremental fashion: in small packages rather than as a single, destructive burst.
Electron carriers
In living systems, a small class of molecules functions as electron shuttles: they bind and carry high-energy electrons between compounds in cellular pathways. The principal electron carriers we will consider are derived from the vitamin B group, which are derivatives of nucleotides. These compounds can be easily reduced (that is, they accept electrons) or oxidized (they lose electrons). Nicotinamide adenine dinucleotide (NAD) is derived from vitamin B3, niacin. NAD+ is the oxidized form of niacin; NADH is the reduced form after it has accepted two electrons and a proton (which together are the equivalent of a hydrogen atom with an extra electron). It is noteworthy that NAD+must accept two electrons at once; it cannot serve as a one-electron carrier.
NAD+ can accept electrons from an organic molecule according to the general equation:
RH (Reducing agent) + NAD+ (Oxidizing agent) → NADH (Reduced) + R (Oxidized)
When electrons are added to a compound, the compound is reduced. A compound that reduces another is called a reducing agent. In the above equation, RH is a reducing agent and NAD+ is reduced to NADH. When electrons are removed from a compound, the compound is oxidized. In the above equation, NAD+ is an oxidizing agent and RH is oxidized to R. The molecule NADH is critical for cellular respiration and other metabolic pathways.
Similarly, flavin adenine dinucleotide (FAD+) is derived from vitamin B2, also called riboflavin. Its reduced form is FADH2. A second variation of NAD, NADP, contains an extra phosphate group. Both NAD+ and FAD+ are extensively used in energy extraction from sugars, and NADP plays an important role in anabolic reactions and photosynthesis.
Key Points
• When electrons are added to a compound, the compound is reduced; a compound that reduces another is called a reducing agent.
• When electrons are removed from a compound, the compound is considered oxidized; a compound that oxidizes another is called an oxidizing agent.
• The transfer of energy in the form of electrons allows the cell to transfer and use energy in an incremental fashion.
• The principle electron carriers are NAD+ and NADH because they can be easily oxidized and reduced, respectively.
• NAD+ is the oxidized form of the niacin and NADH is the reduced form after it has accepted two electrons and a proton.
Key Terms
• oxidation: A reaction in which the atoms of an element lose electrons and the valence of the element increases.
• reduction: A reaction in which electrons are gained and valence is reduced; often by the removal of oxygen or the addition of hydrogen.
• nicotinamide adenine dinucleotide: (NAD) An organic coenzyme involved in biological oxidation and reduction reactions.
• electron shuttle: molecules that bind and carry high-energy electrons between compounds in cellular pathways | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/07%3A_Cellular_Respiration/7.01%3A_Energy_in_Living_Systems_-_Transforming_Chemical_Energy.txt |
Learning Objectives
• Compare the two methods by which cells utilize ATP for energy.
ATP in Living Systems
A living cell cannot store significant amounts of free energy. Excess free energy would result in an increase of heat in the cell, which would lead to excessive thermal motion that could damage and then destroy the cell. Rather, a cell must be able to handle that energy in a way that enables the cell to store energy safely and release it for use as needed. Living cells accomplish this by using the compound adenosine triphosphate (ATP). ATP is often called the “energy currency” of the cell and can be used to fill any energy need of the cell.
ATP Structure and Function
The core of ATP is a molecule of adenosine monophosphate (AMP), which is composed of an adenine molecule bonded to a ribose molecule and to a single phosphate group. Ribose is a five-carbon sugar found in RNA, and AMP is one of the nucleotides in RNA. The addition of a second phosphate group to this core molecule results in the formation of adenosine diphosphate (ADP); the addition of a third phosphate group forms adenosine triphosphate (ATP).
The addition of a phosphate group to a molecule requires energy. Phosphate groups are negatively charged and, thus, repel one another when they are arranged in a series, as they are in ADP and ATP. This repulsion makes the ADP and ATP molecules inherently unstable. The release of one or two phosphate groups from ATP, a process called dephosphorylation, releases energy.
Energy from ATP
Hydrolysis is the process of breaking complex macromolecules apart. During hydrolysis, water is split, or lysed, and the resulting hydrogen atom (H+) and a hydroxyl group (OH) are added to the larger molecule. The hydrolysis of ATP produces ADP, together with an inorganic phosphate ion (Pi), and the release of free energy. To carry out life processes, ATP is continuously broken down into ADP, and, like a rechargeable battery, ADP is continuously regenerated into ATP by the reattachment of a third phosphate group. Water, which was broken down into its hydrogen atom and hydroxyl group during ATP hydrolysis, is regenerated when a third phosphate is added to the ADP molecule, reforming ATP.
Obviously, energy must be infused into the system to regenerate ATP. In nearly every living thing on earth, the energy comes from the metabolism of glucose. In this way, ATP is a direct link between the limited set of exergonic pathways of glucose catabolism and the multitude of endergonic pathways that power living cells.
Phosphorylation
When ATP is broken down by the removal of its terminal phosphate group, energy is released and can be used to do work by the cell. Often the released phosphate is directly transferred to another molecule, such as a protein, activating it. For example, ATP supplies the energy to move the contractile muscle proteins during the mechanical work of muscle contraction. Recall the active transport work of the sodium-potassium pump in cell membranes. Phosphorylation by ATP alters the structure of the integral protein that functions as the pump, changing its affinity for sodium and potassium. In this way, the cell performs work, using energy from ATP to pump ions against their electrochemical gradients.
Sometimes phosphorylation of an enzyme leads to its inhibition. For example, the pyruvate dehydrogenase (PDH) complex could be phosphorylated by pyruvate dehydrogenase kinase (PDHK). This reaction leads to inhibition of PDH and its inability to convert pyruvate into acetyl-CoA.
Energy from ATP hydrolysis
The energy from ATP can also be used to drive chemical reactions by coupling ATP hydrolysis with another reaction process in an enzyme. In many cellular chemical reactions, enzymes bind to several substrates or reactants to form a temporary intermediate complex that allow the substrates and reactants to more readily react with each other. In reactions where ATP is involved, ATP is one of the substrates and ADP is a product. During an endergonic chemical reaction, ATP forms an intermediate complex with the substrate and enzyme in the reaction. This intermediate complex allows the ATP to transfer its third phosphate group, with its energy, to the substrate, a process called phosphorylation. Phosphorylation refers to the addition of the phosphate (~P). When the intermediate complex breaks apart, the energy is used to modify the substrate and convert it into a product of the reaction. The ADP molecule and a free phosphate ion are released into the medium and are available for recycling through cell metabolism. This is illustrated by the following generic reaction:
A + enzyme + ATP→[ A enzyme −P ] B + enzyme + ADP + phosphate ion
Key Points
• Cells require a constant supply of energy to survive, but cannot store this energy as free energy as this would result in elevated temperatures and would destroy the cell.
• Cells store energy in the form of adenosine triphosphate, or ATP.
• Energy is released when the terminal phosphate group is removed from ATP.
• To utilize the energy stored as ATP, cells either couple ATP hydrolysis to an energetically unfavorable reaction to allow it to proceed or transfer one of the phosphate groups from ATP to a protein substrate, causing it to change conformations and hence energetic preference.
Key Terms
• phosphorylation: the addition of a phosphate group to a compound; often catalyzed by enzymes
• adenosine triphosphate: a multifunctional nucleoside triphosphate used in cells as a coenzyme, often called the “molecular unit of energy currency” in intracellular energy transfer
• phosphate: Any salt or ester of phosphoric acid
Contributions and Attributions
• adenosine triphosphate. Provided by: Wikipedia. Located at: en.Wikipedia.org/wiki/adenosine%20triphosphate. License: CC BY-SA: Attribution-ShareAlike
• OpenStax College, Biology. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44430/latest...ol11448/latest. License: CC BY: Attribution
• cellular respiration. Provided by: Wikipedia. Located at: en.Wikipedia.org/wiki/cellular%20respiration. License: CC BY-SA: Attribution-ShareAlike
• photosynthesis. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/photosynthesis. License: CC BY-SA: Attribution-ShareAlike
• OpenStax College, Introduction. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44430/latest...e_07_00_01.jpg. License: CC BY: Attribution
• OpenStax College, Biology. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44431/latest...ol11448/latest. License: CC BY: Attribution
• reduction. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/reduction. License: CC BY-SA: Attribution-ShareAlike
• oxidation. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/oxidation. License: CC BY-SA: Attribution-ShareAlike
• Boundless. Provided by: Boundless Learning. Located at: www.boundless.com//biology/de...ectron-shuttle. License: CC BY-SA: Attribution-ShareAlike
• nicotinamide adenine dinucleotide. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/nicoti...e_dinucleotide. License: CC BY-SA: Attribution-ShareAlike
• OpenStax College, Introduction. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44430/latest...e_07_00_01.jpg. License: CC BY: Attribution
• OpenStax College, Energy in Living Systems. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44431/latest...07_01_01ab.jpg. License: CC BY: Attribution
• adenosine triphosphate. Provided by: Wikipedia. Located at: en.Wikipedia.org/wiki/adenosine%20triphosphate. License: CC BY-SA: Attribution-ShareAlike
• OpenStax College, Biology. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44431/latest...ol11448/latest. License: CC BY: Attribution
• phosphorylation. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/phosphorylation. License: CC BY-SA: Attribution-ShareAlike
• phosphate. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/phosphate. License: CC BY-SA: Attribution-ShareAlike
• OpenStax College, Introduction. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44430/latest...e_07_00_01.jpg. License: CC BY: Attribution
• OpenStax College, Energy in Living Systems. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44431/latest...07_01_01ab.jpg. License: CC BY: Attribution
• OpenStax College, Energy in Living Systems. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44431/latest...e_07_01_03.jpg. License: CC BY: Attribution
• OpenStax College, Energy in Living Systems. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44431/latest...e_07_01_02.jpg. License: CC BY: Attribution | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/07%3A_Cellular_Respiration/7.03%3A_Energy_in_Living_Systems_-_ATP_in_Metabolism.txt |
Learning Objectives
• Explain the importance of glycolysis to cells
Nearly all of the energy used by living cells comes to them from the energy in the bonds of the sugar glucose. Glucose enters heterotrophic cells in two ways. One method is through secondary active transport in which the transport takes place against the glucose concentration gradient. The other mechanism uses a group of integral proteins called GLUT proteins, also known as glucose transporter proteins. These transporters assist in the facilitated diffusion of glucose. Glycolysis is the first pathway used in the breakdown of glucose to extract energy. It takes place in the cytoplasm of both prokaryotic and eukaryotic cells. It was probably one of the earliest metabolic pathways to evolve since it is used by nearly all of the organisms on earth. The process does not use oxygen and is, therefore, anaerobic.
Glycolysis is the first of the main metabolic pathways of cellular respiration to produce energy in the form of ATP. Through two distinct phases, the six-carbon ring of glucose is cleaved into two three-carbon sugars of pyruvate through a series of enzymatic reactions. The first phase of glycolysis requires energy, while the second phase completes the conversion to pyruvate and produces ATP and NADH for the cell to use for energy. Overall, the process of glycolysis produces a net gain of two pyruvate molecules, two ATP molecules, and two NADH molecules for the cell to use for energy. Following the conversion of glucose to pyruvate, the glycolytic pathway is linked to the Krebs Cycle, where further ATP will be produced for the cell’s energy needs.
Key Points
• Glycolysis is present in nearly all living organisms.
• Glucose is the source of almost all energy used by cells.
• Overall, glycolysis produces two pyruvate molecules, a net gain of two ATP molecules, and two NADH molecules.
Key Terms
• glycolysis: the cellular metabolic pathway of the simple sugar glucose to yield pyruvic acid and ATP as an energy source
• heterotroph: an organism that requires an external supply of energy in the form of food, as it cannot synthesize its own
7.05: Glycolysis - The Energy-Requiring Steps of Glycolysis
Learning Objectives
• Outline the energy-requiring steps of glycolysis
First Half of Glycolysis (Energy-Requiring Steps)
In the first half of glycolysis, two adenosine triphosphate (ATP) molecules are used in the phosphorylation of glucose, which is then split into two three-carbon molecules as described in the following steps.
Step 1. The first step in glycolysis is catalyzed by hexokinase, an enzyme with broad specificity that catalyzes the phosphorylation of six-carbon sugars. Hexokinase phosphorylates glucose using ATP as the source of the phosphate, producing glucose-6-phosphate, a more reactive form of glucose. This reaction prevents the phosphorylated glucose molecule from continuing to interact with the GLUT proteins. It can no longer leave the cell because the negatively-charged phosphate will not allow it to cross the hydrophobic interior of the plasma membrane.
Step 2. In the second step of glycolysis, an isomerase converts glucose-6-phosphate into one of its isomers, fructose-6-phosphate. An enzyme that catalyzes the conversion of a molecule into one of its isomers is an isomerase. (This change from phosphoglucose to phosphofructose allows the eventual split of the sugar into two three-carbon molecules).
Step 3. The third step is the phosphorylation of fructose-6-phosphate, catalyzed by the enzyme phosphofructokinase. A second ATP molecule donates a high-energy phosphate to fructose-6-phosphate, producing fructose-1,6-bisphosphate. In this pathway, phosphofructokinase is a rate-limiting enzyme. It is active when the concentration of ADP is high; it is less active when ADP levels are low and the concentration of ATP is high. Thus, if there is “sufficient” ATP in the system, the pathway slows down. This is a type of end-product inhibition, since ATP is the end product of glucose catabolism.
Step 4. The newly-added high-energy phosphates further destabilize fructose-1,6-bisphosphate. The fourth step in glycolysis employs an enzyme, aldolase, to cleave 1,6-bisphosphate into two three-carbon isomers: dihydroxyacetone-phosphate and glyceraldehyde-3-phosphate.
Step 5. In the fifth step, an isomerase transforms the dihydroxyacetone-phosphate into its isomer, glyceraldehyde-3-phosphate. Thus, the pathway will continue with two molecules of a single isomer. At this point in the pathway, there is a net investment of energy from two ATP molecules in the breakdown of one glucose molecule.
Key Points
• ATP molecules donate high energy phosphate groups during the two phosphorylation steps, step 1 with hexokinase and step 3 with phosphofructokinase, in the first half of glycolysis.
• In steps 2 and 5, isomerases convert molecules into their isomers to allow glucose to be split eventually into two molecules of glyceraldehyde-3-phosphate, which continues into the second half of glycolysis.
• The enzyme aldolase in step 4 of glycolysis cleaves the six-carbon sugar 1,6-bisphosphate into two three-carbon sugar isomers, dihydroxyacetone-phosphate and glyceraldehyde-3-phosphate.
Key Terms
• glucose: a simple monosaccharide (sugar) with a molecular formula of C6H12O6; it is a principal source of energy for cellular metabolism
• adenosine triphosphate: a multifunctional nucleoside triphosphate used in cells as a coenzyme, often called the “molecular unit of energy currency” in intracellular energy transfer | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/07%3A_Cellular_Respiration/7.04%3A_Glycolysis_-_Importance_of_Glycolysis.txt |
Learning Objectives
• Outline the energy-releasing steps of glycolysis
Second Half of Glycolysis (Energy-Releasing Steps)
So far, glycolysis has cost the cell two ATP molecules and produced two small, three-carbon sugar molecules. Both of these molecules will proceed through the second half of the pathway where sufficient energy will be extracted to pay back the two ATP molecules used as an initial investment while also producing a profit for the cell of two additional ATP molecules and two even higher-energy NADH molecules.
Step 6. The sixth step in glycolysis oxidizes the sugar (glyceraldehyde-3-phosphate), extracting high-energy electrons, which are picked up by the electron carrier NAD+, producing NADH. The sugar is then phosphorylated by the addition of a second phosphate group, producing 1,3-bisphosphoglycerate. Note that the second phosphate group does not require another ATP molecule.
Here, again, there is a potential limiting factor for this pathway. The continuation of the reaction depends upon the availability of the oxidized form of the electron carrier NAD+. Thus, NADH must be continuously oxidized back into NAD+ in order to keep this step going. If NAD+ is not available, the second half of glycolysis slows down or stops. If oxygen is available in the system, the NADH will be oxidized readily, though indirectly, and the high-energy electrons from the hydrogen released in this process will be used to produce ATP. In an environment without oxygen, an alternate pathway (fermentation) can provide the oxidation of NADH to NAD+.
Step 7. In the seventh step, catalyzed by phosphoglycerate kinase (an enzyme named for the reverse reaction), 1,3-bisphosphoglycerate donates a high-energy phosphate to ADP, forming one molecule of ATP. (This is an example of substrate-level phosphorylation. ) A carbonyl group on the 1,3-bisphosphoglycerate is oxidized to a carboxyl group, and 3-phosphoglycerate is formed.
Step 8. In the eighth step, the remaining phosphate group in 3-phosphoglycerate moves from the third carbon to the second carbon, producing 2-phosphoglycerate (an isomer of 3-phosphoglycerate). The enzyme catalyzing this step is a mutase (isomerase).
Step 9. Enolase catalyzes the ninth step. This enzyme causes 2-phosphoglycerate to lose water from its structure; this is a dehydration reaction, resulting in the formation of a double bond that increases the potential energy in the remaining phosphate bond and produces phosphoenolpyruvate (PEP).
Step 10. The last step in glycolysis is catalyzed by the enzyme pyruvate kinase (the enzyme in this case is named for the reverse reaction of pyruvate’s conversion into PEP) and results in the production of a second ATP molecule by substrate-level phosphorylation and the compound pyruvic acid (or its salt form, pyruvate). Many enzymes in enzymatic pathways are named for the reverse reactions since the enzyme can catalyze both forward and reverse reactions (these may have been described initially by the reverse reaction that takes place in vitro, under non-physiological conditions).
Key Points
• The net energy release in glycolysis is a result of two molecules of glyceraldehyde-3- phosphate entering the second half of glycolysis where they are converted to pyruvic acid.
• Substrate -level phosphorylation, where a substrate of glycolysis donates a phosphate to ADP, occurs in two steps of the second-half of glycolysis to produce ATP.
• The availability of NAD+ is a limiting factor for the steps of glycolysis; when it is unavailable, the second half of glycolysis slows or shuts down.
Key Terms
• NADH: nicotinamide adenine dinucleotide (NAD) carrying two electrons and bonded with a hydrogen (H) ion; the reduced form of NAD
7.07: Glycolysis - Outcomes of Glycolysis
Learning Objectives
• Describe the energy obtained from one molecule of glucose going through glycolysis
Outcomes of Glycolysis
Glycolysis starts with one molecule of glucose and ends with two pyruvate (pyruvic acid) molecules, a total of four ATP molecules, and two molecules of NADH. Two ATP molecules were used in the first half of the pathway to prepare the six-carbon ring for cleavage, so the cell has a net gain of two ATP molecules and 2 NADH molecules for its use. If the cell cannot catabolize the pyruvate molecules further (via the citric acid cycle or Krebs cycle), it will harvest only two ATP molecules from one molecule of glucose.
Mature mammalian red blood cells do not have mitochondria and are not capable of aerobic respiration, the process in which organisms convert energy in the presence of oxygen. Instead, glycolysis is their sole source of ATP. Therefore, if glycolysis is interrupted, the red blood cells lose their ability to maintain their sodium-potassium pumps, which require ATP to function, and eventually, they die. For example, since the second half of glycolysis (which produces the energy molecules) slows or stops in the absence of NAD+, when NAD+ is unavailable, red blood cells will be unable to produce a sufficient amount of ATP in order to survive.
Additionally, the last step in glycolysis will not occur if pyruvate kinase, the enzyme that catalyzes the formation of pyruvate, is not available in sufficient quantities. In this situation, the entire glycolysis pathway will continue to proceed, but only two ATP molecules will be made in the second half (instead of the usual four ATP molecules). Thus, pyruvate kinase is a rate-limiting enzyme for glycolysis.
Key Points
• Although four ATP molecules are produced in the second half, the net gain of glycolysis is only two ATP because two ATP molecules are used in the first half of glycolysis.
• Enzymes that catalyze the reactions that produce ATP are rate-limiting steps of glycolysis and must be present in sufficient quantities for glycolysis to complete the production of four ATP, two NADH, and two pyruvate molecules for each glucose molecule that enters the pathway.
• Red blood cells require glycolysis as their sole source of ATP in order to survive, because they do not have mitochondria.
• Cancer cells and stem cells also use glycolysis as the main source of ATP (process known as aerobic glycolysis, or Warburg effect).
Key Terms
• pyruvate: any salt or ester of pyruvic acid; the end product of glycolysis before entering the TCA cycle | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/07%3A_Cellular_Respiration/7.06%3A_Glycolysis_-_The_Energy-Releasing_Steps_of_Glycolysis.txt |
Learning Objectives
• Explain why cells break down pyruvate
Breakdown of Pyruvate
In order for pyruvate, the product of glycolysis, to enter the next pathway, it must undergo several changes to become acetyl Coenzyme A (acetyl CoA). Acetyl CoA is a molecule that is further converted to oxaloacetate, which enters the citric acid cycle (Krebs cycle). The conversion of pyruvate to acetyl CoA is a three-step process.
Step 1. A carboxyl group is removed from pyruvate, releasing a molecule of carbon dioxide into the surrounding medium. (Note: carbon dioxide is one carbon attached to two oxygen atoms and is one of the major end products of cellular respiration. ) The result of this step is a two-carbon hydroxyethyl group bound to the enzyme pyruvate dehydrogenase; the lost carbon dioxide is the first of the six carbons from the original glucose molecule to be removed. This step proceeds twice for every molecule of glucose metabolized (remember: there are two pyruvate molecules produced at the end of glycolysis); thus, two of the six carbons will have been removed at the end of both of these steps.
Step 2. The hydroxyethyl group is oxidized to an acetyl group, and the electrons are picked up by NAD+, forming NADH (the reduced form of NAD+). The high- energy electrons from NADH will be used later by the cell to generate ATP for energy.
Step 3. The enzyme-bound acetyl group is transferred to CoA, producing a molecule of acetyl CoA. This molecule of acetyl CoA is then further converted to be used in the next pathway of metabolism, the citric acid cycle.
Key Points
• In the conversion of pyruvate to acetyl CoA, each pyruvate molecule loses one carbon atom with the release of carbon dioxide.
• During the breakdown of pyruvate, electrons are transferred to NAD+ to produce NADH, which will be used by the cell to produce ATP.
• In the final step of the breakdown of pyruvate, an acetyl group is transferred to Coenzyme A to produce acetyl CoA.
Key Terms
• acetyl CoA: a molecule that conveys the carbon atoms from glycolysis (pyruvate) to the citric acid cycle to be oxidized for energy production
7.09: Oxidation of Pyruvate and the Citric Acid Cycle - Acetyl CoA to CO
Learning Objectives
• Describe the fate of the acetyl CoA carbons in the citric acid cycle
Acetyl CoA to CO2
Acetyl CoA links glycolysis and pyruvate oxidation with the citric acid cycle. In the presence of oxygen, acetyl CoA delivers its acetyl group to a four-carbon molecule, oxaloacetate, to form citrate, a six-carbon molecule with three carboxyl groups. During this first step of the citric acid cycle, the CoA enzyme, which contains a sulfhydryl group (-SH), is recycled and becomes available to attach another acetyl group. The citrate will then harvest the remainder of the extractable energy from what began as a glucose molecule and continue through the citric acid cycle.
In the citric acid cycle, the two carbons that were originally the acetyl group of acetyl CoA are released as carbon dioxide, one of the major products of cellular respiration, through a series of enzymatic reactions. For each acetyl CoA that enters the citric acid cycle, two carbon dioxide molecules are released in reactions that are coupled with the production of NADH molecules from the reduction of NAD+ molecules.
In addition to the citric acid cycle, named for the first intermediate formed, citric acid, or citrate, when acetate joins to the oxaloacetate, the cycle is also known by two other names. The TCA cycle is named for tricarboxylic acids (TCA) because citric acid (or citrate) and isocitrate, the first two intermediates that are formed, are tricarboxylic acids. Additionally, the cycle is known as the Krebs cycle, named after Hans Krebs, who first identified the steps in the pathway in the 1930s in pigeon flight muscle.
Key Points
• The citric acid cycle is also known as the Krebs cycle or the TCA (tricarboxylic acid) cycle.
• Acetyl CoA transfers its acetyl group to oxaloacetate to form citrate and begin the citric acid cycle.
• The release of carbon dioxide is coupled with the reduction of NAD+ to NADH in the citric acid cycle.
Key Terms
• TCA cycle: an alternative name for the Krebs cycle or citric acid cycle
• Krebs cycle: a series of enzymatic reactions that occurs in all aerobic organisms; it involves the oxidative metabolism of acetyl units and serves as the main source of cellular energy
• oxaloacetate: a four carbon molecule that receives an acetyl group from acetyl CoA to form citrate, which enters the citric acid cycle | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/07%3A_Cellular_Respiration/7.08%3A_Oxidation_of_Pyruvate_and_the_Citric_Acid_Cycle_-__Breakdown_of_Pyruvate.txt |
Learning Objectives
• List the steps of the Krebs (or citric acid) cycle
Citric Acid Cycle (Krebs Cycle)
Like the conversion of pyruvate to acetyl CoA, the citric acid cycle takes place in the matrix of the mitochondria. Almost all of the enzymes of the citric acid cycle are soluble, with the single exception of the enzyme succinate dehydrogenase, which is embedded in the inner membrane of the mitochondrion. Unlike glycolysis, the citric acid cycle is a closed loop: the last part of the pathway regenerates the compound used in the first step. The eight steps of the cycle are a series of redox, dehydration, hydration, and decarboxylation reactions that produce two carbon dioxide molecules, one GTP/ATP, and reduced forms of NADH and FADH2. This is considered an aerobic pathway because the NADH and FADH2 produced must transfer their electrons to the next pathway in the system, which will use oxygen. If this transfer does not occur, the oxidation steps of the citric acid cycle also do not occur. Note that the citric acid cycle produces very little ATP directly and does not directly consume oxygen.
Steps in the Citric Acid Cycle
Step 1. The first step is a condensation step, combining the two-carbon acetyl group (from acetyl CoA) with a four-carbon oxaloacetate molecule to form a six-carbon molecule of citrate. CoA is bound to a sulfhydryl group (-SH) and diffuses away to eventually combine with another acetyl group. This step is irreversible because it is highly exergonic. The rate of this reaction is controlled by negative feedback and the amount of ATP available. If ATP levels increase, the rate of this reaction decreases. If ATP is in short supply, the rate increases.
Step 2. Citrate loses one water molecule and gains another as citrate is converted into its isomer, isocitrate.
Steps 3 and 4. In step three, isocitrate is oxidized, producing a five-carbon molecule, α-ketoglutarate, together with a molecule of CO2and two electrons, which reduce NAD+ to NADH. This step is also regulated by negative feedback from ATP and NADH and by a positive effect of ADP. Steps three and four are both oxidation and decarboxylation steps, which release electrons that reduce NAD+ to NADH and release carboxyl groups that form CO2 molecules. α-Ketoglutarate is the product of step three, and a succinyl group is the product of step four. CoA binds the succinyl group to form succinyl CoA. The enzyme that catalyzes step four is regulated by feedback inhibition of ATP, succinyl CoA, and NADH.
Step 5. A phosphate group is substituted for coenzyme A, and a high- energy bond is formed. This energy is used in substrate-level phosphorylation (during the conversion of the succinyl group to succinate) to form either guanine triphosphate (GTP) or ATP. There are two forms of the enzyme, called isoenzymes, for this step, depending upon the type of animal tissue in which they are found. One form is found in tissues that use large amounts of ATP, such as heart and skeletal muscle. This form produces ATP. The second form of the enzyme is found in tissues that have a high number of anabolic pathways, such as liver. This form produces GTP. GTP is energetically equivalent to ATP; however, its use is more restricted. In particular, protein synthesis primarily uses GTP.
Step 6. Step six is a dehydration process that converts succinate into fumarate. Two hydrogen atoms are transferred to FAD, producing FADH2. The energy contained in the electrons of these atoms is insufficient to reduce NAD+ but adequate to reduce FAD. Unlike NADH, this carrier remains attached to the enzyme and transfers the electrons to the electron transport chain directly. This process is made possible by the localization of the enzyme catalyzing this step inside the inner membrane of the mitochondrion.
Step 7. Water is added to fumarate during step seven, and malate is produced. The last step in the citric acid cycle regenerates oxaloacetate by oxidizing malate. Another molecule of NADH is produced.
Products of the Citric Acid Cycle
Two carbon atoms come into the citric acid cycle from each acetyl group, representing four out of the six carbons of one glucose molecule. Two carbon dioxide molecules are released on each turn of the cycle; however, these do not necessarily contain the most recently-added carbon atoms. The two acetyl carbon atoms will eventually be released on later turns of the cycle; thus, all six carbon atoms from the original glucose molecule are eventually incorporated into carbon dioxide. Each turn of the cycle forms three NADH molecules and one FADH2 molecule. These carriers will connect with the last portion of aerobic respiration to produce ATP molecules. One GTP or ATP is also made in each cycle. Several of the intermediate compounds in the citric acid cycle can be used in synthesizing non-essential amino acids; therefore, the cycle is amphibolic (both catabolic and anabolic).
Key Points
• The four-carbon molecule, oxaloacetate, that began the cycle is regenerated after the eight steps of the citric acid cycle.
• The eight steps of the citric acid cycle are a series of redox, dehydration, hydration, and decarboxylation reactions.
• Each turn of the cycle forms one GTP or ATP as well as three NADH molecules and one FADH2 molecule, which will be used in further steps of cellular respiration to produce ATP for the cell.
Key Terms
• citric acid cycle: a series of chemical reactions used by all aerobic organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats, and proteins into carbon dioxide
• Krebs cycle: a series of enzymatic reactions that occurs in all aerobic organisms; it involves the oxidative metabolism of acetyl units and serves as the main source of cellular energy
• mitochondria: in cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed organelle, often described as “cellular power plants” because they generate most of the ATP
Contributions and Attributions
• OpenStax College, Biology. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44433/latest...ol11448/latest. License: CC BY: Attribution
• acetyl CoA. Provided by: Wikipedia. Located at: en.Wikipedia.org/wiki/acetyl%20CoA. License: CC BY-SA: Attribution-ShareAlike
• 09 10PyruvateToAcetylCoA-L. Provided by: Wikimedia. Located at: commons.wikimedia.org/wiki/Fi...cetylCoA-L.jpg. License: CC BY: Attribution
• Krebs cycle. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/Krebs_cycle. License: CC BY-SA: Attribution-ShareAlike
• OpenStax College, Biology. October 29, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44433/latest...ol11448/latest. License: CC BY: Attribution
• Boundless. Provided by: Boundless Learning. Located at: www.boundless.com//biology/de...tion/tca-cycle. License: CC BY-SA: Attribution-ShareAlike
• Boundless. Provided by: Boundless Learning. Located at: www.boundless.com//biology/de...n/oxaloacetate. License: CC BY-SA: Attribution-ShareAlike
• 09 10PyruvateToAcetylCoA-L. Provided by: Wikimedia. Located at: commons.wikimedia.org/wiki/Fi...cetylCoA-L.jpg. License: CC BY: Attribution
• OpenStax College, Oxidation of Pyruvate and the Citric Acid Cycle. November 10, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44433/latest/. License: CC BY: Attribution
• Krebs cycle. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/Krebs_cycle. License: CC BY-SA: Attribution-ShareAlike
• OpenStax College, Biology. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44433/latest...ol11448/latest. License: CC BY: Attribution
• mitochondria. Provided by: Wikipedia. Located at: en.Wikipedia.org/wiki/mitochondria. License: CC BY-SA: Attribution-ShareAlike
• citric acid cycle. Provided by: Wikipedia. Located at: en.Wikipedia.org/wiki/citric%20acid%20cycle. License: CC BY-SA: Attribution-ShareAlike
• 09 10PyruvateToAcetylCoA-L. Provided by: Wikimedia. Located at: commons.wikimedia.org/wiki/Fi...cetylCoA-L.jpg. License: CC BY: Attribution
• OpenStax College, Oxidation of Pyruvate and the Citric Acid Cycle. November 10, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44433/latest/. License: CC BY: Attribution
• OpenStax College, Oxidation of Pyruvate and the Citric Acid Cycle. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44433/latest...e_07_03_02.jpg. License: CC BY: Attribution | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/07%3A_Cellular_Respiration/7.10%3A_Oxidation_of_Pyruvate_and_the_Citric_Acid_Cycle_-__Citric_Acid_Cycle.txt |
The electron transport chain uses the electrons from electron carriers to create a chemical gradient that can be used to power oxidative phosphorylation.
Learning Objectives
• Describe how electrons move through the electron transport chain
Key Points
• Oxidative phosphorylation is the metabolic pathway in which electrons are transferred from electron donors to electron acceptors in redox reactions; this series of reactions releases energy which is used to form ATP.
• There are four protein complexes (labeled complex I-IV) in the electron transport chain, which are involved in moving electrons from NADH and FADH2 to molecular oxygen.
• Complex I establishes the hydrogen ion gradient by pumping four hydrogen ions across the membrane from the matrix into the intermembrane space.
• Complex II receives FADH2, which bypasses complex I, and delivers electrons directly to the electron transport chain.
• Ubiquinone (Q) accepts the electrons from both complex I and complex II and delivers them to complex III.
• Complex III pumps protons through the membrane and passes its electrons to cytochrome c for transport to the fourth complex of proteins and enzymes.
• Complex IV reduces oxygen; the reduced oxygen then picks up two hydrogen ions from the surrounding medium to make water.
Key Terms
• prosthetic group: The non-protein component of a conjugated protein.
• complex: A structure consisting of a central atom, molecule, or protein weakly connected to surrounding atoms, molecules, or proteins.
• ubiquinone: A lipid soluble substance that is a component of the electron transport chain and accepts electrons from complexes I and II.
Oxidative phosphorylation is a highly efficient method of producing large amounts of ATP, the basic unit of energy for metabolic processes. During this process electrons are exchanged between molecules, which creates a chemical gradient that allows for the production of ATP. The most vital part of this process is the electron transport chain, which produces more ATP than any other part of cellular respiration.
Electron Transport Chain
The electron transport chain is the final component of aerobic respiration and is the only part of glucose metabolism that uses atmospheric oxygen. Electron transport is a series of redox reactions that resemble a relay race. Electrons are passed rapidly from one component to the next to the endpoint of the chain, where the electrons reduce molecular oxygen, producing water. This requirement for oxygen in the final stages of the chain can be seen in the overall equation for cellular respiration, which requires both glucose and oxygen.
A complex is a structure consisting of a central atom, molecule, or protein weakly connected to surrounding atoms, molecules, or proteins. The electron transport chain is an aggregation of four of these complexes (labeled I through IV), together with associated mobile electron carriers. The electron transport chain is present in multiple copies in the inner mitochondrial membrane of eukaryotes and the plasma membrane of prokaryotes.
Complex I
To start, two electrons are carried to the first complex aboard NADH. Complex I is composed of flavin mononucleotide (FMN) and an enzyme containing iron-sulfur (Fe-S). FMN, which is derived from vitamin B2 (also called riboflavin), is one of several prosthetic groups or co-factors in the electron transport chain. A prosthetic group is a non-protein molecule required for the activity of a protein. Prosthetic groups can be organic or inorganic and are non-peptide molecules bound to a protein that facilitate its function.
Prosthetic groups include co-enzymes, which are the prosthetic groups of enzymes. The enzyme in complex I is NADH dehydrogenase, a very large protein containing 45 amino acid chains. Complex I can pump four hydrogen ions across the membrane from the matrix into the intermembrane space; it is in this way that the hydrogen ion gradient is established and maintained between the two compartments separated by the inner mitochondrial membrane.
Q and Complex II
Complex II directly receives FADH2, which does not pass through complex I. The compound connecting the first and second complexes to the third is ubiquinone (Q). The Q molecule is lipid soluble and freely moves through the hydrophobic core of the membrane. Once it is reduced to QH2, ubiquinone delivers its electrons to the next complex in the electron transport chain. Q receives the electrons derived from NADH from complex I and the electrons derived from FADH2 from complex II, including succinate dehydrogenase. This enzyme and FADH2 form a small complex that delivers electrons directly to the electron transport chain, bypassing the first complex. Since these electrons bypass, and thus do not energize, the proton pump in the first complex, fewer ATP molecules are made from the FADH2 electrons. The number of ATP molecules ultimately obtained is directly proportional to the number of protons pumped across the inner mitochondrial membrane.
Complex III
The third complex is composed of cytochrome b, another Fe-S protein, Rieske center (2Fe-2S center), and cytochrome c proteins; this complex is also called cytochrome oxidoreductase. Cytochrome proteins have a prosthetic heme group. The heme molecule is similar to the heme in hemoglobin, but it carries electrons, not oxygen. As a result, the iron ion at its core is reduced and oxidized as it passes the electrons, fluctuating between different oxidation states: Fe2+ (reduced) and Fe3+ (oxidized). The heme molecules in the cytochromes have slightly different characteristics due to the effects of the different proteins binding them, which makes each complex. Complex III pumps protons through the membrane and passes its electrons to cytochrome c for transport to the fourth complex of proteins and enzymes. Cytochrome c is the acceptor of electrons from Q; however, whereas Q carries pairs of electrons, cytochrome c can accept only one at a time.
Complex IV
The fourth complex is composed of cytochrome proteins c, a, and a3. This complex contains two heme groups (one in each of the cytochromes a and a3) and three copper ions (a pair of CuA and one CuB in cytochrome a3). The cytochromes hold an oxygen molecule very tightly between the iron and copper ions until the oxygen is completely reduced. The reduced oxygen then picks up two hydrogen ions from the surrounding medium to produce water (H2O). The removal of the hydrogen ions from the system also contributes to the ion gradient used in the process of chemiosmosis. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/07%3A_Cellular_Respiration/7.11%3A_Oxidative_Phosphorylation_-_Electron_Transport_Chain.txt |
Learning Objectives
• Describe how the energy obtained from the electron transport chain powers chemiosmosis and discuss the role of hydrogen ions in the synthesis of ATP
During chemiosmosis, electron carriers like NADH and FADH donate electrons to the electron transport chain. The electrons cause conformation changes in the shapes of the proteins to pump H+ across a selectively permeable cell membrane. The uneven distribution of H+ ions across the membrane establishes both concentration and electrical gradients (thus, an electrochemical gradient) owing to the hydrogen ions’ positive charge and their aggregation on one side of the membrane.
If the membrane were open to diffusion by the hydrogen ions, the ions would tend to spontaneously diffuse back across into the matrix, driven by their electrochemical gradient. However, many ions cannot diffuse through the nonpolar regions of phospholipid membranes without the aid of ion channels. Similarly, hydrogen ions in the matrix space can only pass through the inner mitochondrial membrane through a membrane protein called ATP synthase. This protein acts as a tiny generator turned by the force of the hydrogen ions diffusing through it, down their electrochemical gradient. The turning of this molecular machine harnesses the potential energy stored in the hydrogen ion gradient to add a phosphate to ADP, forming ATP.
Chemiosmosis is used to generate 90 percent of the ATP made during aerobic glucose catabolism. The production of ATP using the process of chemiosmosis in mitochondria is called oxidative phosphorylation. It is also the method used in the light reactions of photosynthesis to harness the energy of sunlight in the process of photophosphorylation. The overall result of these reactions is the production of ATP from the energy of the electrons removed from hydrogen atoms. These atoms were originally part of a glucose molecule. At the end of the pathway, the electrons are used to reduce an oxygen molecule to oxygen ions. The extra electrons on the oxygen attract hydrogen ions (protons) from the surrounding medium and water is formed.
Key Points
• During chemiosmosis, the free energy from the series of reactions that make up the electron transport chain is used to pump hydrogen ions across the membrane, establishing an electrochemical gradient.
• Hydrogen ions in the matrix space can only pass through the inner mitochondrial membrane through a membrane protein called ATP synthase.
• As protons move through ATP synthase, ADP is turned into ATP.
• The production of ATP using the process of chemiosmosis in mitochondria is called oxidative phosphorylation.
Key Terms
• ATP synthase: An important enzyme that provides energy for the cell to use through the synthesis of adenosine triphosphate (ATP).
• oxidative phosphorylation: A metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate (ATP).
• chemiosmosis: The movement of ions across a selectively permeable membrane, down their electrochemical gradient.
7.13: Oxidative Phosphorylation - ATP Yield
ese atoms were originally part of a glucose molecule. At the end of the pathway, the electrons are used to reduce an oxygen molecule to oxygen ions. The extra electrons on the oxygen attract hydrogen ions (protons) from the surrounding medium and water is formed.
ATP Yield
The amount of energy (as ATP) gained from glucose catabolism varies across species and depends on other related cellular processes.
LEARNING OBJECTIVES
Describe the origins of variability in the amount of ATP that is produced per molecule of glucose consumed
Key Points
• While glucose catabolism always produces energy, the amount of energy (in terms of ATP equivalents) produced can vary, especially across different species.
• The number of hydrogen ions the electron transport chain complexes can pump through the membrane varies between species.
• NAD+ provides more ATP than FAD+ in the electron transport chain and can lead to variance in ATP production.
• The use of intermediates from glucose catabolism in other biosynthetic pathways, such as amino acid synthesis, can lower the yield of ATP.
Key Terms
• catabolism: Destructive metabolism, usually including the release of energy and breakdown of materials.
ATP Yield
In a eukaryotic cell, the process of cellular respiration can metabolize one molecule of glucose into 30 to 32 ATP. The process of glycolysis only produces two ATP, while all the rest are produced during the electron transport chain. Clearly, the electron transport chain is vastly more efficient, but it can only be carried out in the presence of oxygen.
The number of ATP molecules generated via the catabolism of glucose can vary substantially. For example, the number of hydrogen ions the electron transport chain complexes can pump through the membrane varies between species. Another source of variance occurs during the shuttle of electrons across the membranes of the mitochondria. The NADH generated from glycolysis cannot easily enter mitochondria. Thus, electrons are picked up on the inside of mitochondria by either NAD+ or FAD+. These FAD+ molecules can transport fewer ions; consequently, fewer ATP molecules are generated when FAD+ acts as a carrier. NAD+ is used as the electron transporter in the liver, and FAD+ acts in the brain.
Another factor that affects the yield of ATP molecules generated from glucose is the fact that intermediate compounds in these pathways are used for other purposes. Glucose catabolism connects with the pathways that build or break down all other biochemical compounds in cells, but the result is not always ideal. For example, sugars other than glucose are fed into the glycolytic pathway for energy extraction. Moreover, the five-carbon sugars that form nucleic acids are made from intermediates in glycolysis. Certain nonessential amino acids can be made from intermediates of both glycolysis and the citric acid cycle. Lipids, such as cholesterol and triglycerides, are also made from intermediates in these pathways, and both amino acids and triglycerides are broken down for energy through these pathways. Overall, in living systems, these pathways of glucose catabolism extract about 34 percent of the energy contained in glucose. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/07%3A_Cellular_Respiration/7.12%3A_Oxidative_Phosphorylation_-_Chemiosmosis_and_Oxidative_Phosphorylation.txt |
Some prokaryotes and eukaryotes use anaerobic respiration in which they can create energy for use in the absence of oxygen.
Learning Objectives
• Describe the process of anaerobic cellular respiration.
Key Points
• Anaerobic respiration is a type of respiration where oxygen is not used; instead, organic or inorganic molecules are used as final electron acceptors.
• Fermentation includes processes that use an organic molecule to regenerate NAD+ from NADH.
• Types of fermentation include lactic acid fermentation and alcohol fermentation, in which ethanol is produced.
• All forms of fermentation except lactic acid fermentation produce gas, which plays a role in the laboratory identification of bacteria.
• Some types of prokaryotes are facultatively anaerobic, which means that they can switch between aerobic respiration and fermentation, depending on the availability of oxygen.
Key Terms
• archaea: A group of single-celled microorganisms. They have no cell nucleus or any other membrane-bound organelles within their cells.
• anaerobic respiration: A form of respiration using electron acceptors other than oxygen.
• fermentation: An anaerobic biochemical reaction. When this reaction occurs in yeast, enzymes catalyze the conversion of sugars to alcohol or acetic acid with the evolution of carbon dioxide.
Anaerobic Cellular Respiration
The production of energy requires oxygen. The electron transport chain, where the majority of ATP is formed, requires a large input of oxygen. However, many organisms have developed strategies to carry out metabolism without oxygen, or can switch from aerobic to anaerobic cell respiration when oxygen is scarce.
During cellular respiration, some living systems use an organic molecule as the final electron acceptor. Processes that use an organic molecule to regenerate NAD+ from NADH are collectively referred to as fermentation. In contrast, some living systems use an inorganic molecule as a final electron acceptor. Both methods are called anaerobic cellular respiration, where organisms convert energy for their use in the absence of oxygen.
Certain prokaryotes, including some species of bacteria and archaea, use anaerobic respiration. For example, the group of archaea called methanogens reduces carbon dioxide to methane to oxidize NADH. These microorganisms are found in soil and in the digestive tracts of ruminants, such as cows and sheep. Similarly, sulfate-reducing bacteria and archaea, most of which are anaerobic, reduce sulfate to hydrogen sulfide to regenerate NAD+ from NADH.
Eukaryotes can also undergo anaerobic respiration. Some examples include alcohol fermentation in yeast and lactic acid fermentation in mammals.
Lactic Acid Fermentation
The fermentation method used by animals and certain bacteria (like those in yogurt) is called lactic acid fermentation. This type of fermentation is used routinely in mammalian red blood cells and in skeletal muscle that has an insufficient oxygen supply to allow aerobic respiration to continue (that is, in muscles used to the point of fatigue). The excess amount of lactate in those muscles is what causes the burning sensation in your legs while running. This pain is a signal to rest the overworked muscles so they can recover. In these muscles, lactic acid accumulation must be removed by the blood circulation and the lactate brought to the liver for further metabolism. The chemical reactions of lactic acid fermentation are the following:
Pyruvic acid + NADH ↔ lactic acid + NAD+
The enzyme used in this reaction is lactate dehydrogenase (LDH). The reaction can proceed in either direction, but the reaction from left to right is inhibited by acidic conditions. Such lactic acid accumulation was once believed to cause muscle stiffness, fatigue, and soreness, although more recent research disputes this hypothesis. Once the lactic acid has been removed from the muscle and circulated to the liver, it can be reconverted into pyruvic acid and further catabolized for energy.
Alcohol Fermentation
Another familiar fermentation process is alcohol fermentation, which produces ethanol, an alcohol. The use of alcohol fermentation can be traced back in history for thousands of years. The chemical reactions of alcoholic fermentation are the following (Note: CO2 does not participate in the second reaction):
Pyruvic acid → CO2 + acetaldehyde + NADH → ethanol + NAD+
The first reaction is catalyzed by pyruvate decarboxylase, a cytoplasmic enzyme, with a coenzyme of thiamine pyrophosphate (TPP, derived from vitamin B1 and also called thiamine). A carboxyl group is removed from pyruvic acid, releasing carbon dioxide as a gas. The loss of carbon dioxide reduces the size of the molecule by one carbon, making acetaldehyde. The second reaction is catalyzed by alcohol dehydrogenase to oxidize NADH to NAD+ and reduce acetaldehyde to ethanol.
The fermentation of pyruvic acid by yeast produces the ethanol found in alcoholic beverages. Ethanol tolerance of yeast is variable, ranging from about 5 percent to 21 percent, depending on the yeast strain and environmental conditions.
Other Types of Fermentation
Various methods of fermentation are used by assorted organisms to ensure an adequate supply of NAD+ for the sixth step in glycolysis. Without these pathways, that step would not occur and no ATP would be harvested from the breakdown of glucose.Other fermentation methods also occur in bacteria. Many prokaryotes are facultatively anaerobic. This means that they can switch between aerobic respiration and fermentation, depending on the availability of oxygen. Certain prokaryotes, like Clostridia, are obligate anaerobes. Obligate anaerobes live and grow in the absence of molecular oxygen. Oxygen is a poison to these microorganisms, killing them on exposure.
It should be noted that all forms of fermentation, except lactic acid fermentation, produce gas. The production of particular types of gas is used as an indicator of the fermentation of specific carbohydrates, which plays a role in the laboratory identification of the bacteria. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/07%3A_Cellular_Respiration/7.14%3A_Metabolism_without_Oxygen_-_Anaerobic_Cellular_Respiration.txt |
Sugars, such as galactose, fructose, and glycogen, are catabolized into new products in order to enter the glycolytic pathway.
Learning Objectives
• Identify the types of sugars involved in glucose metabolism
Key Points
• When blood sugar levels drop, glycogen is broken down into glucose -1-phosphate, which is then converted to glucose-6-phosphate and enters glycolysis for ATP production.
• In the liver, galactose is converted to glucose-6-phosphate in order to enter the glycolytic pathway.
• Fructose is converted into glycogen in the liver and then follows the same pathway as glycogen to enter glycolysis.
• Sucrose is broken down into glucose and fructose; glucose enters the pathway directly while fructose is converted to glycogen.
Key Terms
• disaccharide: A sugar, such as sucrose, maltose, or lactose, consisting of two monosaccharides combined together.
• glycogen: A polysaccharide that is the main form of carbohydrate storage in animals; converted to glucose as needed.
• monosaccharide: A simple sugar such as glucose, fructose, or deoxyribose that has a single ring.
You have learned about the catabolism of glucose, which provides energy to living cells. But living things consume more than glucose for food. How does a turkey sandwich end up as ATP in your cells? This happens because all of the catabolic pathways for carbohydrates, proteins, and lipids eventually connect into glycolysis and the citric acid cycle pathways.
Metabolic pathways should be thought of as porous; that is, substances enter from other pathways, and intermediates leave for other pathways. These pathways are not closed systems. Many of the substrates, intermediates, and products in a particular pathway are reactants in other pathways. Like sugars and amino acids, the catabolic pathways of lipids are also connected to the glucose catabolism pathways.
Glycogen, a polymer of glucose, is an energy-storage molecule in animals. When there is adequate ATP present, excess glucose is shunted into glycogen for storage. Glycogen is made and stored in both the liver and muscles. The glycogen is hydrolyzed into the glucose monomer, glucose-1-phosphate (G-1-P), if blood sugar levels drop. The presence of glycogen as a source of glucose allows ATP to be produced for a longer period of time during exercise. Glycogen is broken down into G-1-P and converted into glucose-6-phosphate (G-6-P) in both muscle and liver cells; this product enters the glycolytic pathway.
Galactose is the sugar in milk. Infants have an enzyme in the small intestine that metabolizes lactose to galactose and glucose. In areas where milk products are regularly consumed, adults have also evolved this enzyme. Galactose is converted in the liver to G-6-P and can thus enter the glycolytic pathway.
Fructose is one of the three dietary monosaccharides (along with glucose and galactose) which are absorbed directly into the bloodstream during digestion. Fructose is absorbed from the small intestine and then passes to the liver to be metabolized, primarily to glycogen. The catabolism of both fructose and galactose produces the same number of ATP molecules as glucose.
Sucrose is a disaccharide with a molecule of glucose and a molecule of fructose bonded together with a glycosidic linkage. The catabolism of sucrose breaks it down to monomers of glucose and fructose. The glucose can directly enter the glycolytic pathway while fructose must first be converted to glycogen, which can be broken down to G-1-P and enter the glycolytic pathway as described above.
7.16: Connections of Carbohydrate Protein and Lipid Metabolic Pathways - Connecting Proteins to Glucose Metabolism
Excess amino acids are converted into molecules that can enter the pathways of glucose catabolism.
Learning Objectives
• Describe the role played by proteins in glucose metabolism
Key Points
• Amino acids must be deaminated before entering any of the pathways of glucose catabolism: the amino group is converted to ammonia, which is used by the liver in the synthesis of urea.
• Deaminated amino acids can be converted into pyruvate, acetyl CoA, or some components of the citric acid cycle to enter the pathways of glucose catabolism.
• Several amino acids can enter the glucose catabolism pathways at multiple locations.
Key Terms
• catabolism: Destructive metabolism, usually including the release of energy and breakdown of materials.
• keto acid: Any carboxylic acid that also contains a ketone group.
• deamination: The removal of an amino group from a compound.
Metabolic pathways should be thought of as porous; that is, substances enter from other pathways and intermediates leave for other pathways. These pathways are not closed systems. Many of the substrates, intermediates, and products in a particular pathway are reactants in other pathways. Proteins are a good example of this phenomenon. They can be broken down into their constituent amino acids and used at various steps of the pathway of glucose catabolism.
Proteins are hydrolyzed by a variety of enzymes in cells. Most of the time, the amino acids are recycled into the synthesis of new proteins or are used as precursors in the synthesis of other important biological molecules, such as hormones, nucleotides, or neurotransmitters. However, if there are excess amino acids, or if the body is in a state of starvation, some amino acids will be shunted into the pathways of glucose catabolism.
Each amino acid must have its amino group removed (deamination) prior to the carbon chain’s entry into these pathways. When the amino group is removed from an amino acid, it is converted into ammonia through the urea cycle. The remaining atoms of the amino acid result in a keto acid: a carbon chain with one ketone and one carboxylic acid group. In mammals, the liver synthesizes urea from two ammonia molecules and a carbon dioxide molecule. Thus, urea is the principal waste product in mammals produced from the nitrogen originating in amino acids; it leaves the body in urine. The keto acid can then enter the citric acid cycle.
When deaminated, amino acids can enter the pathways of glucose metabolism as pyruvate, acetyl CoA, or several components of the citric acid cycle. For example, deaminated asparagine and aspartate are converted into oxaloacetate and enter glucose catabolism in the citric acid cycle. Deaminated amino acids can also be converted into another intermediate molecule before entering the pathways. Several amino acids can enter glucose catabolism at multiple locations. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/07%3A_Cellular_Respiration/7.15%3A_Connections_of_Carbohydrate_Protein_and_Lipid_Metabolic_Pathways_-_Connecting_Other_Sugars_to_Glucose_Metabolism.txt |
Lipids can be both made and broken down through parts of the glucose catabolism pathways.
Learning Objectives
• Explain the connection of lipids to glucose metabolism
Key Points
• Many types of lipids exist, but cholesterol and triglycerides are the lipids that enter the pathways of glucose catabolism.
• Through the process of phosphorylation, glycerol can be converted to glycerol-3-phosphate during the glycolytic pathway.
• When fatty acids are broken down into acetyl groups through beta-oxidation, the acetyl groups are used by CoA to form acetyl-CoA, which enters the citric acid cycle to produce ATP.
• Beta-oxidation produces FADH2 and NADH, which are used by the electron transport chain for ATP production.
Key Terms
• beta-oxidation: A process that takes place in the matrix of the mitochondria and catabolizes fatty acids by converting them to acetyl groups while producing NADH and FADH2.
• lipid: A group of organic compounds including fats, oils, waxes, sterols, and triglycerides; characterized by being insoluble in water; account for most of the fat present in the human body.
Like sugars and amino acids, the catabolic pathways of lipids are also connected to the glucose catabolism pathways. The lipids that are connected to the glucose pathways are cholesterol and triglycerides.
Cholesterol
Cholesterol contributes to cell membrane flexibility and is a precursor to steroid hormones. The synthesis of cholesterol starts with acetyl groups, which are transferred from acetyl CoA, and proceeds in only one direction; the process cannot be reversed. Thus, synthesis of cholesterol requires an intermediate of glucose metabolism.
Triglycerides
Triglycerides, a form of long-term energy storage in animals, are made of glycerol and three fatty acids. Animals can make most of the fatty acids they need. Triglycerides can be both made and broken down through parts of the glucose catabolism pathways. Glycerol can be phosphorylated to glycerol-3-phosphate, which continues through glycolysis.
Fatty acids are catabolized in a process called beta-oxidation that takes place in the matrix of the mitochondria and converts their fatty acid chains into two carbon units of acetyl groups, while producing NADH and FADH2. The acetyl groups are picked up by CoA to form acetyl CoA that proceeds into the citric acid cycle as it combines with oxaloacetate. The NADH and FADH2 are then used by the electron transport chain.
7.18: Regulation of Cellular Respiration - Regulatory Mechanisms for Cellular Respiration
Learning Objectives
• Explain the mechanisms that regulate cellular respiration.
Regulatory Mechanisms
Various mechanisms are used to control cellular respiration. As such, some type of control exists at each stage of glucose metabolism. Access of glucose to the cell can be regulated using the GLUT proteins that transport glucose. In addition, different forms of the GLUT protein control passage of glucose into the cells of specific tissues.
Some reactions are controlled by having two different enzymes: one each for the two directions of a reversible reaction. Reactions that are catalyzed by only one enzyme can go to equilibrium, stalling the reaction. In contrast, if two different enzymes (each specific for a given direction) are necessary for a reversible reaction, the opportunity to control the rate of the reaction increases and equilibrium is not reached.
A number of enzymes involved in each of the pathways (in particular, the enzyme catalyzing the first committed reaction of the pathway) are controlled by attachment of a molecule to an allosteric (non-active) site on the protein. This site has an effect on the enzyme’s activity, often by changing the conformation of the protein. The molecules most commonly used in this capacity are the nucleotides ATP, ADP, AMP, NAD+, and NADH. These regulators, known as allosteric effectors, may increase or decrease enzyme activity, depending on the prevailing conditions, altering the steric structure of the enzyme, usually affecting the configuration of the active site. This alteration of the protein’s (the enzyme’s) structure either increases or decreases its affinity for its substrate, with the effect of increasing or decreasing the rate of the reaction. The attachment of a molecule to the allosteric site serves to send a signal to the enzyme, providing feedback. This feedback type of control is effective as long as the chemical affecting it is bound to the enzyme. Once the overall concentration of the chemical decreases, it will diffuse away from the protein, and the control is relaxed.
Key Points
• Varying forms of the GLUT protein control the passage of glucose into the cells of specific tissues, thereby regulating cellular respiration.
• Reactions that are catalyzed by only one enzyme can go to equilibrium, which can cause the reaction to stall.
• If two different enzymes are necessary for a reversible reaction, there is greater opportunity to control the rate of the reaction and, as a result, equilibrium is reached less often.
• Enzymes are often controlled by binding of a molecule to an allosteric site on the protein.
Key Terms
• enzyme: a globular protein that catalyses a biological chemical reaction
• allosteric: a compound that binds to an inactive site, affecting the activity of an enzyme by changing the conformation of the protein (can activate or deactivate)
• metabolism: the complete set of chemical reactions that occur in living cells | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/07%3A_Cellular_Respiration/7.17%3A_Connections_of_Carbohydrate_Protein_and_Lipid_Metabolic_Pathways_-_Connecting_Lipids_to_Glucose_Metabolism.txt |
Learning Objectives
• Explain how catabolic pathways are controlled
Control of Catabolic Pathways
Enzymes, proteins, electron carriers, and pumps that play roles in glycolysis, the citric acid cycle, and the electron transport chain tend to catalyze non-reversible reactions. In other words, if the initial reaction takes place, the pathway is committed to proceeding with the remaining reactions. Whether a particular enzyme activity is released depends upon the energy needs of the cell (as reflected by the levels of ATP, ADP, and AMP).
Glycolysis
The control of glycolysis begins with the first enzyme in the pathway, hexokinase. This enzyme catalyzes the phosphorylation of glucose, which helps to prepare the compound for cleavage in a later step. The presence of the negatively-charged phosphate in the molecule also prevents the sugar from leaving the cell. When hexokinase is inhibited, glucose diffuses out of the cell and does not become a substrate for the respiration pathways in that tissue. The product of the hexokinase reaction is glucose-6-phosphate, which accumulates when a later enzyme, phosphofructokinase, is inhibited.
Phosphofructokinase is the main enzyme controlled in glycolysis. High levels of ATP, citrate, or a lower, more acidic pH decrease the enzyme’s activity. An increase in citrate concentration can occur because of a blockage in the citric acid cycle. Fermentation, with its production of organic acids like lactic acid, frequently accounts for the increased acidity in a cell; however, the products of fermentation do not typically accumulate in cells.
The last step in glycolysis is catalyzed by pyruvate kinase. The pyruvate produced can proceed to be catabolized or converted into the amino acid alanine. If no more energy is needed and alanine is in adequate supply, the enzyme is inhibited. The enzyme’s activity is increased when fructose-1,6-bisphosphate levels increase. (Recall that fructose-1,6-bisphosphate is an intermediate in the first half of glycolysis. ) The regulation of pyruvate kinase involves phosphorylation, resulting in a less-active enzyme. Dephosphorylation by a phosphatase reactivates it. Pyruvate kinase is also regulated by ATP (a negative allosteric effect).
If more energy is needed, more pyruvate will be converted into acetyl CoA through the action of pyruvate dehydrogenase. If either acetyl groups or NADH accumulate, there is less need for the reaction and the rate decreases. Pyruvate dehydrogenase is also regulated by phosphorylation: a kinase phosphorylates it to form an inactive enzyme, and a phosphatase reactivates it. The kinase and the phosphatase are also regulated.
Citric Acid Cycle
The citric acid cycle is controlled through the enzymes that catalyze the reactions that make the first two molecules of NADH. These enzymes are isocitrate dehydrogenase and α-ketoglutarate dehydrogenase. When adequate ATP and NADH levels are available, the rates of these reactions decrease. When more ATP is needed, as reflected in rising ADP levels, the rate increases. α-Ketoglutarate dehydrogenase will also be affected by the levels of succinyl CoA, a subsequent intermediate in the cycle, causing a decrease in activity. A decrease in the rate of operation of the pathway at this point is not necessarily negative as the increased levels of the α-ketoglutarate not used by the citric acid cycle can be used by the cell for amino acid (glutamate) synthesis.
Electron Transport Chain
Specific enzymes of the electron transport chain are unaffected by feedback inhibition, but the rate of electron transport through the pathway is affected by the levels of ADP and ATP. Greater ATP consumption by a cell is indicated by a buildup of ADP. As ATP usage decreases, the concentration of ADP decreases: ATP begins to build up in the cell. This change in the relative concentration of ADP to ATP triggers the cell to slow down the electron transport chain.
Key Points
• Glycolysis, the citric acid cycle, and the electron transport chain are catabolic pathways that bring forth non-reversible reactions.
• Glycolysis control begins with hexokinase, which catalyzes the phosphorylation of glucose; its product is glucose-6- phosphate, which accumulates when phosphofructokinase is inhibited.
• The citric acid cycle is controlled through the enzymes that break down the reactions that make the first two molecules of NADH.
• The rate of electron transport through the electron transport chain is affected by the levels of ADP and ATP, whereas specific enzymes of the electron transport chain are unaffected by feedback inhibition.
Key Terms
• phosphofructokinase: any of a group of kinase enzymes that convert fructose phosphates to biphosphate
• glycolysis: the cellular metabolic pathway of the simple sugar glucose to yield pyruvic acid and ATP as an energy source
• kinase: any of a group of enzymes that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific target molecules (substrates); the process is termed phosphorylation | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/07%3A_Cellular_Respiration/7.19%3A_Regulation_of_Cellular_Respiration_-_Control_of_Catabolic_Pathways.txt |
Learning Objectives
• Describe the process of photosynthesis
The Importance of Photosynthesis
The processes of all organisms—from bacteria to humans—require energy. To get this energy, many organisms access stored energy by eating food. Carnivores eat other animals and herbivores eat plants. But where does the stored energy in food originate? All of this energy can be traced back to the process of photosynthesis and light energy from the sun.
Photosynthesis is essential to all life on earth. It is the only biological process that captures energy from outer space (sunlight) and converts it into chemical energy in the form of G3P (
Glyceraldehyde 3-phosphate) which in turn can be made into sugars and other molecular compounds. Plants use these compounds in all of their metabolic processes; plants do not need to consume other organisms for food because they build all the molecules they need. Unlike plants, animals need to consume other organisms to consume the molecules they need for their metabolic processes.
The Process of Photosynthesis
During photosynthesis, molecules in leaves capture sunlight and energize electrons, which are then stored in the covalent bonds of carbohydrate molecules. That energy within those covalent bonds will be released when they are broken during cell respiration. How long lasting and stable are those covalent bonds? The energy extracted today by the burning of coal and petroleum products represents sunlight energy captured and stored by photosynthesis almost 200 million years ago.
Plants, algae, and a group of bacteria called cyanobacteria are the only organisms capable of performing photosynthesis. Because they use light to manufacture their own food, they are called photoautotrophs (“self-feeders using light”). Other organisms, such as animals, fungi, and most other bacteria, are termed heterotrophs (“other feeders”) because they must rely on the sugars produced by photosynthetic organisms for their energy needs. A third very interesting group of bacteria synthesize sugars, not by using sunlight’s energy, but by extracting energy from inorganic chemical compounds; hence, they are referred to as chemoautotrophs.
The importance of photosynthesis is not just that it can capture sunlight’s energy. A lizard sunning itself on a cold day can use the sun’s energy to warm up. Photosynthesis is vital because it evolved as a way to store the energy in solar radiation (the “photo-” part) as high-energy electrons in the carbon-carbon bonds of carbohydrate molecules (the “-synthesis” part). Those carbohydrates are the energy source that heterotrophs use to power the synthesis of ATP via respiration. Therefore, photosynthesis powers 99 percent of Earth’s ecosystems. When a top predator, such as a wolf, preys on a deer, the wolf is at the end of an energy path that went from nuclear reactions on the surface of the sun, to light, to photosynthesis, to vegetation, to deer, and finally to wolf.
Key Points
• Photosynthesis evolved as a way to store the energy in solar radiation as high-energy electrons in carbohydrate molecules.
• Plants, algae, and cyanobacteria, known as photoautotrophs, are the only organisms capable of performing photosynthesis.
• Heterotrophs, unable to produce their own food, rely on the carbohydrates produced by photosynthetic organisms for their energy needs.
Key Terms
• photosynthesis: the process by which plants and other photoautotrophs generate carbohydrates and oxygen from carbon dioxide, water, and light energy in chloroplasts
• photoautotroph: an organism that can synthesize its own food by using light as a source of energy
• chemoautotroph: a simple organism, such as a protozoan, that derives its energy from chemical processes rather than photosynthesis
8.02: Overview of Photosynthesis - Main Structures and Summary of Photosynthesis
Learning Objectives
• Describe the main structures involved in photosynthesis and recall the chemical equation that summarizes the process of photosynthesis
Overview of Photosynthesis
Photosynthesis is a multi-step process that requires sunlight, carbon dioxide, and water as substrates. It produces oxygen and glyceraldehyde-3-phosphate (G3P or GA3P), simple carbohydrate molecules that are high in energy and can subsequently be converted into glucose, sucrose, or other sugar molecules. These sugar molecules contain covalent bonds that store energy. Organisms break down these molecules to release energy for use in cellular work.
The energy from sunlight drives the reaction of carbon dioxide and water molecules to produce sugar and oxygen, as seen in the chemical equation for photosynthesis. Though the equation looks simple, it is carried out through many complex steps. Before learning the details of how photoautotrophs convert light energy into chemical energy, it is important to become familiar with the structures involved.
Photosynthesis and the Leaf
In plants, photosynthesis generally takes place in leaves, which consist of several layers of cells. The process of photosynthesis occurs in a middle layer called the mesophyll. The gas exchange of carbon dioxide and oxygen occurs through small, regulated openings called stomata (singular: stoma ), which also play a role in the plant’s regulation of water balance. The stomata are typically located on the underside of the leaf, which minimizes water loss. Each stoma is flanked by guard cells that regulate the opening and closing of the stomata by swelling or shrinking in response to osmotic changes.
Photosynthesis within the Chloroplast
In all autotrophic eukaryotes, photosynthesis takes place inside an organelle called a chloroplast. For plants, chloroplast-containing cells exist in the mesophyll. Chloroplasts have a double membrane envelope composed of an outer membrane and an inner membrane. Within the double membrane are stacked, disc-shaped structures called thylakoids.
Embedded in the thylakoid membrane is chlorophyll, a pigment that absorbs certain portions of the visible spectrum and captures energy from sunlight. Chlorophyll gives plants their green color and is responsible for the initial interaction between light and plant material, as well as numerous proteins that make up the electron transport chain. The thylakoid membrane encloses an internal space called the thylakoid lumen. A stack of thylakoids is called a granum, and the liquid-filled space surrounding the granum is the stroma or “bed.”
Key Points
• The chemical equation for photosynthesis is 6CO2+6H2O→C6H12O6+6O2.6CO2+6H2O→C6H12O6+6O2.
• In plants, the process of photosynthesis takes place in the mesophyll of the leaves, inside the chloroplasts.
• Chloroplasts contain disc-shaped structures called thylakoids, which contain the pigment chlorophyll.
• Chlorophyll absorbs certain portions of the visible spectrum and captures energy from sunlight.
Key Terms
• chloroplast: An organelle found in the cells of green plants and photosynthetic algae where photosynthesis takes place.
• mesophyll: A layer of cells that comprises most of the interior of the leaf between the upper and lower layers of epidermis.
• stoma: A pore in the leaf and stem epidermis that is used for gaseous exchange. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/08%3A_Photosynthesis/8.01%3A_Overview_of_Photosynthesis_-_The_Purpose_and_Process_of_Photosynthesis.txt |
Learning Objectives
• Distinguish between the two parts of photosynthesis
Light-Dependent Reactions
Just as the name implies, light-dependent reactions require sunlight. In the light-dependent reactions, energy from sunlight is absorbed by chlorophyll and converted into stored chemical energy, in the form of the electron carrier molecule NADPH (nicotinamide adenine dinucleotide phosphate) and the energy currency molecule ATP (adenosine triphosphate). The light-dependent reactions take place in the thylakoid membranes in the granum (stack of thylakoids), within the chloroplast.
Photosystems
The process that converts light energy into chemical energy takes place in a multi-protein complex called a photosystem. Two types of photosystems are embedded in the thylakoid membrane: photosystem II ( PSII) and photosystem I (PSI). Each photosystem plays a key role in capturing the energy from sunlight by exciting electrons. These energized electrons are transported by “energy carrier” molecules, which power the light-independent reactions.
Photosystems consist of a light-harvesting complex and a reaction center. Pigments in the light-harvesting complex pass light energy to two special chlorophyll a molecules in the reaction center. The light excites an electron from the chlorophyll a pair, which passes to the primary electron acceptor. The excited electron must then be replaced. In photosystem II, the electron comes from the splitting of water, which releases oxygen as a waste product. In photosystem I, the electron comes from the chloroplast electron transport chain.
The two photosystems oxidize different sources of the low-energy electron supply, deliver their energized electrons to different places, and respond to different wavelengths of light.
Light-Independent Reactions
In the light-independent reactions or Calvin cycle, the energized electrons from the light-dependent reactions provide the energy to form carbohydrates from carbon dioxide molecules. The light-independent reactions are sometimes called the Calvin cycle because of the cyclical nature of the process.
Although the light-independent reactions do not use light as a reactant (and as a result can take place at day or night), they require the products of the light-dependent reactions to function. The light-independent molecules depend on the energy carrier molecules, ATP and NADPH, to drive the construction of new carbohydrate molecules. After the energy is transferred, the energy carrier molecules return to the light-dependent reactions to obtain more energized electrons. In addition, several enzymes of the light-independent reactions are activated by light.
Key Points
• In light-dependent reactions, the energy from sunlight is absorbed by chlorophyll and converted into chemical energy in the form of electron carrier molecules like ATP and NADPH.
• Light energy is harnessed in Photosystems I and II, both of which are present in the thylakoid membranes of chloroplasts.
• In light-independent reactions (the Calvin cycle), carbohydrate molecules are assembled from carbon dioxide using the chemical energy harvested during the light-dependent reactions.
Key Terms
• photosystem: Either of two biochemical systems active in chloroplasts that are part of photosynthesis.
Photosynthesis takes place in two sequential stages:
1. The light-dependent reactions;
2. The light-independent reactions, or Calvin Cycle.
8.04: The Light-Dependent Reactions of Photosynthesis - Introduction to Light Energy
Learning Objectives
• Explain the difference between short and long wavelengths.
What Is Light Energy?
The sun emits an enormous amount of electromagnetic radiation (solar or light energy). Humans can see only a fraction of this energy, which is referred to as “visible light.” The manner in which solar energy travels is described as waves. Scientists can determine the amount of energy of a wave by measuring its wavelength, the distance between consecutive points of a wave, such as from crest to crest or from trough to trough.
Visible light constitutes only one of many types of electromagnetic radiation emitted from the sun and other stars. The electromagnetic spectrum is the range of all possible frequencies of radiation. The electromagnetic spectrum shows several types of electromagnetic radiation originating from the sun, including X-rays and ultraviolet (UV) rays. The higher-energy waves can penetrate tissues and damage cells and DNA, which explains why both X-rays and UV rays can be harmful to living organisms. Scientists differentiate the various types of radiant energy from the sun within the electromagnetic spectrum.The difference between wavelengths relates to the amount of energy carried by them.
Each type of electromagnetic radiation travels at a particular wavelength. The longer the wavelength, the less energy is carried. Short, tight waves carry the most energy. This may seem illogical, but think of it in terms of a person moving a heavy rope. It takes little effort by a person to move a rope in long, wide waves. To make a rope move in short, tight waves, a person would need to apply significantly more energy.
Key Points
• The amount of energy of a wave can be determined by measuring its wavelength, the distance between consecutive points of a wave.
• Visible light is a type of radiant energy within the electromagnetic spectrum; other types of electromagnetic radiation include UV, infrared, gamma, and radio rays as well as X-rays.
• The difference between wavelengths relates to the amount of energy carried by them; short, tight waves carry more energy than long, wide waves.
Key Terms
• electromagnetic spectrum: the entire range of wavelengths of all known radiations consisting of oscillating electric and magnetic fields, including gamma rays, visible light, infrared, radio waves, and X-rays
• wavelength: the length of a single cycle of a wave, as measured by the distance between one peak or trough of a wave and the next; it corresponds to the velocity of the wave divided by its frequency
• visible light: the part of the electromagnetic spectrum, between infrared and ultraviolet, that is visible to the human eye | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/08%3A_Photosynthesis/8.03%3A_Overview_of_Photosynthesis_-_The_Two_Parts_of_Photosynthesis.txt |
Learning Objectives
• Differentiate between chlorophyll and carotenoids.
Absorption of Light
Light energy initiates the process of photosynthesis when pigments absorb the light. Organic pigments have a narrow range of energy levels that they can absorb. Energy levels lower than those represented by red light are insufficient to raise an orbital electron to an excited, or quantum, state. Energy levels higher than those in blue light will physically tear the molecules apart, a process called bleaching. For example, retinal pigments can only “see” (absorb) 700 nm to 400 nm light; this is visible light. For the same reasons, plant pigment molecules absorb only light in the wavelength range of 700 nm to 400 nm; plant physiologists refer to this range for plants as photosynthetically-active radiation.
The visible light seen by humans as the color white light actually exists in a rainbow of colors in the electromagnetic spectrum, with violet and blue having shorter wavelengths and, thus, higher energy. At the other end of the spectrum, toward red, the wavelengths are longer and have lower energy.
Understanding Pigments
Different kinds of pigments exist, each of which has evolved to absorb only certain wavelengths or colors of visible light. Pigments reflect or transmit the wavelengths they cannot absorb, making them appear in the corresponding color.
Chlorophylls and carotenoids are the two major classes of photosynthetic pigments found in plants and algae; each class has multiple types of pigment molecules. There are five major chlorophylls: a, b, c and d, along with a related molecule found in prokaryotes called bacteriochlorophyll.
With dozens of different forms, carotenoids are a much larger group of pigments. The carotenoids found in fruit, such as the red of tomato (lycopene), the yellow of corn seeds (zeaxanthin), or the orange of an orange peel (β-carotene), are used to attract seed-dispersing organisms. In photosynthesis, carotenoids function as photosynthetic pigments that are very efficient molecules for the disposal of excess energy. When a leaf is exposed to full sun, the light-dependent reactions are required to process an enormous amount of energy; if that energy is not handled properly, it can do significant damage. Therefore, many carotenoids are stored in the thylakoid membrane to absorb excess energy and safely release that energy as heat.
Each type of pigment can be identified by the specific pattern of wavelengths it absorbs from visible light, which is the absorption spectrum. Chlorophyll a absorbs light in the blue-violet region, while chlorophyll b absorbs red-blue light. Neither a or b absorb green light; because green is reflected or transmitted, chlorophyll appears green. Carotenoids absorb light in the blue-green and violet region and reflect the longer yellow, red, and orange wavelengths.
Many photosynthetic organisms have a mixture of pigments. In this way organisms can absorb energy from a wider range of wavelengths. Not all photosynthetic organisms have full access to sunlight. Some organisms grow underwater where light intensity and quality decrease and change with depth. Other organisms grow in competition for light. Plants on the rainforest floor must be able to absorb any light that comes through because the taller trees absorb most of the sunlight and scatter the remaining solar radiation
When studying a photosynthetic organism, scientists can determine the types of pigments present by using a spectrophotometer. These instruments can differentiate which wavelengths of light a substance can absorb. Spectrophotometers measure transmitted light and compute its absorption. By extracting pigments from leaves and placing these samples into a spectrophotometer, scientists can identify which wavelengths of light an organism can absorb.
Key Points
• Plant pigment molecules absorb only light in the wavelength range of 700 nm to 400 nm; this range is referred to as photosynthetically-active radiation.
• Violet and blue have the shortest wavelengths and the most energy, whereas red has the longest wavelengths and carries the least amount of energy.
• Pigments reflect or transmit the wavelengths they cannot absorb, making them appear in the corresponding color.
• Chorophylls and carotenoids are the major pigments in plants; while there are dozens of carotenoids, there are only five important chorophylls: a, b, c, d, and bacteriochlorophyll.
• Chlorophyll a absorbs light in the blue-violet region, chlorophyll b absorbs red-blue light, and both a and b reflect green light (which is why chlorophyll appears green).
• Carotenoids absorb light in the blue-green and violet region and reflect the longer yellow, red, and orange wavelengths; these pigments also dispose excess energy out of the cell.
Key Terms
• chlorophyll: Any of a group of green pigments that are found in the chloroplasts of plants and in other photosynthetic organisms such as cyanobacteria.
• carotenoid: Any of a class of yellow to red plant pigments including the carotenes and xanthophylls.
• spectrophotometer: An instrument used to measure the intensity of electromagnetic radiation at different wavelengths. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/08%3A_Photosynthesis/8.05%3A_The_Light-Dependent_Reactions_of_Photosynthesis_-_Absorption_of_Light.txt |
Learning Objectives
• Describe how light energy is converted into ATP and NADPH.
How Light-Dependent Reactions Work
The overall function of light-dependent reactions, the first stage of photosynthesis, is to convert solar energy into chemical energy in the form of NADPH and ATP, which are used in light-independent reactions and fuel the assembly of sugar molecules. Protein complexes and pigment molecules work together to produce NADPH and ATP.
Producing Chemical Energy
Light energy is converted into chemical energy in a multiprotein complex called a photosystem. Two types of photosystems, photosystem I (PSI) and photosystem II (PSII), are found in the thylakoid membrane inside the chloroplast. Each photosystem consists of multiple antenna proteins that contain a mixture of 300–400 chlorophyll a and b molecules, as well as other pigments like carotenoids. Cytochrome b6f complex and ATP synthase are also major protein complexes in the thylakoid membrane that work with the photosystems to create ATP and NADPH.
The two photosystems absorb light energy through proteins containing pigments, such as chlorophyll. The light-dependent reactions begin in photosystem II. In PSII, energy from sunlight is used to split water, which releases two electrons, two hydrogen atoms, and one oxygen atom. When a chlorophyll a molecule within the reaction center of PSII absorbs a photon, the electron in this molecule attains a higher energy level. Because this state of an electron is very unstable, the electron is transferred to another molecule creating a chain of redox reactions called an electron transport chain (ETC). The electron flow goes from PSII to cytochrome b6f to PSI; as electrons move between these two photosystems, they lose energy. Because the electrons have lost energy prior to their arrival at PSI, they must be re-energized by PSI. Therefore, another photon is absorbed by the PSI antenna. That energy is transmitted to the PSI reaction center. This reaction center, known as P700, is oxidized and sends a high-energy electron to reduce NADP+ to NADPH. This process illustrates oxygenic photosynthesis, wherein the first electron donor is water and oxygen is created as a waste product.
Cytochrome b6f and ATP synthase work together to create ATP. This process, called photophosphorylation, occurs in two different ways. In non-cyclic photophosphorylation, cytochrome b6f uses the energy of electrons from PSII to pump hydrogen ions from the lumen (an area of high concentration) to the stroma (an area of low concentration). The energy released by the hydrogen ion stream allows ATP synthase to attach a third phosphate group to ADP, which forms ATP. This flow of hydrogen ions through ATP synthase is called chemiosmosis because the ions move from an area of high to an area of low concentration through a semi-permeable structure. In cyclic photophosphorylation, cytochrome b6f uses the energy of electrons from both PSII and PSI to create more ATP and to stop the production of NADPH. Cyclic phosphorylation is important to maintain the right proportions of NADPH and ATP, which will carry out light-independent reactions later on.
The net-reaction of all light-dependent reactions in oxygenic photosynthesis is: 2H2O + 2NADP+ + 3ADP + 3Pi → O2 + 2NADPH + 3ATP
Key Points
• Light energy splits water and extracts electrons in photosystem II (PSII); then electrons are moved from PSII to cytochrome b6f to photosystem I (PSI) and reduce in energy.
• Electrons are re-energized in PSI and those high energy electrons reduce NADP+ to NADPH.
• In non-cyclic photophosphorylation, cytochrome b6f uses the energy of electrons from PSII to pump hydrogen ions from the lumen to the stroma; this energy allows ATP synthase to attach a third phosphate group to ADP, which forms ATP.
• In cyclic photophosphorylation, cytochrome b6f uses the energy of electrons from both PSII and PSI to create more ATP and to stop the production of NADPH, maintaining the right proportions of NADPH and ATP.
Key Terms
• photosystem: Either of two biochemical systems, active in chloroplasts, that are part of photosynthesis.
• photophosphorylation: The addition of a phosphate (PO43-) group to a protein or other organic molecule by photosynthesis.
• chemiosmosis: The movement of ions across a selectively permeable membrane, down their electrochemical gradient.
Contributions and Attributions
• visible light. Provided by: Wiktionary. Located at: http://en.wiktionary.org/wiki/visible_light. License: CC BY-SA: Attribution-ShareAlike
• OpenStax College, Biology. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44448/latest...ol11448/latest. License: CC BY: Attribution
• Boundless. Provided by: Boundless Learning. Located at: www.boundless.com//biology/de...netic-spectrum. License: CC BY-SA: Attribution-ShareAlike
• wavelength. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/wavelength. License: CC BY-SA: Attribution-ShareAlike
• OpenStax College, The Light-Dependent Reactions of Photosynthesis. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44448/latest...e_08_02_03.jpg. License: CC BY: Attribution
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• spectrophotometer. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/spectrophotometer. License: CC BY-SA: Attribution-ShareAlike
• carotenoid. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/carotenoid. License: CC BY-SA: Attribution-ShareAlike
• chlorophyll. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/chlorophyll. License: CC BY-SA: Attribution-ShareAlike
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• photosystem. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/photosystem. License: CC BY-SA: Attribution-ShareAlike
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Learning Objectives
• Compare C4 and CAM photosynthesis
Photosynthesis in desert plants has evolved adaptations that conserve water. In harsh, dry heat, every drop of water must be used to survive. Because stomata must open to allow for the uptake of CO2, water escapes from the leaf during active photosynthesis. Desert plants have evolved processes to conserve water and deal with harsh conditions. A more efficient use of CO2 allows plants to adapt to living with less water.
Some plants such as cacti can prepare materials for photosynthesis during the night by a temporary carbon fixation and storage process, because opening the stomata at this time conserves water due to cooler temperatures. In addition, cacti have evolved the ability to carry out low levels of photosynthesis without opening stomata at all, a mechanism for surviving extremely dry periods.
CAM Photosynthesis
Xerophytes, such as cacti and most succulents, also use
phosphoenolpyruvate (PEP) carboxylase to capture carbon dioxide in a process called crassulacean acid metabolism (CAM). In contrast to C4 metabolism, which physically separates the CO2 fixation to PEP from the Calvin cycle, CAM temporally separates these two processes.
CAM plants have a different leaf anatomy from C3 plants, and fix the CO2 at night, when their stomata are open. CAM plants store the CO2 mostly in the form of malic acid via carboxylation of phosphoenolpyruvate to oxaloacetate, which is then reduced to malate. Decarboxylation of malate during the day releases CO2 inside the leaves, thus allowing carbon fixation to 3-phosphoglycerate by RuBisCO. Sixteen thousand species of plants use CAM.
C4 Carbon Fixation
The C4 pathway bears resemblance to CAM; both act to concentrate CO2 around RuBisCO, thereby increasing its efficiency. CAM concentrates it temporally, providing CO2 during the day and not at night, when respiration is the dominant reaction.
C4 plants, in contrast, concentrate CO2 spatially, with a RuBisCO reaction centre in a “bundle sheath cell” that is inundated with CO2. Due to the inactivity required by the CAM mechanism, C4 carbon fixation has a greater efficiency in terms of PGA synthesis.
Cross section of maize, a C4 plant
Cross section of a C4 plant, specifically of a maize leaf. Drawing based on microscopic images courtesy of Cambridge University Plant Sciences Department.
C4 plants can produce more sugar than C3 plants in conditions of high light and temperature. Many important crop plants are C4 plants, including maize, sorghum, sugarcane, and millet. Plants that do not use PEP-carboxylase in carbon fixation are called C3 plants because the primary carboxylation reaction, catalyzed by RuBisCO, produces the three-carbon 3-phosphoglyceric acids directly in the Calvin-Benson cycle. Over 90% of plants use C3 carbon fixation, compared to 3% that use C4 carbon fixation; however, the evolution of C4 in over 60 plant lineages makes it a striking example of convergent evolution.
Key Points
• The process of photosynthesis in desert plants has evolved mechanisms to conserve water.
• Plants that use crassulacean acid metabolism (CAM) photosynthesis fix CO2 at night, when their stomata are open.
• Plants that use C4 carbon fixation concentrate carbon dioxide spatially, using “bundle sheath cells” which are inundated with CO2.
Key Terms
• crassulacean acid metabolism: A carbon fixation pathway that evolved in some plants as an adaptation to arid conditions, in which the stomata in the leaves remain shut during the day to reduce evapotranspiration, but open at night to collect carbon dioxide (CO2).
• C4 carbon fixation: A form of photosynthesis in which plants concentrate CO2 spatially, with a RuBisCO reaction centre in a “bundle sheath cell” that is inundated with CO2 | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/08%3A_Photosynthesis/8.07%3A_The_Light-Independent_Reactions_of_Photosynthesis_-_AM_and_C4_Photosynthesis.txt |
Learning Objectives
• Describe the Calvin Cycle
The Calvin Cycle
In plants, carbon dioxide (CO2) enters the leaves through stomata, where it diffuses over short distances through intercellular spaces until it reaches the mesophyll cells. Once in the mesophyll cells, CO2 diffuses into the stroma of the chloroplast, the site of light-independent reactions of photosynthesis. These reactions actually have several names associated with them. Other names for light-independent reactions include the Calvin cycle, the Calvin-Benson cycle, and dark reactions. The most outdated name is dark reactions, which can be misleading because it implies incorrectly that the reaction only occurs at night or is independent of light, which is why most scientists and instructors no longer use it.
The light-independent reactions of the Calvin cycle can be organized into three basic stages: fixation, reduction, and regeneration.
Stage 1: Fixation
In the stroma, in addition to CO2,two other components are present to initiate the light-independent reactions: an enzyme called ribulose bisphosphate carboxylase (RuBisCO) and three molecules of ribulose bisphosphate (RuBP). RuBP has five atoms of carbon, flanked by two phosphates. RuBisCO catalyzes a reaction between CO2 and RuBP. For each CO2 molecule that reacts with one RuBP, two molecules of 3-phosphoglyceric acid (3-PGA) form. 3-PGA has three carbons and one phosphate. Each turn of the cycle involves only one RuBP and one carbon dioxide and forms two molecules of 3-PGA. The number of carbon atoms remains the same, as the atoms move to form new bonds during the reactions (3 atoms from 3CO2 + 15 atoms from 3RuBP = 18 atoms in 3 atoms of 3-PGA). This process is called carbon fixation because CO2 is “fixed” from an inorganic form into organic molecules.
Stage 2: Reduction
ATP and NADPH are used to convert the six molecules of 3-PGA into six molecules of a chemical called glyceraldehyde 3-phosphate (G3P). This is a reduction reaction because it involves the gain of electrons by 3-PGA. Recall that a reduction is the gain of an electron by an atom or molecule. Six molecules of both ATP and NADPH are used. For ATP, energy is released with the loss of the terminal phosphate atom, converting it to ADP; for NADPH, both energy and a hydrogen atom are lost, converting it into NADP+. Both of these molecules return to the nearby light-dependent reactions to be reused and reenergized.
Stage 3: Regeneration
At this point, only one of the G3P molecules leaves the Calvin cycle and is sent to the cytoplasm to contribute to the formation of other compounds needed by the plant. Because the G3P exported from the chloroplast has three carbon atoms, it takes three “turns” of the Calvin cycle to fix enough net carbon to export one G3P. But each turn makes two G3Ps, thus three turns make six G3Ps. One is exported while the remaining five G3P molecules remain in the cycle and are used to regenerate RuBP, which enables the system to prepare for more CO2 to be fixed. Three more molecules of ATP are used in these regeneration reactions.
Key Points
• The Calvin cycle refers to the light-independent reactions in photosynthesis that take place in three key steps.
• Although the Calvin Cycle is not directly dependent on light, it is indirectly dependent on light since the necessary energy carriers ( ATP and NADPH) are products of light-dependent reactions.
• In fixation, the first stage of the Calvin cycle, light-independent reactions are initiated; CO2 is fixed from an inorganic to an organic molecule.
• In the second stage, ATP and NADPH are used to reduce 3-PGA into G3P; then ATP and NADPH are converted to ADP and NADP+, respectively.
• In the last stage of the Calvin Cycle, RuBP is regenerated, which enables the system to prepare for more CO2 to be fixed.
Key Terms
• light-independent reaction: chemical reactions during photosynthesis that convert carbon dioxide and other compounds into glucose, taking place in the stroma
• rubisco: (ribulose bisphosphate carboxylase) a plant enzyme which catalyzes the fixing of atmospheric carbon dioxide during photosynthesis by catalyzing the reaction between carbon dioxide and RuBP
• ribulose bisphosphate: an organic substance that is involved in photosynthesis, reacts with carbon dioxide to form 3-PGA
8.09: The Light-Independent Reactions of Photosynthesis - The Carbon Cycle
Learning Objectives
• Describe the importance of the carbon cycle
The Carbon Cycle
Whether the organism is a bacterium, plant, or animal, all living things access energy by breaking down carbohydrate molecules. But if plants make carbohydrate molecules, why would they need to break them down, especially when it has been shown that the gas organisms release as a “waste product” (CO2) acts as a substrate for the formation of more food in photosynthesis? Living things need energy to perform life functions. In addition, an organism can either make its own food or eat another organism; either way, the food still needs to be broken down. Finally, in the process of breaking down food, called cellular respiration, heterotrophs release needed energy and produce “waste” in the form of CO2 gas.
In nature, there is no such thing as waste. Every single atom of matter and energy is conserved, recycling over and over, infinitely. Substances change form or move from one type of molecule to another, but their constituent atoms never disappear.
CO2 is no more a form of waste than oxygen is wasteful to photosynthesis. Both are byproducts of reactions that move on to other reactions. Photosynthesis absorbs light energy to build carbohydrates in chloroplasts, and aerobic cellular respiration releases energy by using oxygen to metabolize carbohydrates in the cytoplasm and mitochondria. Photosynthesis consumes carbon dioxide and produces oxygen. Aerobic respiration consumes oxygen and produces carbon dioxide. Both processes use electron transport chains to capture the energy necessary to drive other reactions. These two powerhouse processes, photosynthesis and cellular respiration, function in biological, cyclical harmony to allow organisms to access life-sustaining energy that originates millions of miles away in the sun.
Key Points
• Every single atom of energy is conserved by changing form or moving from one type of energy to another, so waste does not exist in nature.
• Photosynthesis absorbs light energy to build carbohydrates, and aerobic cellular respiration releases energy by using oxygen to metabolize carbohydrates.
• Photosynthesis consumes carbon dioxide and produces oxygen, and aerobic respiration consumes oxygen and produces carbon dioxide.
• Both photosynthesis and cellular respiration use electron transport chains to capture the energy necessary to drive other reactions.
Key Terms
• heterotroph: an organism that requires an external supply of energy in the form of food, as it cannot synthesize its own
• cellular respiration: the set of the metabolic reactions and processes that take place in the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate (ATP)
• aerobic: living or occurring only in the presence of oxygen | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/08%3A_Photosynthesis/8.08%3A_The_Light-Independent_Reactions_of_Photosynthesis_-_The_Calvin_Cycle.txt |
Learning Objectives
• Explain the importance of cell communication
Introduction: Signaling Molecules and Cellular Receptors
Imagine what life would be like if you and the people around you could not communicate. You would not be able to express your wishes to others, nor could you ask questions to find out more about your environment. Social organization is dependent on communication between the individuals that comprise that society; without communication, society would fall apart.
As with people, it is vital for individual cells to be able to interact with their environment. This is true whether a cell is growing by itself in a pond or is one of many cells that form a larger organism. In order to properly respond to external stimuli, cells have developed complex mechanisms of communication that can receive a message, transfer the information across the plasma membrane, and then produce changes within the cell in response to the message.
In multicellular organisms, cells send and receive chemical messages constantly to coordinate the actions of distant organs, tissues, and cells. The ability to send messages quickly and efficiently enables cells to coordinate and fine-tune their functions.
While the necessity for cellular communication in larger organisms seems obvious, even single-celled organisms communicate with each other. Yeast cells signal each other to aid mating. Some forms of bacteria coordinate their actions in order to form large complexes called biofilms or to organize the production of toxins to remove competing organisms. The ability of cells to communicate through chemical signals originated in single cells and was essential for the evolution of multicellular organisms. The efficient and error-free function of communication systems is vital for all forms of life.
Key Points
• The ability of cells to communicate through chemical signals originated in single cells and was essential for the evolution of multicellular organisms.
• In multicellular organisms, cells send and receive chemical messages constantly to coordinate the actions of distant organs, tissues, and cells.
• Cells can receive a message, transfer the information across the plasma membrane, and then produce changes within the cell in response to the message.
• Single-celled organisms, like yeast and bacteria, communicate with each other to aid in mating and coordination.
• Cellular communication has developed as a means to communicate with the environment, produce biological changes, and, if necessary, ensure survival.
Key Terms
• biofilm: a thin film of mucus created by and containing a colony of bacteria and other microorganisms
9.02: Signaling Molecules and Cellular Receptors - Forms of Signaling
Learning Objectives
• Describe four types of signaling found in multicellular organisms
Forms of Signaling
There are four categories of chemical signaling found in multicellular organisms: paracrine signaling, endocrine signaling, autocrine signaling, and direct signaling across gap junctions. The main difference between the different categories of signaling is the distance that the signal travels through the organism to reach the target cell. It is also important to note that not all cells are affected by the same signals.
Paracrine Signaling
Signals that act locally between cells that are close together are called paracrine signals. Paracrine signals move by diffusion through the extracellular matrix. These types of signals usually elicit quick responses that last only a short amount of time. In order to keep the response localized, paracrine ligand molecules are normally quickly degraded by enzymes or removed by neighboring cells. Removing the signals will reestablish the concentration gradient for the signal, allowing them to quickly diffuse through the intracellular space if released again.
One example of paracrine signaling is the transfer of signals across synapses between nerve cells. A nerve cell consists of a cell body, several short, branched extensions called dendrites that receive stimuli, and a long extension called an axon, which transmits signals to other nerve cells or muscle cells. The junction between nerve cells where signal transmission occurs is called a synapse. A synaptic signal is a chemical signal that travels between nerve cells. Signals within the nerve cells are propagated by fast-moving electrical impulses. When these impulses reach the end of the axon, the signal continues on to a dendrite of the next cell by the release of chemical ligands called neurotransmitters by the presynaptic cell (the cell emitting the signal). The neurotransmitters are transported across the very small distances between nerve cells, which are called chemical synapses. The small distance between nerve cells allows the signal to travel quickly; this enables an immediate response.
Endocrine Signaling
Signals from distant cells are called endocrine signals; they originate from endocrine cells. In the body, many endocrine cells are located in endocrine glands, such as the thyroid gland, the hypothalamus, and the pituitary gland. These types of signals usually produce a slower response, but have a longer-lasting effect. The ligands released in endocrine signaling are called hormones, signaling molecules that are produced in one part of the body, but affect other body regions some distance away.
Hormones travel the large distances between endocrine cells and their target cells via the bloodstream, which is a relatively slow way to move throughout the body. Because of their form of transport, hormones get diluted and are present in low concentrations when they act on their target cells. This is different from paracrine signaling in which local concentrations of ligands can be very high.
Autocrine Signaling
Autocrine signals are produced by signaling cells that can also bind to the ligand that is released. This means the signaling cell and the target cell can be the same or a similar cell (the prefix auto- means self, a reminder that the signaling cell sends a signal to itself). This type of signaling often occurs during the early development of an organism to ensure that cells develop into the correct tissues and take on the proper function. Autocrine signaling also regulates pain sensation and inflammatory responses. Further, if a cell is infected with a virus, the cell can signal itself to undergo programmed cell death, killing the virus in the process. In some cases, neighboring cells of the same type are also influenced by the released ligand. In embryological development, this process of stimulating a group of neighboring cells may help to direct the differentiation of identical cells into the same cell type, thus ensuring the proper developmental outcome.
Direct Signaling Across Gap Junctions
Gap junctions in animals and plasmodesmata in plants are connections between the plasma membranes of neighboring cells. These water-filled channels allow small signaling molecules, called intracellular mediators, to diffuse between the two cells. Small molecules, such as calcium ions (Ca2+), are able to move between cells, but large molecules, like proteins and DNA, cannot fit through the channels. The specificity of the channels ensures that the cells remain independent, but can quickly and easily transmit signals. The transfer of signaling molecules communicates the current state of the cell that is directly next to the target cell; this allows a group of cells to coordinate their response to a signal that only one of them may have received. In plants, plasmodesmata are ubiquitous, making the entire plant into a giant communication network.
Key Points
• Cells communicate via various types of signaling that allow chemicals to travel to target sites in order to elicit a response.
• Paracrine signaling occurs between local cells where the signals elicit quick responses and last only a short amount of time due to the degradation of the paracrine ligands.
• Endocrine signaling occurs between distant cells and is mediated by hormones released from specific endocrine cells that travel to target cells, producing a slower, long-lasting response.
• Autocrine signals are produced by signaling cells that can also bind to the ligand that is released, which means the signaling cell and the target cell can be the same or a similar cell.
• Direct signaling can occur by transferring signaling molecules across gap junctions between neighboring cells.
Key Terms
• endocrine signaling: signals from distant cells that originate from endocrine cells, usually producing a slow response, but having a long-lasting effect
• autocrine signaling: produced by signaling cells that can also bind to the ligand that is released: the signaling cell and the target cell can be the same or a similar cell (prefix auto- means self)
• paracrine signaling: a form of cell signaling in which the target cell is near (para = near) the signal-releasing cell | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/09%3A_Cell_Communication/9.01%3A_Signaling_Molecules_and_Cellular_Receptors_-_Signaling_Molecules_and_Cellular_Receptors.txt |
Learning Objectives
• Compare internal receptors with cell-surface receptors
Types of Receptors
Receptors are protein molecules in the target cell or on its surface that bind ligands. There are two types of receptors: internal receptors and cell-surface receptors.
Internal receptors
Internal receptors, also known as intracellular or cytoplasmic receptors, are found in the cytoplasm of the cell and respond to hydrophobic ligand molecules that are able to travel across the plasma membrane. Once inside the cell, many of these molecules bind to proteins that act as regulators of mRNA synthesis to mediate gene expression. Gene expression is the cellular process of transforming the information in a cell’s DNA into a sequence of amino acids that ultimately forms a protein. When the ligand binds to the internal receptor, a conformational change exposes a DNA-binding site on the protein. The ligand-receptor complex moves into the nucleus, binds to specific regulatory regions of the chromosomal DNA, and promotes the initiation of transcription. Internal receptors can directly influence gene expression without having to pass the signal on to other receptors or messengers.
Cell-Surface Receptors
Cell-surface receptors, also known as transmembrane receptors, are cell surface, membrane-anchored, or integral proteins that bind to external ligand molecules. This type of receptor spans the plasma membrane and performs signal transduction, converting an extracellular signal into an intracellular signal. Ligands that interact with cell-surface receptors do not have to enter the cell that they affect. Cell-surface receptors are also called cell-specific proteins or markers because they are specific to individual cell types.
Each cell-surface receptor has three main components: an external ligand-binding domain (extracellular domain), a hydrophobic membrane-spanning region, and an intracellular domain inside the cell. The size and extent of each of these domains vary widely, depending on the type of receptor.
Cell-surface receptors are involved in most of the signaling in multicellular organisms. There are three general categories of cell-surface receptors: ion channel-linked receptors, G-protein-linked receptors, and enzyme-linked receptors.
Ion Channel-Linked Receptors
Ion channel-linked receptors bind a ligand and open a channel through the membrane that allows specific ions to pass through. To form a channel, this type of cell-surface receptor has an extensive membrane-spanning region. In order to interact with the phospholipid fatty acid tails that form the center of the plasma membrane, many of the amino acids in the membrane-spanning region are hydrophobic in nature. Conversely, the amino acids that line the inside of the channel are hydrophilic to allow for the passage of water or ions. When a ligand binds to the extracellular region of the channel, there is a conformational change in the protein’s structure that allows ions such as sodium, calcium, magnesium, and hydrogen to pass through.
G-Protein Linked Receptors
G-protein-linked receptors bind a ligand and activate a membrane protein called a G-protein. The activated G-protein then interacts with either an ion channel or an enzyme in the membrane. All G-protein-linked receptors have seven transmembrane domains, but each receptor has its own specific extracellular domain and G-protein-binding site.
Cell signaling using G-protein-linked receptors occurs as a cyclic series of events. Before the ligand binds, the inactive G-protein can bind to a newly-revealed site on the receptor specific for its binding. Once the G-protein binds to the receptor, the resultant shape change activates the G-protein, which releases GDP and picks up GTP. The subunits of the G-protein then split into the α subunit and the β subunit. One or both of these G-protein fragments may be able to activate other proteins as a result. Later, the GTP on the active α subunit of the G-protein is hydrolyzed to GDP and the β subunit is deactivated. The subunits reassociate to form the inactive G-protein, and the cycle starts over.
Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors with intracellular domains that are associated with an enzyme. In some cases, the intracellular domain of the receptor itself is an enzyme or the enzyme-linked receptor has an intracellular domain that interacts directly with an enzyme. The enzyme-linked receptors normally have large extracellular and intracellular domains, but the membrane-spanning region consists of a single alpha-helical region of the peptide strand. When a ligand binds to the extracellular domain, a signal is transferred through the membrane and activates the enzyme, which sets off a chain of events within the cell that eventually leads to a response. An example of this type of enzyme-linked receptor is the tyrosine kinase receptor. The tyrosine kinase receptor transfers phosphate groups to tyrosine molecules. Signaling molecules bind to the extracellular domain of two nearby tyrosine kinase receptors, which then dimerize. Phosphates are then added to tyrosine residues on the intracellular domain of the receptors and can then transmit the signal to the next messenger within the cytoplasm.
Key Points
• Intracellular receptors are located in the cytoplasm of the cell and are activated by hydrophobic ligand molecules that can pass through the plasma membrane.
• Cell-surface receptors bind to an external ligand molecule and convert an extracellular signal into an intracellular signal.
• Three general categories of cell-surface receptors include: ion -channel, G- protein, and enzyme -linked protein receptors.
• Ion channel -linked receptors bind a ligand and open a channel through the membrane that allows specific ions to pass through.
• G-protein-linked receptors bind a ligand and activate a membrane protein called a G-protein, which then interacts with either an ion channel or an enzyme in the membrane.
• Enzyme-linked receptors are cell-surface receptors with intracellular domains that are associated with an enzyme.
Key Terms
• integral protein: a protein molecule (or assembly of proteins) that is permanently attached to the biological membrane
• transcription: the synthesis of RNA under the direction of DNA | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/09%3A_Cell_Communication/9.03%3A_Signaling_Molecules_and_Cellular_Receptors_-_Types_of_Receptors.txt |
Learning Objectives
• Compare and contrast the different types of signaling molecules: hydrophobic, water-soluble, and gas ligands
Signaling Molecules
Produced by signaling cells and the subsequent binding to receptors in target cells, ligands act as chemical signals that travel to the target cells to coordinate responses. The types of molecules that serve as ligands are incredibly varied and range from small proteins to small ions like calcium (Ca2+).
Small Hydrophobic Ligands
Small hydrophobic ligands can directly diffuse through the plasma membrane and interact with internal receptors. Important members of this class of ligands are the steroid hormones. Steroids are lipids that have a hydrocarbon skeleton with four fused rings; different steroids have different functional groups attached to the carbon skeleton. Steroid hormones include the female sex hormone, estradiol, which is a type of estrogen; the male sex hormone, testosterone; and cholesterol, which is an important structural component of biological membranes and a precursor of steriod hormones. Other hydrophobic hormones include thyroid hormones and vitamin D. In order to be soluble in blood, hydrophobic ligands must bind to carrier proteins while they are being transported through the bloodstream.
Water-Soluble Ligands
Water-soluble ligands are polar and, therefore, cannot pass through the plasma membrane unaided; sometimes, they are too large to pass through the membrane at all. Instead, most water-soluble ligands bind to the extracellular domain of cell-surface receptors. Cell-surface receptors include: ion-channel, G-protein, and enzyme-linked protein receptors. The binding of these ligands to these receptors results in a series of cellular changes. These water soluble ligands are quite diverse and include small molecules, peptides, and proteins.
Other Ligands
Nitric oxide (NO) is a gas that also acts as a ligand. It is able to diffuse directly across the plasma membrane; one of its roles is to interact with receptors in smooth muscle and induce relaxation of the tissue. NO has a very short half-life; therefore, it only functions over short distances. Nitroglycerin, a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate (expand), thus restoring blood flow to the heart.
Key Points
• Signaling molecules can range from small proteins to small ions and can be hydrophobic, water-soluble, or even a gas.
• Hydrophobic signaling molecules ( ligands ) can diffuse through the plasma membrane and bind to internal receptors.
• Water-soluble ligands are unable to pass freely through the plasma membrane due to their polarity and must bind to an extracellular domain of a cell -surface receptor.
• Other types of ligands can include gases, such as nitric oxide, which can freely diffuse through the plasma membrane and bind to internal receptors.
Key Terms
• ligand: an ion, molecule, or functional group that binds to another chemical entity to form a larger complex
• hydrophobic: lacking an affinity for water; unable to absorb, or be wetted by water
9.05: Propagation of the Cellular Signal - Binding Initiates a Signaling Pathway
Learning Objectives
• Recognize the relationship between a ligand’s structure and its mechanism of action.
Cell-surface receptors, also known as transmembrane receptors, are membrane-anchored (integral) proteins that bind to external ligand molecules. This type of receptor spans the plasma membrane and performs signal transduction in which an extracellular signal is converted into an intracellular signal. Ligands that interact with cell-surface receptors do not have to enter the cell that they affect. Cell-surface receptors are also called cell-specific proteins or markers because they are specific to individual cell types. Each cell-surface receptor has three main components: an external ligand-binding domain, a hydrophobic membrane-spanning region, and an intracellular domain inside the cell. The ligand-binding domain is also called the extracellular domain. The size and extent of each of these domains vary widely, depending on the type of receptor. Cell-surface receptors are involved in most of the signaling in multicellular organisms.
There are three general categories of cell-surface receptors: ion channel-linked receptors, G-protein-linked receptors, and enzyme-linked receptors.
1. Ion channel-linked receptors bind a ligand and open a channel through the membrane that allows specific ions to pass through. To form a channel, this type of cell-surface receptor has an extensive membrane-spanning region. When a ligand binds to the extracellular region of the channel, there is a conformational change in the protein’s structure that allows ions such as sodium, calcium, magnesium, and hydrogen to pass through.
2. G-protein-linked receptors bind a ligand and activate a membrane protein called a G-protein. The activated G-protein then interacts with either an ion channel or an enzyme in the membrane. All G-protein-linked receptors have seven transmembrane domains, but each receptor has its own specific extracellular domain and G-protein-binding site.
3. Enzyme-linked receptors are cell-surface receptors with intracellular domains that are associated with an enzyme. In some cases, the intracellular domain of the receptor itself is an enzyme. Other enzyme-linked receptors have a small intracellular domain that interacts directly with an enzyme. When a ligand binds to the extracellular domain, a signal is transferred through the membrane, activating the enzyme. Activation of the enzyme sets off a chain of events within the cell that eventually leads to a response.
After the ligand binds to the cell-surface receptor, the activation of the receptor’s intracellular components sets off a chain of events that is called a signaling pathway or a signaling cascade. In a signaling pathway, second messengers, enzymes, and activated proteins interact with specific proteins, which are in turn activated in a chain reaction that eventually leads to a change in the cell’s environment. The events in the cascade occur in a series, much like a current flows in a river. Interactions that occur before a certain point are defined as upstream events; events after that point are called downstream events.
Signaling pathways can get very complicated very quickly because most cellular proteins can affect different downstream events, depending on the conditions within the cell. A single pathway can branch off toward different endpoints based on the interplay between two or more signaling pathways. The same ligands are often used to initiate different signals in different cell types. This variation in response is due to differences in protein expression in different cell types. Another complicating element is signal integration of the pathways in which signals from two or more different cell-surface receptors merge to activate the same response in the cell. This process can ensure that multiple external requirements are met before a cell commits to a specific response.
The effects of extracellular signals can also be amplified by enzymatic cascades. At the initiation of the signal, a single ligand binds to a single receptor. However, activation of a receptor-linked enzyme can activate many copies of a component of the signaling cascade, which amplifies the signal.
Key Points
• Signaling pathways can be complicated since most cellular proteins can affect different downstream events.
• Cell -surface receptors are integral in signaling pathways.
• Ion channel -linked receptors open a channel once a ligand binds allowing specific ions to pass through the membrane.
• G-protein-linked receptors activate a membrane protein called a G-protein once a ligand binds.
• Enzyme -linked receptors are cell-surface receptors with intracellular domains.
Key Terms
• ligand: an ion, molecule, or functional group that binds to another chemical entity to form a larger complex
• receptor: a protein on a cell wall that binds with specific molecules so that they can be absorbed into the cell in order to control certain functions | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/09%3A_Cell_Communication/9.04%3A_Signaling_Molecules_and_Cellular_Receptors_-_Signaling_Molecules.txt |
Learning Objectives
• Explain how the binding of a ligand initiates signal transduction throughout a cell
The induction of a signaling pathway depends on the modification of a cellular component by an enzyme. There are numerous enzymatic modifications that can occur which are recognized in turn by the next component downstream.
One of the most common chemical modifications that occurs in signaling pathways is the addition of a phosphate group (PO4–3) to a molecule such as a protein in a process called phosphorylation. The phosphate can be added to a nucleotide such as GMP to form GDP or GTP. Phosphates are also often added to serine, threonine, and tyrosine residues of proteins where they replace the hydroxyl group of the amino acid. The transfer of the phosphate is catalyzed by an enzyme called a kinase. Various kinases are named for the substrate they phosphorylate. Phosphorylation of serine and threonine residues often activates enzymes. Phosphorylation of tyrosine residues can either affect the activity of an enzyme or create a binding site that interacts with downstream components in the signaling cascade. Phosphorylation may activate or inactivate enzymes; the reversal of phosphorylation, dephosphorylation by a phosphatase, will reverse the effect.
The activation of second messengers is also a common event after the induction of a signaling pathway. They are small molecules that propagate a signal after it has been initiated by the binding of the signaling molecule to the receptor. These molecules help to spread a signal through the cytoplasm by altering the behavior of certain cellular proteins.
Calcium ion is a widely-used second messenger. The free concentration of calcium ions (Ca2+) within a cell is very low because ion pumps in the plasma membrane continuously use adenosine-5′-triphosphate ( ATP ) to remove it. For signaling purposes, Ca2+ is stored in cytoplasmic vesicles, such as the endoplasmic reticulum, or accessed from outside the cell. When signaling occurs, ligand-gated calcium ion channels allow the higher levels of Ca2+ that are present outside the cell (or in intracellular storage compartments) to flow into the cytoplasm, which raises the concentration of cytoplasmic Ca2+. The response to the increase in Ca2+ varies, depending on the cell type involved. For example, in the β-cells of the pancreas, Ca2+ signaling leads to the release of insulin, whereas in muscle cells, an increase in Ca2+ leads to muscle contractions.
Another second messenger utilized in many different cell types is cyclic AMP (cAMP). Cyclic AMP is synthesized by the enzyme adenylyl cyclase from ATP. The main role of cAMP in cells is to bind to and activate an enzyme called cAMP-dependent kinase (A-kinase). A-kinase regulates many vital metabolic pathways. It phosphorylates serine and threonine residues of its target proteins, activating them in the process. A-kinase is found in many different types of cells; the target proteins in each kind of cell are different. Differences give rise to the variation of the responses to cAMP in different cells.
Present in small concentrations in the plasma membrane, inositol phospholipids are lipids that can also be converted into second messengers. Because these molecules are membrane components, they are located near membrane-bound receptors and can easily interact with them. Phosphatidylinositol (PI) is the main phospholipid that plays a role in cellular signaling. Enzymes known as kinases phosphorylate PI to form PI-phosphate (PIP) and PI-bisphosphate (PIP2).
Key Points
• Phosphorylation, the addition of a phosphate group to a molecule such as a protein, is one of the most common chemical modifications that occurs in signaling pathways.
• The activation of second messengers, small molecules that propagate a signal, is a common event after the induction of a signaling pathway.
• Calcium ion, cyclic AMP, and inositol phospholipids are examples of widely-used second messengers.
Key Terms
• second messenger: any substance used to transmit a signal within a cell, especially one which triggers a cascade of events by activating cellular components
• phosphorylation: the addition of a phosphate group to a compound; often catalyzed by enzymes
9.07: Response to the Cellular Signal - Termination of the Signal Cascade
Learning Objectives
• Describe the process by which the signal cascade in cell communication is terminated
Termination of the Signal Cascade
Ligand binding to the receptor allows for signal transduction through the cell. The chain of events that conveys the signal through the cell is called a signaling pathway or cascade. Signaling pathways are often very complex because of the interplay between different proteins. A major component of cell signaling cascades is the phosphorylation of molecules by enzymes known as kinases. Phosphorylation adds a phosphate group to serine, threonine, and tyrosine residues in a protein, changing their shapes, and activating or inactivating the protein.
The aberrant signaling often seen in tumor cells is proof that the termination of a signal at the appropriate time can be just as important as the initiation of a signal. One method of terminating or stopping a specific signal is to degrade or remove the ligand so that it can no longer access its receptor. One reason that hydrophobic hormones like estrogen and testosterone trigger long-lasting events is because they bind carrier proteins. These proteins allow the insoluble molecules to be soluble in blood, but they also protect the hormones from degradation by circulating enzymes.
Inside the cell, many different enzymes reverse the cellular modifications that result from signaling cascades. For example, phosphatases are enzymes that remove the phosphate group attached to proteins by kinases in a process called dephosphorylation. Cyclic AMP (cAMP) is degraded into AMP by phosphodiesterase, and the release of calcium stores is reversed by the Ca2+ pumps that are located in the external and internal membranes of the cell.
Key Points
• The chain of events that conveys the signal through the cell is called a signaling pathway or cascade.
• Phosphorylation, a major component of signal cascades, adds a phosphate group to proteins, thereby changing their shapes and activating or inactivating the protein.
• Degrading or removing the ligand so it can no longer access its receptor terminates the signal.
• Enzymes like phosphotases can remove phosphate groups on proteins during dephosphorylation and reverse the cellular modifications produced by signaling cascades.
Key Terms
• signaling cascade: the chain of events that conveys the signal through the cell
• phosphorylation: the addition of a phosphate group to a compound; often catalyzed by enzymes
• dephosphorylation: the removal of phosphate groups from a compound; often catalyzed by enzymes | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/09%3A_Cell_Communication/9.06%3A_Propagation_of_the_Cellular_Signal_-_Methods_of_Intracellular_Signaling.txt |
Learning Objectives
• Describe the regulation of gene expression
Gene Expression
For a cell to function properly, necessary proteins must be synthesized at the proper time. All cells control or regulate the synthesis of proteins from information encoded in their DNA. The process of turning on a gene to produce RNA and protein is called gene expression.
Whether in a simple unicellular organism or a complex multi-cellular organism, each cell controls when and how its genes are expressed. For this to occur, there must be a mechanism to control when a gene is expressed to make RNA and protein; how much of the protein is made; and when it is time to stop making that protein because it is no longer needed. The regulation of gene expression conserves energy and space. It would require a significant amount of energy for an organism to express every gene at all times, so it is more energy efficient to turn on the genes only when they are required. In addition, only expressing a subset of genes in each cell saves space because DNA must be unwound from its tightly-coiled structure to transcribe and translate the DNA. Cells would have to be enormous if every protein were expressed in every cell all the time. The control of gene expression is extremely complex. Malfunctions in this process are detrimental to the cell and can lead to the development of many diseases, including cancer.
Prokaryotic versus Eukaryotic Gene Expression
To understand how gene expression is regulated, we must first understand how a gene codes for a functional protein in a cell. The process occurs in both prokaryotic and eukaryotic cells, just in slightly different manners. Prokaryotic organisms are single-celled organisms that lack a cell nucleus; their DNA floats freely in the cell cytoplasm. To synthesize a protein, the processes of transcription and translation occur almost simultaneously. When the resulting protein is no longer needed, transcription stops. As a result, the primary method to control what type of protein and how much of each protein is expressed in a prokaryotic cell is the regulation of DNA transcription. All of the subsequent steps occur automatically. When more protein is required, more transcription occurs. Therefore, in prokaryotic cells, the control of gene expression is mostly at the transcriptional level.
Eukaryotic cells, in contrast, have intracellular organelles that add to their complexity. In eukaryotic cells, the DNA is contained inside the cell’s nucleus where it is transcribed into RNA. The newly-synthesized RNA is then transported out of the nucleus into the cytoplasm where ribosomes translate the RNA into protein. The processes of transcription and translation are physically separated by the nuclear membrane: transcription occurs only within the nucleus, and translation occurs only outside the nucleus in the cytoplasm. The regulation of gene expression can occur at all stages of the process. Regulation may occur when the DNA is uncoiled and loosened from nucleosomes to bind transcription factors (epigenetic level); when the RNA is transcribed (transcriptional level); when the RNA is processed and exported to the cytoplasm after it is transcribed (post-transcriptional level); when the RNA is translated into protein (translational level); or after the protein has been made (post-translational level).
Key Points
• Each cell controls when and how its genes are expressed.
• Malfunctions in the control of gene expression are detrimental to the cell and can lead to the development of many diseases, such as cancer.
• In prokaryotic cells, the control of gene expression is mostly at the transcriptional level.
• In eukaryotic cells, the control of gene expression is at the epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels.
Key Terms
• translation: a process occurring in the ribosome in which a strand of messenger RNA (mRNA) guides assembly of a sequence of amino acids to make a protein
• gene expression: the transcription and translation of a gene into messenger RNA and, thus, into a protein
• transcription: the synthesis of RNA under the direction of DNA | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/09%3A_Cell_Communication/9.08%3A_Response_to_the_Cellular_Signal_-_Cell_Signaling_and_Gene_Expression.txt |
Learning Objectives
• Explain how cellular metabolism can be altered
Increase in Cellular Metabolism
As the environments of most organisms are constantly changing, the reactions of metabolism must be finely regulated to maintain a constant set of conditions within cells. Metabolic regulation also allows organisms to respond to signals and interact actively with their environments. Two closely-linked concepts are important for understanding how metabolic pathways are controlled. Firstly, the regulation of an enzyme in a pathway is how its activity is increased and decreased in response to signals. Secondly, the controlexerted by this enzyme is the effect that these changes in its activity have on the overall rate of the pathway. For example, an enzyme may show large changes in activity (i.e. it is highly regulated), but if these changes have little effect on the rate of a metabolic pathway, then this enzyme is not involved in the control of the pathway.
The result of one such signaling pathway affects muscle cells and is a good example of an increase in cellular metabolism. The activation of β-adrenergic receptors in muscle cells by adrenaline leads to an increase in cyclic adenosine monophosphate (also known as cyclic AMP or cAMP) inside the cell. Also known as epinephrine, adrenaline is a hormone (produced by the adrenal gland attached to the kidney) that prepares the body for short-term emergencies. Cyclic AMP activates PKA (protein kinase A), which in turn phosphorylates two enzymes. The first enzyme promotes the degradation of glycogen by activating intermediate glycogen phosphorylase kinase (GPK) that in turn activates glycogen phosphorylase (GP), which catabolizes glycogen into glucose. (Recall that your body converts excess glucose to glycogen for short-term storage. When energy is needed, glycogen is quickly reconverted to glucose. ) Phosphorylation of the second enzyme, glycogen synthase (GS), inhibits its ability to form glycogen from glucose. In this manner, a muscle cell obtains a ready pool of glucose by activating its formation via glycogen degradation and by inhibiting the use of glucose to form glycogen, thus preventing a futile cycle of glycogen degradation and synthesis. The glucose is then available for use by the muscle cell in response to a sudden surge of adrenaline—the “fight or flight” reflex.
Key Points
• The activation of β-adrenergic receptors in muscle cells by adrenaline leads to an increase in cyclic AMP.
• Cyclic AMP activates PKA (protein kinase A), which phosphorylates two enzymes.
• Phophorylation of the first enzyme promotes the degradation of glycogen by activating intermediate GPK that in turn activates GP, which catabolizes glycogen into glucose.
• Phosphorylation of the second enzyme, glycogen synthase (GS), inhibits its ability to form glycogen from glucose.
• The inhibition of glucose to form glycogen prevents a futile cycle of glycogen degradation and synthesis, so glucose is then available for use by the muscle cell.
Key Terms
• cyclic adenosine monophosphate: cAMP, a second messenger derived from ATP that is involved in the activation of protein kinases and regulates the effects of adrenaline
• epinephrine: (adrenaline) an amino acid-derived hormone secreted by the adrenal gland in response to stress
• protein kinase A: a family of enzymes whose activity is dependent on cellular levels of cyclic AMP (cAMP) | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/09%3A_Cell_Communication/9.09%3A_Response_to_the_Cellular_Signal_-_Cell_Signaling_and_Cellular_Metabolism.txt |
Learning Objectives
• Explain how cell growth is affected by growth factors.
Cell Growth
Cell signaling pathways play a major role in cell division. Cells do not normally divide unless they are stimulated by signals from other cells. The ligands that promote cell growth are called growth factors. Most growth factors bind to cell-surface receptors that are linked to tyrosine kinases. These cell-surface receptors are called receptor tyrosine kinases (RTKs). Activation of RTKs initiates a signaling pathway that includes a G-protein called RAS, which activates the MAP kinase pathway described earlier. The enzyme MAP kinase then stimulates the expression of proteins that interact with other cellular components to initiate cell division. In addition, uncontrolled cell growth leads to cancer; mutations in the genes encoding protein components of signaling pathways are often found in tumor cells.
Cancer Biologists & Uncontrolled Cell Growth
Cancer biologists study the molecular origins of cancer with the goal of developing new prevention methods and treatment strategies that will inhibit the growth of tumors without harming the normal cells of the body. Signaling pathways control cell growth. These pathways are controlled by signaling proteins, which are, in turn, expressed by genes. Mutations in these genes can result in malfunctioning signaling proteins. This prevents the cell from regulating its cell cycle, triggering unrestricted cell division and cancer. The genes that regulate the signaling proteins are one type of oncogene: a gene that has the potential to cause cancer. The gene encoding RAS is an oncogene that was originally discovered when mutations in the RAS protein were linked to cancer. Further studies have indicated that 30 percent of cancer cells have a mutation in the RAS gene that leads to uncontrolled growth. If left unchecked, uncontrolled cell division can lead tumor formation and metastasis, the growth of cancer cells in new locations in the body.
Cancer biologists have been able to identify many other oncogenes that contribute to the development of cancer. For example, HER2 is a cell-surface receptor that is present in excessive amounts in 20 percent of human breast cancers. Cancer biologists realized that gene duplication led to HER2 overexpression in 25 percent of breast cancer patients and developed a drug called Herceptin (trastuzumab), a monoclonal antibody that targets HER2 for removal by the immune system. Herceptin therapy helps to control signaling through HER2. Its use, in combination with chemotherapy, has helped to increase the overall survival rate of patients with metastatic breast cancer.
Key Points
• Normally, cells do not divide unless they are stimulated by signals from other cells.
• Most growth factors, which promote cell growth, bind to cell-surface receptors that are linked to tyrosine kinases.
• MAP kinase stimulates the expression of proteins that interact with other cellular components to initiate cell division.
• Uncontrolled cell growth leads to cancer.
Key Terms
• receptor: a protein on a cell wall that binds with specific molecules so that they can be absorbed into the cell in order to control certain functions
• growth factor: a naturally-occurring substance capable of stimulating cellular growth, proliferation, and cellular differentiation
• oncogene: any gene that contributes to the conversion of a normal cell into a cancerous cell when mutated or expressed at high levels | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/09%3A_Cell_Communication/9.10%3A_Response_to_the_Cellular_Signal_-_Cell_Signaling_and_Cell_Growth.txt |
Learning Objectives
• Describe how apoptosis is initiated
Apoptosis
When a cell is damaged, superfluous, or potentially dangerous to an organism, a cell can initiate a mechanism to trigger programmed cell death, or apoptosis. Apoptosis allows a cell to die in a controlled manner that prevents the release of potentially damaging molecules from inside the cell.
Internal Signaling
There are many internal checkpoints that monitor a cell’s health; if abnormalities are observed, a cell can spontaneously initiate the process of apoptosis. However, in some cases such as a viral infection or uncontrolled cell division due to cancer, the cell’s normal checks and balances fail.
External Signaling
External signaling can also initiate apoptosis. For example, most normal animal cells have receptors that interact with the extracellular matrix, a network of glycoproteins that provides structural support for cells in an organism. The binding of cellular receptors to the extracellular matrix initiates a signaling cascade within the cell. However, if the cell moves away from the extracellular matrix, the signaling ceases, and the cell undergoes apoptosis. This system keeps cells from traveling through the body and proliferating out of control, as happens with tumor cells that metastasize.
Another example of external signaling that leads to apoptosis occurs in T-cell development. T-cells are immune cells that bind to foreign macromolecules and particles, targeting them for destruction by the immune system. Normally, T-cells do not target “self” proteins (those of their own organism), a process that can lead to autoimmune diseases. In order to develop the ability to discriminate between self and non-self, immature T-cells undergo screening to determine whether they bind to so-called self proteins. If the T-cell receptor binds to self proteins, the cell initiates apoptosis to remove the potentially dangerous cell.
Apoptosis and Embryos
Apoptosis is also essential for normal embryological development. In vertebrates, for example, early stages of development include the formation of web-like tissue between individual fingers and toes. During the course of normal development, these unnecessary cells must be eliminated, enabling fully separated fingers and toes to form. A cell signaling mechanism triggers apoptosis, which destroys the cells between the developing digits.
Key Points
• Apoptosis allows a cell to die in a controlled manner by preventing the release of damaging molecules from inside the cell.
• Internal checkpoints to monitor a cell’s health exist; if abnormalities are observed, a cell can also spontaneously initiate the process of apoptosis.
• In some cases, such as a viral infection or cancer, the cell’s normal checks and balances fail.
• External signaling can also initiate apoptosis.
• Apoptosis is also essential for normal embryological development; unnecessary cells that appear during the early stages of development will eventually be eliminated through cell signaling.
Key Terms
• apoptosis: a process of programmed cell death
• glycoprotein: a protein with covalently-bonded carbohydrates
9.12: Signaling in Single-Celled Organisms - Signaling in Yeast
Learning Objectives
• Describe how cell signaling occurs in single-celled organisms such as yeast
Signaling in Yeast
Yeasts are single-celled eukaryotes; therefore, they have a nucleus and organelles characteristic of more complex life forms. Comparisons of the genomes of yeasts, nematode worms, fruit flies, and humans illustrate the evolution of increasingly-complex signaling systems that allow for the efficient inner workings that keep humans and other complex life forms functioning correctly.
The components and processes found in yeast signals are similar to those of cell-surface receptor signals in multicellular organisms. Budding yeasts are able to participate in a process that is similar to sexual reproduction that entails two haploid cells combining to form a diploid cell. In order to find another haploid yeast cell that is prepared to mate, budding yeasts secrete a signaling molecule called mating factor. When mating factor binds to cell-surface receptors in other yeast cells that are nearby, they stop their normal growth cycles and initiate a cell signaling cascade that includes protein kinases and GTP-binding proteins that are similar to G-proteins.
Cellular Communication in Yeasts
Kinases are a major component of cellular communication. Studies of these enzymes illustrate the evolutionary connectivity of different species. Yeasts have 130 types of kinases. More complex organisms such as nematode worms and fruit flies have 454 and 239 kinases, respectively. Of the 130 kinase types in yeast, 97 belong to the 55 subfamilies of kinases that are found in other eukaryotic organisms. The only obvious deficiency seen in yeasts is the complete absence of tyrosine kinases. It is hypothesized that phosphorylation of tyrosine residues is needed to control the more sophisticated functions of development, differentiation, and cellular communication used in multicellular organisms.
Because yeasts contain many of the same classes of signaling proteins as humans, these organisms are ideal for studying signaling cascades. Yeasts multiply quickly and are much simpler organisms than humans or other multicellular animals. Therefore, the signaling cascades are also simpler and easier to study, although they contain similar counterparts to human signaling
Key Points
• Budding yeasts participate in a process that is similar to sexual reproduction that entails two haploid cells combining to form a diploid cell.
• Budding yeasts secrete a signaling molecule called mating factor when trying to find another haploid yeast cell that is ready to mate.
• In yeast, a cell signaling cascade is initiated when a mating factor binds to cell-surface receptors in other yeast cells.
• A cell signaling cascade includes protein kinases and GTP-binding proteins that are similar to G-proteins.
• Yeasts have 130 types of kinases, but they do not contain tyrosine kinases, which are utilized by multicellular organisms to control complex forms of development and communication.
Key Terms
• kinase: any of a group of enzymes that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific target molecules (substrates); the process is termed phosphorylation
• GTP-binding protein: a protein which binds GTP and catalyzes its conversion to GDP
• G protein: any of a class of proteins, found in cell membranes, that pass signals between hormone receptors and effector enzymes
9.13: Signaling in Single-Celled Organisms - Signaling in Bacteria
Learning Objectives
• Describe how cell signaling occurs in single-celled organisms such as bacteria
Signaling in Bacteria
Signaling in bacteria, known as quorum sensing, enables bacteria to monitor extracellular conditions, ensure sufficient amounts of nutrients are present, and avoid hazardous situations. There are circumstances, however, when bacteria communicate with each other.
The first evidence of bacterial communication was observed in a bacterium that has a symbiotic relationship with Hawaiian bobtail squid. When the population density of the bacteria reached a certain level, specific gene expression was initiated: the bacteria produced bioluminescent proteins that emitted light. Because the number of cells present in the environment (the cell density) is the determining factor for signaling, bacterial signaling was named quorum sensing. Interestingly, in politics and business, a quorum is the minimum number of members required to be present to vote on an issue.
Quorum sensing uses autoinducers as signaling molecules. Autoinducers are signaling molecules secreted by bacteria to communicate with other bacteria of the same kind. The secreted autoinducers can be small, hydrophobic molecules, such as acyl-homoserine lactone (AHL), or larger peptide-based molecules. Each type of molecule has a different mode of action. When AHL enters target bacteria, it binds to transcription factors, which then switch gene expression on or off. The peptide autoinducers stimulate more complicated signaling pathways that include bacterial kinases. The changes in bacteria following exposure to autoinducers can be quite extensive. The pathogenic bacterium Pseudomonas aeruginosa has 616 different genes that respond to autoinducers.
Some species of bacteria that use quorum sensing form biofilms, which are complex colonies of bacteria (often containing several species) that exchange chemical signals to coordinate the release of toxins that attack the host. Bacterial biofilms can sometimes be found on medical equipment. When biofilms invade implants, such as hip or knee replacements or heart pacemakers, they can cause life-threatening infections.
Key Points
• Gene expression in bacteria is initiated when the population density of the bacteria reaches a certain level.
• Bacterial signaling is called quorum sensing because cell density is the determining factor for signaling.
• Quorum sensing uses autoinducers, which are secreted by bacteria to communicate with other bacteria of the same kind, as signaling molecules.
• Autoinducers may be small, hydrophobic molecules, or they can be larger peptide-based molecules; regardless, each type of molecule has a different mode of action.
• Some bacteria form biofilms, which are complex colonies of bacteria that exchange chemical signals to coordinate the release of toxins that attack the host.
Key Terms
• quorum sensing: a method of communication between bacterial cells by the release and sensing of small diffusible signal molecules
• autoinducer: any of several compounds, synthesized by bacteria, that have signalling functions in quorum sensing
• biofilm: a thin film of mucus created by and containing a colony of bacteria and other microorganisms | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/09%3A_Cell_Communication/9.11%3A_Response_to_the_Cellular_Signal_-_Cell_Signaling_and_Cell_Death.txt |
Learning Objectives
• Explain the role of the cell cycle in carrying out the cell’s essential functions
Introduction: Cell Division and Reproduction
A human, as well as every sexually-reproducing organism, begins life as a fertilized egg or zygote. Trillions of cell divisions subsequently occur in a controlled manner to produce a complex, multicellular human. In other words, that original single cell is the ancestor of every other cell in the body. Once a being is fully grown, cell reproduction is still necessary to repair or regenerate tissues. For example, new blood and skin cells are constantly being produced. All multicellular organisms use cell division for growth and the maintenance and repair of cells and tissues. Cell division is tightly regulated because the occasional failure of regulation can have life-threatening consequences. Single-celled organisms use cell division as their method of reproduction.
While there are a few cells in the body that do not undergo cell division, most somatic cells divide regularly. A somatic cell is a general term for a body cell: all human cells, except for the cells that produce eggs and sperm (which are referred to as germ cells), are somatic cells. Somatic cells contain two copies of each of their chromosomes (one copy received from each parent). Cells in the body replace themselves over the lifetime of a person. For example, the cells lining the gastrointestinal tract must be frequently replaced when constantly “worn off” by the movement of food through the gut. But what triggers a cell to divide and how does it prepare for and complete cell division?
The cell cycle is an ordered series of events involving cell growth and cell division that produces two new daughter cells. Cells on the path to cell division proceed through a series of precisely timed and carefully regulated stages of growth, DNA replication, and division that produces two identical (clone) cells. The cell cycle has two major phases: interphase and the mitotic phase. During interphase, the cell grows and DNA is replicated. During the mitotic phase, the replicated DNA and cytoplasmic contents are separated and the cell divides.
Key Points
• All multicellular organisms use cell division for growth and the maintenance and repair of cells and tissues.
• Single-celled organisms use cell division as their method of reproduction.
• Somatic cells divide regularly; all human cells (except for the cells that produce eggs and sperm) are somatic cells.
• Somatic cells contain two copies of each of their chromosomes (one copy from each parent).
• The cell cycle has two major phases: interphase and the mitotic phase.
• During interphase, the cell grows and DNA is replicated; during the mitotic phase, the replicated DNA and cytoplasmic contents are separated and the cell divides.
Key Terms
• somatic cell: any normal body cell of an organism that is not involved in reproduction; a cell that is not on the germline
• interphase: the stage in the life cycle of a cell where the cell grows and DNA is replicated
• mitotic phase: replicated DNA and the cytoplasmic material are divided into two identical cells | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/10%3A_Cell_Reproduction/10.01%3A_Cell_Division/10.1A%3A_The_Role_of_the_Cell_Cycle.txt |
Learning Objectives
• Explain the importance of a genome to an organism
Genomic DNA
Before discussing the steps a cell must undertake to replicate, a deeper understanding of the structure and function of a cell’s genetic information is necessary. A cell’s DNA, packaged as a double-stranded DNA molecule, is called its genome. In prokaryotes, the genome is composed of a single, double-stranded DNA molecule in the form of a loop or circle. The region in the cell containing this genetic material is called a nucleoid. Some prokaryotes also have smaller loops of DNA called plasmids that are not essential for normal growth. Bacteria can exchange these plasmids with other bacteria, sometimes receiving beneficial new genes that the recipient can add to their chromosomal DNA. Antibiotic resistance is one trait that often spreads through a bacterial colony through plasmid exchange.
In eukaryotes, the genome consists of several double-stranded linear DNA molecules packaged into chromosomes. Each species of eukaryotes has a characteristic number of chromosomes in the nuclei of its cells. Human body cells have 46 chromosomes, while human gametes (sperm or eggs) have 23 chromosomes each. A typical body cell, or somatic cell, contains two matched sets of chromosomes, a configuration known as diploid. The letter n is used to represent a single set of chromosomes; therefore, a diploid organism is designated 2n. Human cells that contain one set of chromosomes are called gametes, or sex cells; these are eggs and sperm, and are designated 1n, or haploid.
Matched pairs of chromosomes in a diploid organism are called homologous (“same knowledge”) chromosomes. Homologous chromosomes are the same length and have specific nucleotide segments called genes in exactly the same location, or locus. Genes, the functional units of chromosomes, determine specific characteristics, or traits, by coding for specific proteins. For example, hair color is a trait that can be blonde, brown, or black.
Each copy of a homologous pair of chromosomes originates from a different parent; therefore, the genes themselves are not identical. The variation of individuals within a species is due to the specific combination of the genes inherited from both parents. Even a slightly altered sequence of nucleotides within a gene can result in an alternative trait. For example, there are three possible gene sequences on the human chromosome that code for blood type: sequence A, sequence B, and sequence O. Because all diploid human cells have two copies of the chromosome that determines blood type, the blood type (the trait) is determined by which two versions of the marker gene are inherited. It is possible to have two copies of the same gene sequence on both homologous chromosomes, with one on each (for example, AA, BB, or OO), or two different sequences, such as AB, AO, or BO.
Minor variations of traits, such as blood type, eye color, and handedness, contribute to the natural variation found within a species. However, if the entire DNA sequence from any pair of human homologous chromosomes is compared, the difference is less than one percent. The sex chromosomes, X and Y, are the single exception to the rule of homologous chromosome uniformity. Other than a small amount of homology that is necessary to accurately produce gametes, the genes found on the X and Y chromosomes are different.
Key Points
• A cell ‘s DNA, packaged as a double-stranded DNA molecule, is called its genome.
• In prokaryotes, the genome is composed of a single, double-stranded DNA molecule in the form of a loop or circle; the region in the cell containing this genetic material is called a nucleoid.
• In eukaryotes, the genome consists of several double-stranded linear DNA molecules; each species of eukaryotes has a characteristic number of chromosomes in the nuclei of its cells.
• Matched pairs of chromosomes in a diploid organism are called homologous chromosomes, which are the same length and have specific nucleotide segments called genes in exactly the same location, or locus.
• Each copy of a homologous pair of chromosomes originates from a different parent, so the genes themselves are not identical.
• The difference between the DNA sequences in pairs of homologous chromosomes is less than one percent; the sex chromosomes, X and Y, are the single exception to this rule since their genes are different.
Key Terms
• genome: the cell’s complete genetic information packaged as a double-stranded DNA molecule
• nucleoid: the irregularly-shaped region within a prokaryote cell where the genetic material is localized
• gene: a unit of heredity; the functional units of chromosomes that determine specific characteristics by coding for specific proteins
• chromosome: a structure in the cell nucleus that contains DNA, histone protein, and other structural proteins
• locus: a fixed position on a chromosome that may be occupied by one or more genes | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/10%3A_Cell_Reproduction/10.01%3A_Cell_Division/10.1B%3A_Genomic_DNA_and_Chromosomes.txt |
Learning Objectives
• Describe the levels of chromsomal structure and compaction
Eukaryotic Chromosomal Structure and Compaction
If the DNA from all 46 chromosomes in a human cell nucleus was laid out end to end, it would measure approximately two meters. However, the diameter would be only 2 nm. Considering that the size of a typical human cell is about 10 µm (100,000 cells lined up to equal one meter), DNA must be tightly packaged to fit in the cell’s nucleus. At the same time, it must also be readily accessible for the genes to be expressed. During some stages of the cell cycle, the long strands of DNA are condensed into compact chromosomes. There are a number of ways that chromosomes are compacted to fit in the cell’s nucleus and be accessible for gene expression.
In the first level of compaction, short stretches of the DNA double helix wrap around a core of eight histone proteins at regular intervals along the entire length of the chromosome. The DNA-histone complex is called chromatin. The beadlike, histone DNA complex is called a nucleosome. DNA connecting the nucleosomes is called linker DNA. A DNA molecule in this form is about seven times shorter than the double helix without the histones. The beads are about 10 nm in diameter, in contrast with the 2-nm diameter of a DNA double helix. The next level of compaction occurs as the nucleosomes and the linker DNA between them are coiled into a 30-nm chromatin fiber. This coiling further shortens the chromosome so that it is now about 50 times shorter than the extended form. In the third level of packing, a variety of fibrous proteins is used to pack the chromatin. These fibrous proteins also ensure that each chromosome in a non-dividing cell occupies a particular area of the nucleus that does not overlap with that of any other chromosome.
DNA replicates in the S phase of interphase. After replication, the chromosomes are composed of two linked sister chromatids. When fully compact, the pairs of identically-packed chromosomes are bound to each other by cohesin proteins. The connection between the sister chromatids is closest in a region called the centromere. The conjoined sister chromatids, with a diameter of about 1 µm, are visible under a light microscope. The centromeric region is highly condensed and will appear as a constricted area.
Key Points
• During some stages of the cell cycle, the long strands of DNA are condensed into compact chromosomes to fit in the cell’s nucleus.
• In the first level of compaction, short stretches of the DNA double helix wrap around a core of eight histone proteins at regular intervals along the entire length of the chromosome.
• The DNA surrouding the histone core is called a nucleosome; the DNA-histone complex is called chromatin.
• The second level of compaction occurs as the nucleosomes and the linker DNA between them are coiled into a 30-nm chromatin fiber, which shortens the chromosome so it’s about 50 times shorter than the extended form.
• After replication, the chromosomes are composed of two linked sister chromatids; when fully compact, the pairs of identically-packed chromosomes are bound to each other by cohesin proteins.
• The connection between the sister chromatids is closest in a region called the centromere; this region is highly condensed.
Key Terms
• nucleosome: any of the subunits that repeat in chromatin; a coil of DNA surrounding a histone core
• histone: any of various simple water-soluble proteins that are rich in the basic amino acids lysine and arginine and are complexed with DNA in the nucleosomes of eukaryotic chromatin
• chromatin: a complex of DNA, RNA, and proteins within the cell nucleus out of which chromosomes condense during cell division | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/10%3A_Cell_Reproduction/10.01%3A_Cell_Division/10.1C%3A_Eukaryotic_Chromosomal_Structure_and_Compaction.txt |
Learning Objectives
• Describe the events that occur during Interphase
Interphase
During interphase, the cell undergoes normal growth processes while also preparing for cell division. In order for a cell to move from interphase into the mitotic phase, many internal and external conditions must be met. The three stages of interphase are called G1, S, and G2 .
G1 Phase (First Gap)
The first stage of interphase is called the G1 phase (first gap) because, from a microscopic aspect, little change is visible. However, during the G1 stage, the cell is quite active at the biochemical level. The cell grows and accumulates the building blocks of chromosomal DNA and the associated proteins as well as sufficient energy reserves to complete the task of replicating each chromosome in the nucleus.
S Phase (Synthesis of DNA)
The synthesis phase of interphase takes the longest because of the complexity of the genetic material being duplicated. Throughout interphase, nuclear DNA remains in a semi-condensed chromatin configuration. In the S phase, DNA replication results in the formation of identical pairs of DNA molecules, sister chromatids, that are firmly attached to the centromeric region. The centrosome is duplicated during the S phase. The two centrosomes will give rise to the mitotic spindle, the apparatus that orchestrates the movement of chromosomes during mitosis. At the center of each animal cell, the centrosomes of animal cells are associated with a pair of rod-like objects, the centrioles, which are at right angles to each other. Centrioles help organize cell division. Centrioles are not present in the centrosomes of other eukaryotic species, such as plants and most fungi.
G2 Phase (Second Gap)
In the G2 phase, the cell replenishes its energy stores and synthesizes proteins necessary for chromosome manipulation. Some cell organelles are duplicated, and the cytoskeleton is dismantled to provide resources for the mitotic phase. There may be additional cell growth during G2. The final preparations for the mitotic phase must be completed before the cell is able to enter the first stage of mitosis.
Key Points
• There are three stages of interphase: G1 (first gap), S (synthesis of new DNA ), and G2 (second gap).
• Cells spend most of their lives in interphase, specifically in the S phase where genetic material must be copied.
• The cell grows and carries out biochemical functions, such as protein synthesis, in the G1 phase.
• During the S phase, DNA is duplicated into two sister chromatids, and centrosomes, which give rise to the mitotic spindle, are also replicated.
• In the G2 phase, energy is replenished, new proteins are synthesized, the cytoskeleton is dismantled, and additional growth occurs.
Key Terms
• interphase: the stage in the life cycle of a cell where the cell grows and DNA is replicated
• sister chromatid: either of the two identical strands of a chromosome (DNA material) that separate during mitosis
• mitotic spindle: the apparatus that orchestrates the movement of chromosomes during mitosis
10.2B: The Mitotic Phase and the G0 Phase
Learning Objectives
• Describe the events that occur at the different stages of mitosis
The Mitotic Phase
The mitotic phase is a multistep process during which the duplicated chromosomes are aligned, separated, and move into two new, identical daughter cells. The first portion of the mitotic phase is called karyokinesis or nuclear division. The second portion of the mitotic phase, called cytokinesis, is the physical separation of the cytoplasmic components into the two daughter cells.
Karyokinesis (Mitosis)
Karyokinesis, also known as mitosis, is divided into a series of phases (prophase, prometaphase, metaphase, anaphase, and telophase) that result in the division of the cell nucleus.
During prophase, the “first phase,” the nuclear envelope starts to dissociate into small vesicles. The membranous organelles (such as the Golgi apparatus and endoplasmic reticulum) fragment and disperse toward the periphery of the cell. The nucleolus disappears and the centrosomes begin to move to opposite poles of the cell. Microtubules that will eventually form the mitotic spindle extend between the centrosomes, pushing them farther apart as the microtubule fibers lengthen. The sister chromatids begin to coil more tightly with the aid of condensin proteins and become visible under a light microscope.
During prometaphase, the “first change phase,” many processes that began in prophase continue to advance. The remnants of the nuclear envelope fragment. The mitotic spindle continues to develop as more microtubules assemble and stretch across the length of the former nuclear area. Chromosomes become more condensed and discrete. Each sister chromatid develops a protein structure called a kinetochore in the centromeric region. The proteins of the kinetochore attract and bind mitotic spindle microtubules.
During metaphase, the “change phase,” all the chromosomes are aligned on a plane called the metaphase plate, or the equatorial plane, midway between the two poles of the cell. The sister chromatids are still tightly attached to each other by cohesin proteins. At this time, the chromosomes are maximally condensed.
During anaphase, the “upward phase,” the cohesin proteins degrade, and the sister chromatids separate at the centromere. Each chromatid, now called a chromosome, is pulled rapidly toward the centrosome to which its microtubule is attached. The cell becomes visibly elongated (oval shaped) as the polar microtubules slide against each other at the metaphase plate where they overlap.
During telophase, the “distance phase,” the chromosomes reach the opposite poles and begin to decondense (unravel), relaxing into a chromatin configuration. The mitotic spindles are depolymerized into tubulin monomers that will be used to assemble cytoskeletal components for each daughter cell. Nuclear envelopes form around the chromosomes and nucleosomes appear within the nuclear area.
Cytokinesis
Cytokinesis, or “cell motion,” is the second main stage of the mitotic phase during which cell division is completed via the physical separation of the cytoplasmic components into two daughter cells. Division is not complete until the cell components have been apportioned and completely separated into the two daughter cells. Although the stages of mitosis are similar for most eukaryotes, the process of cytokinesis is quite different for eukaryotes that have cell walls, such as plant cells.
In cells such as animal cells, which lack cell walls, cytokinesis follows the onset of anaphase. A contractile ring composed of actin filaments forms just inside the plasma membrane at the former metaphase plate. The actin filaments pull the equator of the cell inward, forming a fissure. This fissure or “crack” is called the cleavage furrow. The furrow deepens as the actin ring contracts; eventually the membrane is cleaved in two.
In plant cells, a new cell wall must form between the daughter cells. During interphase, the Golgi apparatus accumulates enzymes, structural proteins, and glucose molecules prior to breaking into vesicles and dispersing throughout the dividing cell. During telophase, these Golgi vesicles are transported on microtubules to form a phragmoplast (a vesicular structure) at the metaphase plate. There, the vesicles fuse and coalesce from the center toward the cell walls; this structure is called a cell plate. As more vesicles fuse, the cell plate enlarges until it merges with the cell walls at the periphery of the cell. Enzymes use the glucose that has accumulated between the membrane layers to build a new cell wall. The Golgi membranes become parts of the plasma membrane on either side of the new cell wall.
G0 Phase
Not all cells adhere to the classic cell cycle pattern in which a newly-formed daughter cell immediately enters the preparatory phases of interphase, closely followed by the mitotic phase. Cells in G0 phase are not actively preparing to divide. The cell is in a quiescent (inactive) stage that occurs when cells exit the cell cycle. Some cells enter G0 temporarily until an external signal triggers the onset of G1. Other cells that never or rarely divide, such as mature cardiac muscle and nerve cells, remain in G0 permanently.
Key Points
• During prophase, the nucleus disappears, spindle fibers form, and DNA condenses into chromosomes ( sister chromatids ).
• During metaphase, the sister chromatids align along the equator of the cell by attaching their centromeres to the spindle fibers.
• During anaphase, sister chromatids are separated at the centromere and are pulled towards opposite poles of the cell by the mitotic spindle.
• During telophase, chromosomes arrive at opposite poles and unwind into thin strands of DNA, the spindle fibers disappear, and the nuclear membrane reappears.
• Cytokinesis is the actual splitting of the cell membrane; animal cells pinch apart, while plant cells form a cell plate that becomes the new cell wall.
• Cells enter the G0 (inactive) phase after they exit the cell cycle when they are not actively preparing to divide; some cells remain in G0 phase permanently.
Key Terms
• karyokinesis: (mitosis) the first portion of mitotic phase in which division of the cell nucleus takes place
• centrosome: an organelle near the nucleus in the cytoplasm of most organisms that controls the organization of its microtubules and gives rise to the mitotic spindle
• cytokinesis: the second portion of the mitotic phase in which the cytoplasm of a cell divides following the division of the nucleus | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/10%3A_Cell_Reproduction/10.02%3A_The_Cell_Cycle/10.2A%3A_Interphase.txt |
Learning Objectives
• Describe external events that can affect cell cycle regulation
Regulation of the Cell Cycle by External Events
Unlike the life of organisms, which is a straight progression from birth to death, the life of a cell takes place in a cyclical pattern. Each cell is produced as part of its parent cell. When a daughter cell divides, it turns into two new cells, which would lead to the assumption that each cell is capable of being immortal as long as its descendants can continue to divide. However, all cells in the body only live as long as the organism lives. Some cells do live longer than others, but eventually all cells die when their vital functions cease. Most cells in the body exist in the state of interphase, the non-dividing stage of the cell life cycle. When this stage ends, cells move into the dividing part of their lives called mitosis.
Both the initiation and inhibition of cell division are triggered by events external to the cell when it is about to begin the replication process. An event may be as simple as the death of a nearby cell or as sweeping as the release of growth-promoting hormones, such as human growth hormone (HGH). A lack of HGH can inhibit cell division, resulting in dwarfism, whereas too much HGH can result in gigantism. Crowding of cells can also inhibit cell division. Another factor that can initiate cell division is the size of the cell; as a cell grows, it becomes inefficient due to its decreasing surface-to-volume ratio. The solution to this problem is to divide.
Whatever the source of the message, the cell receives the signal, and a series of events within the cell allows it to proceed into interphase. Moving forward from this initiation point, every parameter required during each cell cycle phase must be met or the cycle cannot progress.
Key Points
• The death of nearby cells and the presence or absence of certain hormones can impact the cell cycle.
• The release of growth-promoting hormones, such as HGH, can initiate cell division, and a lack of these hormones can inhibit cell division.
• Cell growth initiates cell division because cells must divide as the surface-to-volume ratio decreases; cell crowding inhibits cell division.
• Key conditions must be met before the cell can move into interphase.
Key Terms
• gigantism: a condition caused by an over-production of growth hormone, resulting in excessive bone growth
• growth hormone: any polypeptide hormone secreted by the pituitary gland that promotes growth and regulates the metabolism of carbohydrates, proteins, and lipids
• dwarfism: a condition caused by a lack of growth hormone, resulting in short stature and limbs that are disproportionately small in relation to the body
10.3B: Regulation of the Cell Cycle at Internal Checkpoints
Learning Objectives
• Explain the effects of internal checkpoints on the regulation of the cell cycle
Regulation at Internal Checkpoints
It is essential that the daughter cells are exact duplicates of the parent cell. Mistakes in the duplication or distribution of the chromosomes lead to mutations that may be passed forward to every new cell produced from an abnormal cell. To prevent a compromised cell from continuing to divide, internal control mechanisms operate at three main cell cycle checkpoints. A checkpoint is one of several points in the eukaryotic cell cycle at which the progression of a cell to the next stage in the cycle can be halted until conditions are favorable (e.g. the DNA is repaired). These checkpoints occur near the end of G1, at the G2/M transition, and during metaphase.
The G1 Checkpoint
The G1 checkpoint determines whether all conditions are favorable for cell division to proceed. The G1 checkpoint, also called the restriction point (in yeast), is a point at which the cell irreversibly commits to the cell division process. External influences, such as growth factors, play a large role in carrying the cell past the G1 checkpoint. The cell will only pass the checkpoint if it is an appropriate size and has adequate energy reserves. At this point, the cell also checks for DNA damage. A cell that does not meet all the requirements will not progress to the S phase. The cell can halt the cycle and attempt to remedy the problematic condition, or the cell can advance into G0 (inactive) phase and await further signals when conditions improve.
If a cell meets the requirements for the G1 checkpoint, the cell will enter S phase and begin DNA replication. This transition, as with all of the major checkpoint transitions in the cell cycle, is signaled by cyclins and cyclin dependent kinases (CDKs). Cyclins are cell-signaling molecules that regulate the cell cycle.
The G2 Checkpoint
The G2 checkpoint bars entry into the mitotic phase if certain conditions are not met. As with the G1 checkpoint, cell size and protein reserves are assessed. However, the most important role of the G2 checkpoint is to ensure that all of the chromosomes have been accurately replicated without mistakes or damage. If the checkpoint mechanisms detect problems with the DNA, the cell cycle is halted and the cell attempts to either complete DNA replication or repair the damaged DNA. If the DNA has been correctly replicated, cyclin dependent kinases (CDKs) signal the beginning of mitotic cell division.
The M Checkpoint
The M checkpoint occurs near the end of the metaphase stage of mitosis. The M checkpoint is also known as the spindle checkpoint because it determines whether all the sister chromatids are correctly attached to the spindle microtubules. Because the separation of the sister chromatids during anaphase is an irreversible step, the cycle will not proceed until the kinetochores of each pair of sister chromatids are firmly anchored to at least two spindle fibers arising from opposite poles of the cell.
Key Points
• A checkpoint is one of several points in the eukaryotic cell cycle at which the progression of a cell to the next stage in the cycle can be halted until conditions are favorable.
• Damage to DNA and other external factors are evaluated at the G1 checkpoint; if conditions are inadequate, the cell will not be allowed to continue to the S phase of interphase.
• The G2 checkpoint ensures all of the chromosomes have been replicated and that the replicated DNA is not damaged before cell enters mitosis.
• The M checkpoint determines whether all the sister chromatids are correctly attached to the spindle microtubules before the cell enters the irreversible anaphase stage.
Key Terms
• restriction point: (G1 checkpoint) a point in the animal cell cycle at which the cell becomes “committed” to the cell cycle, which is determined by external factors and signals
• spindle checkpoint: (M checkpoint) prevents separation of the duplicated chromosomes until each chromosome is properly attached to the spindle apparatus
• cyclin: any of a group of proteins that regulates the cell cycle by forming a complex with kinases
• G2 checkpoint: ensures all of the chromosomes have been replicated and that the replicated DNA is not damaged | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/10%3A_Cell_Reproduction/10.03%3A_Control_of_the_Cell_Cycle/10.3A%3A_Regulation_of_the_Cell_Cycle_by_External_Events.txt |
Learning Objectives
• Differentiate among the molecules that regulate the cell cycle
Regulator Molecules of the Cell Cycle
In addition to the internally controlled checkpoints, there are two groups of intracellular molecules that regulate the cell cycle. These regulatory molecules either promote progress of the cell to the next phase (positive regulation) or halt the cycle (negative regulation). Regulator molecules may act individually or they can influence the activity or production of other regulatory proteins. Therefore, the failure of a single regulator may have almost no effect on the cell cycle, especially if more than one mechanism controls the same event. Conversely, the effect of a deficient or non-functioning regulator can be wide-ranging and possibly fatal to the cell if multiple processes are affected.
Positive Regulation of the Cell Cycle
Two groups of proteins, called cyclins and cyclin-dependent kinases (Cdks), are responsible for the progress of the cell through the various checkpoints. The levels of the four cyclin proteins fluctuate throughout the cell cycle in a predictable pattern. Increases in the concentration of cyclin proteins are triggered by both external and internal signals. After the cell moves to the next stage of the cell cycle, the cyclins that were active in the previous stage are degraded.
Cyclins regulate the cell cycle only when they are tightly bound to Cdks. To be fully active, the Cdk/cyclin complex must also be phosphorylated in specific locations. Like all kinases, Cdks are enzymes (kinases) that phosphorylate other proteins. Phosphorylation activates the protein by changing its shape. The proteins phosphorylated by Cdks are involved in advancing the cell to the next phase.. The levels of Cdk proteins are relatively stable throughout the cell cycle; however, the concentrations of cyclin fluctuate and determine when Cdk/cyclin complexes form. The different cyclins and Cdks bind at specific points in the cell cycle and thus regulate different checkpoints.
Although the cyclins are the main regulatory molecules that determine the forward momentum of the cell cycle, there are several other mechanisms that fine tune the progress of the cycle with negative, rather than positive, effects. These mechanisms essentially block the progression of the cell cycle until problematic conditions are resolved. Molecules that prevent the full activation of Cdks are called Cdk inhibitors. Many of these inhibitor molecules directly or indirectly monitor a particular cell cycle event. The block placed on Cdks by inhibitor molecules will not be removed until the specific event being monitored is completed.
Negative Regulation of the Cell Cycle
The second group of cell cycle regulatory molecules are negative regulators. Negative regulators halt the cell cycle. Remember that in positive regulation, active molecules cause the cycle to progress.
The best understood negative regulatory molecules are retinoblastoma protein (Rb), p53, and p21. Retinoblastoma proteins are a group of tumor-suppressor proteins common in many cells. Much of what is known about cell cycle regulation comes from research conducted with cells that have lost regulatory control. All three of these regulatory proteins were discovered to be damaged or non-functional in cells that had begun to replicate uncontrollably (became cancerous). In each case, the main cause of the unchecked progress through the cell cycle was a faulty copy of the regulatory protein.
Rb, p53, and p21 act primarily at the G1 checkpoint. p53 is a multi-functional protein that has a major impact on the cell’s commitment to division; it acts when there is damaged DNA in cells that are undergoing the preparatory processes during G1. If damaged DNA is detected, p53 halts the cell cycle and recruits enzymes to repair the DNA. If the DNA cannot be repaired, p53 can trigger apoptosis (cell suicide) to prevent the duplication of damaged chromosomes. As p53 levels rise, the production of p21 is triggered. p21 enforces the halt in the cycle dictated by p53 by binding to and inhibiting the activity of the Cdk/cyclin complexes. As a cell is exposed to more stress, higher levels of p53 and p21 accumulate, making it less likely that the cell will move into the S phase.
Rb exerts its regulatory influence on other positive regulator proteins. Rb monitors cell size. In the active, dephosphorylated state, Rb binds to proteins called transcription factors, most commonly to E2F. Transcription factors “turn on” specific genes, allowing the production of proteins encoded by that gene. When Rb is bound to E2F, production of proteins necessary for the G1/S transition is blocked. As the cell increases in size, Rb is slowly phosphorylated until it becomes inactivated. Rb releases E2F, which can now turn on the gene that produces the transition protein and this particular block is removed. For the cell to move past each of the checkpoints, all positive regulators must be “turned on” and all negative regulators must be “turned off.”
Key Points
• Two groups of proteins, cyclins and cyclin-dependent kinases (Cdks), are responsible for promoting the cell cycle.
• Cyclins regulate the cell cycle only when they are bound to Cdks; to be fully active, the Cdk/cyclin complex must be phosphorylated, which allows it to phosphorylate other proteins that advance the cell cycle.
• Negative regulator molecules (Rb, p53, and p21) act primarily at the G1 checkpoint and prevent the cell from moving forward to division until damaged DNA is repaired.
• p53 halts the cell cycle and recruits enzymes to repair damaged DNA; if DNA cannot be repaired, p53 triggers apoptosis to prevent duplication.
• Production of p21 is triggered by p53; p21 halts the cycle by binding to and inhibiting the activity of the Cdk/cyclin complex.
• Dephosphorylated Rb binds to E2F, which halts the cell cycle; when the cell grows, Rb is phosphorylated and releases E2F, which advances the cell cycle.
Key Terms
• cyclin: any of a group of proteins that regulates the cell cycle by forming a complex with kinases
• cyclin-dependent kinase: (CDK) a member of a family of protein kinases first discovered for its role in regulating the cell cycle through phosphorylation
• retinoblastoma protein: (Rb) a group of tumor-suppressor proteins that regulates the cell cycle by monitoring cell size | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/10%3A_Cell_Reproduction/10.03%3A_Control_of_the_Cell_Cycle/10.3C%3A_Regulator_Molecules_of_the_Cell_Cycle.txt |
Learning Objectives
• Explain regulation of the cell cycle by proto-oncogenes
Proto-oncogenes
The genes that code for the positive cell cycle regulators are called proto-oncogenes. Proto-oncogenes are normal genes that, when mutated in certain ways, become oncogenes: genes that cause a cell to become cancerous. There are several ways by which a proto-oncogene can be converted into an oncogene. Consider what might happen to the cell cycle in a cell with a recently-acquired oncogene. In most instances, the alteration of the DNA sequence will result in a less functional (or non-functional) protein. The result is detrimental to the cell and will likely prevent the cell from completing the cell cycle; however, the organism is not harmed because the mutation will not be carried forward. If a cell cannot reproduce, the mutation is not propagated and the damage is minimal.
Occasionally, however, a gene mutation causes a change that increases the activity of a positive regulator. For example, a mutation that allows the Cdk gene to be activated without being partnered with cyclin could push the cell cycle past a checkpoint before all of the required conditions are met. If the resulting daughter cells are too damaged to undergo further cell divisions, the mutation would not be propagated and no harm would come to the organism. However, if the atypical daughter cells are able to undergo further cell divisions, subsequent generations of cells will probably accumulate even more mutations, some possibly in additional genes that regulate the cell cycle.
The Cdk gene in the above example is only one of many genes that are considered proto-oncogenes. In addition to the cell cycle regulatory proteins, any protein that influences the cycle can be altered in such a way as to override cell cycle checkpoints. An oncogene is any gene that, when altered, leads to an increase in the rate of cell cycle progression.
Key Points
• Proto- oncogenes positively regulate the cell cycle.
• Mutations may cause proto-oncogenes to become oncogenes, disrupting normal cell division and causing cancers to form.
• Some mutations prevent the cell from reproducing, which keeps the mutations from being passed on.
• If a mutated cell is able to reproduce because the cell division regulators are damaged, then the mutation will be passed on, possibly accumulating more mutations with successive divisions.
Key Terms
• proto-oncogene: a gene that promotes the specialization and division of normal cells that becomes an oncogene following mutation
• mutation: any heritable change of the base-pair sequence of genetic material
• oncogene: any gene that contributes to the conversion of a normal cell into a cancerous cell when mutated or expressed at high levels
10.4B: Tumor Suppressor Genes
Learning Objectives
• Describe the role played by tumor suppressor genes in the cell cycle
Like proto- oncogenes, many of the negative cell cycle regulatory proteins were discovered in cells that had become cancerous. Tumor suppressor genes are segments of DNA that code for negative regulator proteins: the type of regulators that, when activated, can prevent the cell from undergoing uncontrolled division. The collective function of the best-understood tumor suppressor gene proteins, Rb, p53, and p21, is to put up a roadblock to cell cycle progression until certain events are completed. A cell that carries a mutated form of a negative regulator might not be able to halt the cell cycle if there is a problem. Tumor suppressors are similar to brakes in a vehicle: malfunctioning brakes can contribute to a car crash.
Mutated p53 genes have been identified in more than one-half of all human tumor cells. This discovery is not surprising in light of the multiple roles that the p53 protein plays at the G1 checkpoint. A cell with a faulty p53 may fail to detect errors present in the genomic DNA. Even if a partially-functional p53 does identify the mutations, it may no longer be able to signal the necessary DNA repair enzymes. Either way, damaged DNA will remain uncorrected. At this point, a functional p53 will deem the cell unsalvageable and trigger programmed cell death (apoptosis). The damaged version of p53 found in cancer cells, however, cannot trigger apoptosis.
The loss of p53 function has other repercussions for the cell cycle. Mutated p53 might lose its ability to trigger p21 production. Without adequate levels of p21, there is no effective block on Cdk activation. Essentially, without a fully functional p53, the G1 checkpoint is severely compromised and the cell proceeds directly from G1 to S regardless of internal and external conditions. At the completion of this shortened cell cycle, two daughter cells are produced that have inherited the mutated p53 gene. Given the non-optimal conditions under which the parent cell reproduced, it is likely that the daughter cells will have acquired other mutations in addition to the faulty tumor suppressor gene. Cells such as these daughter cells quickly accumulate both oncogenes and non-functional tumor suppressor genes. Again, the result is tumor growth.
Key Points
• Tumor suppressor genes are segments of DNA that code for negative regulator proteins, which keep the cell from undergoing uncontrolled division.
• Mutated p53 genes are believed to be responsible for causing tumor growth because they turn off the regulatory mechanisms that keep cells from dividing out of control.
• Sometimes cells with negative regulators can halt their transmission by inducing pre-programmed cell death called apoptosis.
• Without a fully functional p53, the G1 checkpoint of interphase is severely compromised and the cell proceeds directly from G1 to S; this creates two daughter cells that have inherited the mutated p53 gene.
Key Terms
• apoptosis: a process of programmed cell death | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/10%3A_Cell_Reproduction/10.04%3A_Cancer_and_the_Cell_Cycle/10.4A%3A_Proto-oncogenes.txt |
Learning Objectives
• Describe the process of binary fission in prokaryotes
Prokaryotes, such as bacteria, propagate by binary fission. For unicellular organisms, cell division is the only method used to produce new individuals. In both prokaryotic and eukaryotic cells, the outcome of cell reproduction is a pair of daughter cells that are genetically identical to the parent cell. In unicellular organisms, daughter cells are individuals.
Due to the relative simplicity of the prokaryotes, the cell division process, or binary fission, is a less complicated and much more rapid process than cell division in eukaryotes. The single, circular DNA chromosome of bacteria is not enclosed in a nucleus, but instead occupies a specific location, the nucleoid, within the cell. Although the DNA of the nucleoid is associated with proteins that aid in packaging the molecule into a compact size, there are no histone proteins and thus, no nucleosomes in prokaryotes. The packing proteins of bacteria are, however, related to the cohesin and condensin proteins involved in the chromosome compaction of eukaryotes.
The bacterial chromosome is attached to the plasma membrane at about the midpoint of the cell. The starting point of replication, the origin, is close to the binding site of the chromosome at the plasma membrane. Replication of the DNA is bidirectional, moving away from the origin on both strands of the loop simultaneously. As the new double strands are formed, each origin point moves away from the cell wall attachment toward the opposite ends of the cell. As the cell elongates, the growing membrane aids in the transport of the chromosomes. After the chromosomes have cleared the midpoint of the elongated cell, cytoplasmic separation begins. The formation of a ring composed of repeating units of a protein, FtsZ, directs the partition between the nucleoids. Formation of the FtsZ ring triggers the accumulation of other proteins that work together to recruit new membrane and cell wall materials to the site. A septum is formed between the nucleoids, extending gradually from the periphery toward the center of the cell. When the new cell walls are in place, the daughter cells separate.
Mitotic Spindle Apparatus
The precise timing and formation of the mitotic spindle is critical to the success of eukaryotic cell division. Prokaryotic cells, on the other hand, do not undergo karyokinesis and, therefore, have no need for a mitotic spindle. However, the FtsZ protein that plays such a vital role in prokaryotic cytokinesis is structurally and functionally very similar to tubulin, the building block of the microtubules that make up the mitotic spindle fibers that are necessary for eukaryotes. FtsZ proteins can form filaments, rings, and other three-dimensional structures that resemble the way tubulin forms microtubules, centrioles, and various cytoskeletal components. In addition, both FtsZ and tubulin employ the same energy source, GTP (guanosine triphosphate), to rapidly assemble and disassemble complex structures.
FtsZ and tubulin are homologous structures derived from common evolutionary origins. In this example, FtsZ is the ancestor protein to tubulin (a modern protein). While both proteins are found in extant organisms, tubulin function has evolved and diversified tremendously since evolving from its FtsZ prokaryotic origin. A survey of mitotic assembly components found in present-day unicellular eukaryotes reveals crucial intermediary steps to the complex membrane-enclosed genomes of multicellular eukaryotes.
Key Points
• In bacterial replication, the DNA is attached to the plasma membrane at about the midpoint of the cell.
• The origin, or starting point of bacterial replication, is close to the binding site of the DNA to the plasma membrane.
• Replication of the bacterial DNA is bidirectional, which means it moves away from the origin on both strands simultaneously.
• The formation of the FtsZ ring, a ring composed of repeating units of protein, triggers the accumulation of other proteins that work together to acquire and bring new membrane and cell wall materials to the site.
• When new cell walls are in place, due to the formation of a septum, the daughter cells separate to form individual cells.
Key Terms
• mitotic spindle: the apparatus that orchestrates the movement of DNA during mitosis
• karyokinesis: (mitosis) the first portion of mitotic phase where division of the cell nucleus takes place
• binary fission: the process whereby a cell divides asexually to produce two daughter cells | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/10%3A_Cell_Reproduction/10.05%3A_Prokaryotic_Cell_Division/10.5A%3A_Binary_Fission.txt |
Learning Objectives
• Describe the importance of meiosis in sexual reproduction
Introduction: Meiosis and Sexual Reproduction
The ability to reproduce in kind is a basic characteristic of all living things. In kind means that the offspring of any organism closely resemble their parent or parents. Sexual reproduction requires fertilization: the union of two cells from two individual organisms. Haploid cells contain one set of chromosomes. Cells containing two sets of chromosomes are called diploid. The number of sets of chromosomes in a cell is called its ploidy level. If the reproductive cycle is to continue, then the diploid cell must somehow reduce its number of chromosome sets before fertilization can occur again or there will be a continual doubling in the number of chromosome sets in every generation. Therefore, sexual reproduction includes a nuclear division that reduces the number of chromosome sets.
Sexual reproduction is the production of haploid cells (gametes) and the fusion (fertilization) of two gametes to form a single, unique diploid cell called a zygote. All animals and most plants produce these gametes, or eggs and sperm. In most plants and animals, through tens of rounds of mitotic cell division, this diploid cell will develop into an adult organism.
Haploid cells that are part of the sexual reproductive cycle are produced by a type of cell division called meiosis. Meiosis employs many of the same mechanisms as mitosis. However, the starting nucleus is always diploid and the nuclei that result at the end of a meiotic cell division are haploid, so the resulting cells have half the chromosomes as the original. To achieve this reduction in chromosomes, meiosis consists of one round of chromosome duplication and two rounds of nuclear division. Because the events that occur during each of the division stages are analogous to the events of mitosis, the same stage names are assigned. However, because there are two rounds of division, the major process and the stages are designated with a “I” or a “II.” Thus, meiosis I is the first round of meiotic division and consists of prophase I, prometaphase I, and so on. Meiosis II, the second round of meiotic division, includes prophase II, prometaphase II, and so on.
Key Points
• Sexual reproduction is the production of haploid cells and the fusion of two of those cells to form a diploid cell.
• Before sexual reproduction can occur, the number of chromosomes in a diploid cell must decrease by half.
• Meiosis produces cells with half the number of chromosomes as the original cell.
• Haploid cells used in sexual reproduction, gametes, are formed during meiosis, which consists of one round of chromosome replication and two rounds of nuclear division.
• Meiosis I is the first round of meiotic division, while meiosis II is the second round.
Key Terms
• haploid: of a cell having a single set of unpaired chromosomes
• gamete: a reproductive cell, male (sperm) or female (egg), that has only half the usual number of chromosomes
• diploid: of a cell, having a pair of each type of chromosome, one of the pair being derived from the ovum and the other from the spermatozoon | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/11%3A_Meiosis_and_Sexual_Reproduction/11.01%3A_The_Process_of_Meiosis_-_Introduction_to_Meiosis.txt |
Learning Objectives
• Describe the stages and results of meiosis I
Meiosis I
Meiosis is preceded by an interphase consisting of three stages. The G1 phase (also called the first gap phase) initiates this stage and is focused on cell growth. The S phase is next, during which the DNA of the chromosomes is replicated. This replication produces two identical copies, called sister chromatids, that are held together at the centromere by cohesin proteins. The centrosomes, which are the structures that organize the microtubules of the meiotic spindle, also replicate. Finally, during the G2 phase (also called the second gap phase), the cell undergoes the final preparations for meiosis.
Prophase I
During prophase I, chromosomes condense and become visible inside the nucleus. As the nuclear envelope begins to break down, homologous chromosomes move closer together. The synaptonemal complex, a lattice of proteins between the homologous chromosomes, forms at specific locations, spreading to cover the entire length of the chromosomes. The tight pairing of the homologous chromosomes is called synapsis. In synapsis, the genes on the chromatids of the homologous chromosomes are aligned with each other. The synaptonemal complex also supports the exchange of chromosomal segments between non-sister homologous chromatids in a process called crossing over. The crossover events are the first source of genetic variation produced by meiosis. A single crossover event between homologous non-sister chromatids leads to an exchange of DNA between chromosomes. Following crossover, the synaptonemal complex breaks down and the cohesin connection between homologous pairs is also removed. At the end of prophase I, the pairs are held together only at the chiasmata; they are called tetrads because the four sister chromatids of each pair of homologous chromosomes are now visible.
Prometaphase I
The key event in prometaphase I is the formation of the spindle fiber apparatus where spindle fiber microtubules attach to the kinetochore proteins at the centromeres. Microtubules grow from centrosomes placed at opposite poles of the cell. The microtubules move toward the middle of the cell and attach to one of the two fused homologous chromosomes at the kinetochores. At the end of prometaphase I, each tetrad is attached to microtubules from both poles, with one homologous chromosome facing each pole. In addition, the nuclear membrane has broken down entirely.
Metaphase I
During metaphase I, the tetrads move to the metaphase plate with kinetochores facing opposite poles. The homologous pairs orient themselves randomly at the equator. This event is the second mechanism that introduces variation into the gametes or spores. In each cell that undergoes meiosis, the arrangement of the tetrads is different. The number of variations is dependent on the number of chromosomes making up a set. There are two possibilities for orientation at the metaphase plate. The possible number of alignments, therefore, equals 2n, where n is the number of chromosomes per set. Given these two mechanisms, it is highly unlikely that any two haploid cells resulting from meiosis will have the same genetic composition.
Anaphase I
In anaphase I, the microtubules pull the attached chromosomes apart. The sister chromatids remain tightly bound together at the centromere. The chiasmata are broken in anaphase I as the microtubules attached to the fused kinetochores pull the homologous chromosomes apart.
Telophase I and Cytokinesis
In telophase I, the separated chromosomes arrive at opposite poles. In some organisms, the chromosomes decondense and nuclear envelopes form around the chromatids in telophase I. Then cytokinesis, the physical separation of the cytoplasmic components into two daughter cells, occurs without reformation of the nuclei. In nearly all species of animals and some fungi, cytokinesis separates the cell contents via a cleavage furrow (constriction of the actin ring that leads to cytoplasmic division). In plants, a cell plate is formed during cell cytokinesis by Golgi vesicles fusing at the metaphase plate. This cell plate will ultimately lead to the formation of cell walls that separate the two daughter cells.
Two haploid cells are the end result of the first meiotic division. The cells are haploid because at each pole there is just one of each pair of the homologous chromosomes. Therefore, only one full set of the chromosomes is present. Although there is only one chromosome set, each homolog still consists of two sister chromatids.
Key Points
• Meiosis is preceded by interphase which consists of the G1 phase (growth), the S phase ( DNA replication), and the G2 phase.
• During prophase I, the homologous chromosomes condense and become visible as the x shape we know, pair up to form a tetrad, and exchange genetic material by crossing over.
• During prometaphase I, microtubules attach at the chromosomes’ kinetochores and the nuclear envelope breaks down.
• In metaphase I, the tetrads line themselves up at the metaphase plate and homologous pairs orient themselves randomly.
• In anaphase I, centromeres break down and homologous chromosomes separate.
• In telophase I, chromosomes move to opposite poles; during cytokinesis the cell separates into two haploid cells.
Key Terms
• crossing over: the exchange of genetic material between homologous chromosomes that results in recombinant chromosomes
• tetrad: two pairs of sister chromatids (a dyad pair) aligned in a certain way and often on the equatorial plane during the meiosis process
• chromatid: either of the two strands of a chromosome that separate during meiosis | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/11%3A_Meiosis_and_Sexual_Reproduction/11.02%3A_The_Process_of_Meiosis_-_Meiosis_I.txt |
Learning Objectives
• Describe the stages and results of Meiosis II
Meiosis II
Meiosis II initiates immediately after cytokinesis, usually before the chromosomes have fully decondensed. In contrast to meiosis I, meiosis II resembles a normal mitosis. In some species, cells enter a brief interphase, or interkinesis, before entering meiosis II. Interkinesis lacks an S phase, so chromosomes are not duplicated. The two cells produced in meiosis I go through the events of meiosis II together. During meiosis II, the sister chromatids within the two daughter cells separate, forming four new haploid gametes. The mechanics of meiosis II is similar to mitosis, except that each dividing cell has only one set of homologous chromosomes.
Prophase II
If the chromosomes decondensed in telophase I, they condense again. If nuclear envelopes were formed, they fragment into vesicles. The centrosomes that were duplicated during interphase I move away from each other toward opposite poles and new spindles are formed.
Prometaphase II
The nuclear envelopes are completely broken down and the spindle is fully formed. Each sister chromatid forms an individual kinetochore that attaches to microtubules from opposite poles.
Metaphase II
The sister chromatids are maximally condensed and aligned at the equator of the cell.
Anaphase II
The sister chromatids are pulled apart by the kinetochore microtubules and move toward opposite poles. Non-kinetochore microtubules elongate the cell.
Telophase II and Cytokinesis
The chromosomes arrive at opposite poles and begin to decondense. Nuclear envelopes form around the chromosomes. Cytokinesis separates the two cells into four unique haploid cells. At this point, the newly-formed nuclei are both haploid. The cells produced are genetically unique because of the random assortment of paternal and maternal homologs and because of the recombining of maternal and paternal segments of chromosomes (with their sets of genes) that occurs during crossover.
Key Points
• During prophase II, chromsomes condense again, centrosomes that were duplicated during interphase I move away from each other toward opposite poles, and new spindles are formed.
• During prometaphase II, the nuclear envelopes are completely broken down, and each sister chromatid forms an individual kinetochore that attaches to microtubules from opposite poles.
• During metaphase II, sister chromatids are condensed and aligned at the equator of the cell.
• During anaphase II sister chromatids are pulled apart by the kinetochore microtubules and move toward opposite poles.
• During telophase II and cytokinesis, chromosomes arrive at opposite poles and begin to decondense; the two cells divide into four unique haploid cells.
Key Terms
• meiosis II: the second part of the meiotic process; the end result is production of four haploid cells from the two haploid cells produced in meiosis I
11.04: The Process of Meiosis - Comparing Meiosis and Mitosis
Learning Objectives
• Compare and contrast mitosis and meiosis
Mitosis and meiosis are both forms of division of the nucleus in eukaryotic cells. They share some similarities, but also exhibit distinct differences that lead to very different outcomes. The purpose of mitosis is cell regeneration, growth, and asexual reproduction,while the purpose of meiosis is the production of gametes for sexual reproduction. Mitosis is a single nuclear division that results in two nuclei that are usually partitioned into two new daughter cells. The nuclei resulting from a mitotic division are genetically identical to the original nucleus. They have the same number of sets of chromosomes, one set in the case of haploid cells and two sets in the case of diploid cells. In most plants and all animal species, it is typically diploid cells that undergo mitosis to form new diploid cells. In contrast, meiosis consists of two nuclear divisions resulting in four nuclei that are usually partitioned into four new haploid daughter cells. The nuclei resulting from meiosis are not genetically identical and they contain one chromosome set only. This is half the number of chromosome sets in the original cell, which is diploid.
The main differences between mitosis and meiosis occur in meiosis I. In meiosis I, the homologous chromosome pairs become associated with each other and are bound together with the synaptonemal complex. Chiasmata develop and crossover occurs between homologous chromosomes, which then line up along the metaphase plate in tetrads with kinetochore fibers from opposite spindle poles attached to each kinetochore of a homolog in a tetrad. All of these events occur only in meiosis I.
When the tetrad is broken up and the homologous chromosomes move to opposite poles, the ploidy level is reduced from two to one. For this reason, meiosis I is referred to as a reduction division. There is no such reduction in ploidy level during mitosis.
Meiosis II is much more similar to a mitotic division. In this case, the duplicated chromosomes (only one set, as the homologous pairs have now been separated into two different cells) line up on the metaphase plate with divided kinetochores attached to kinetochore fibers from opposite poles. During anaphase II and mitotic anaphase, the kinetochores divide and sister chromatids, now referred to as chromosomes, are pulled to opposite poles. The two daughter cells of mitosis, however, are identical, unlike the daughter cells produced by meiosis. They are different because there has been at least one crossover per chromosome. Meiosis II is not a reduction division because, although there are fewer copies of the genome in the resulting cells, there is still one set of chromosomes, as there was at the end of meiosis I. Meiosis II is, therefore, referred to as equatorial division.
Key Points
• For the most part, in mitosis, diploid cells are partitioned into two new diploid cells, while in meiosis, diploid cells are partitioned into four new haploid cells.
• In mitosis, the daughter cells have the same number of chromosomes as the parent cell, while in meiosis, the daughter cells have half the number of chromosomes as the parent.
• The daughter cells produced by mitosis are identical, whereas the daughter cells produced by meiosis are different because crossing over has occurred.
• The events that occur in meiosis but not mitosis include homologous chromosomes pairing up, crossing over, and lining up along the metaphase plate in tetrads.
• Meiosis II and mitosis are not reduction division like meiosis I because the number of chromosomes remains the same; therefore, meiosis II is referred to as equatorial division.
• When the homologous chromosomes separate and move to opposite poles during meiosis I, the ploidy level is reduced from two to one, which is referred to as a reduction division.
Key Terms
• reduction division: the first of the two divisions of meiosis, a type of cell division
• ploidy: the number of homologous sets of chromosomes in a cell
• equatorial division: a process of nuclear division in which each chromosome divides equally such that the number of chromosomes remains the same from parent to daughter cells | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/11%3A_Meiosis_and_Sexual_Reproduction/11.03%3A_The_Process_of_Meiosis_-_Meiosis_II.txt |
Learning Objectives
• Describe the benefits of sexual reproduction
An Introduction to Sexual Reproduction
Sexual reproduction was an early evolutionary innovation after the appearance of eukaryotic cells. During sexual reproduction, the genetic material of two individuals is combined to produce genetically-diverse offspring that differ from their parents. The fact that most eukaryotes reproduce sexually is evidence of its evolutionary success. In many animals, it is actually the only mode of reproduction. The genetic diversity of sexually-produced offspring is thought to give species a better chance of surviving in an unpredictable or changing environment.
Scientists recognize some real disadvantages to sexual reproduction. On the surface, creating offspring that are genetic clones of the parent appears to be a better system. If the parent organism is successfully occupying a habitat, offspring with the same traits would be similarly successful. Species that reproduce sexually must maintain two different types of individuals, males and females, which can limit the ability to colonize new habitats as both sexes must be present. Therefore, there is an obvious benefit to an organism that can produce offspring whenever circumstances are favorable by asexual budding, fragmentation, or asexual eggs. These methods of asexual reproduction do not require another organism of the opposite sex. Indeed, some organisms that lead a solitary lifestyle have retained the ability to reproduce asexually. In addition, in asexual populations, every individual is capable of reproduction. In sexual populations, the males are not producing the offspring themselves. In theory, an asexual population could grow twice as fast.
Nevertheless, multicellular organisms that exclusively depend on asexual reproduction are exceedingly rare. Why is sexuality (and meiosis ) so common? This is one of the important unanswered questions in biology and has been the focus of much research beginning in the latter half of the twentieth century. There are several possible explanations, one of which is that the variation that sexual reproduction creates among offspring is very important to the survival and reproduction of the population. Thus, on average, a sexually-reproducing population will leave more descendants than an otherwise similar asexually-reproducing population. The only source of variation in asexual organisms is mutation. This is the ultimate source of variation in sexual organisms, but, in addition, those different mutations are continually reshuffled from one generation to the next when different parents combine their unique genomes and the genes are mixed into different combinations by the process of meiosis. Meiosis is the division of the contents of the nucleus, dividing the chromosomes among gametes.
The process of meiosis produces unique reproductive cells called gametes, which have half the number of chromosomes as the parent cell. Fertilization, the fusion of haploid gametes from two individuals, restores the diploid condition. Thus, sexually-reproducing organisms alternate between haploid and diploid stages. However, the ways in which reproductive cells are produced and the timing between meiosis and fertilization vary greatly. There are three main categories of sexual life cycles: diploid-dominant, demonstrated by most animals; haploid-dominant, demonstrated by all fungi and some algae; and the alternation of generations, demonstrated by plants and some algae.
The Red Queen Hypothesis
It is not in dispute that sexual reproduction provides evolutionary advantages to organisms that employ this mechanism to produce offspring. But why, even in the face of fairly stable conditions, does sexual reproduction persist when it is more difficult and costly for individual organisms? Variation is the outcome of sexual reproduction, but why are ongoing variations necessary? Possible answers to these questions are explained in the Red Queen hypothesis, first proposed by Leigh Van Valen in 1973.
All species co-evolve with other organisms; for example, predators evolve with their prey and parasites evolve with their hosts. Each tiny advantage gained by favorable variation gives a species an edge over close competitors, predators, parasites, or even prey. The only method that will allow a co-evolving species to maintain its own share of the resources is to also continually improve its fitness. As one species gains an advantage, this increases selection on the other species; they must also develop an advantage or they will be out-competed. No single species progresses too far ahead because genetic variation among the progeny of sexual reproduction provides all species with a mechanism to improve rapidly. Species that cannot keep up become extinct. The Red Queen’s catchphrase was, “It takes all the running you can do to stay in the same place.” This is an apt description of co-evolution between competing species.
Key Points
• The variation that sexual reproduction creates among offspring is very important to the survival and reproduction of the population.
• In sexual reproduction, different mutations are continually reshuffled from one generation to the next when different parents combine their unique genomes; this results in an increase of genetic diversity.
• On average, a sexually-reproducing population will leave more offspring than an otherwise similar asexually-reproducing population.
Key Terms
• sexual reproduction: Sexual reproduction is the creation of a new organism by combining the genetic material of two organisms. There are two main processes during sexual reproduction: meiosis, involving the halving of the number of chromosomes, and fertilization, involving the fusion of two gametes and the restoration of the original number of chromosomes.
• asexual reproduction: any form of reproduction that involves neither meiosis nor fusion of gametes | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/11%3A_Meiosis_and_Sexual_Reproduction/11.05%3A_Sexual_Reproduction_-_Advantages_and_Disadvantages_of_Sexual_Reproduction.txt |
Learning Objectives
• Explain the life cycles in sexual reproduction
In sexual reproduction, the genetic material of two individuals is combined to produce genetically diverse offspring that differ from their parents. Fertilization and meiosis alternate in sexual life cycles. What happens between these two events depends upon the organism. The process of meiosis, the division of the contents of the nucleus that divides the chromosomes among gametes, reduces the chromosome number by half, while fertilization, the joining of two haploid gametes, restores the diploid condition. There are three main categories of life cycles in eukaryotic organisms: diploid-dominant, haploid-dominant, and alternation of generations.
Diploid-Dominant Life Cycle
In the diploid-dominant life cycle, the multicellular diploid stage is the most obvious life stage, as occurs with most animals, including humans. Nearly all animals employ a diploid-dominant life cycle strategy in which the only haploid cells produced by the organism are the gametes. Early in the development of the embryo, specialized diploid cells, called germ cells, are produced within the gonads (e.g. testes and ovaries). Germ cells are capable of mitosis to perpetuate the cell line and meiosis to produce gametes. Once the haploid gametes are formed, they lose the ability to divide again. There is no multicellular haploid life stage. Fertilization occurs with the fusion of two gametes, usually from different individuals, restoring the diploid state.
Haploid-Dominant Life Cycle
Within haploid-dominant life cycles, the multicellular haploid stage is the most obvious life stage. Most fungi and algae employ a life cycle type in which the “body” of the organism, the ecologically important part of the life cycle, is haploid. The haploid cells that make up the tissues of the dominant multicellular stage are formed by mitosis. During sexual reproduction, specialized haploid cells from two individuals, designated the (+) and (−) mating types, join to form a diploid zygote. The zygote immediately undergoes meiosis to form four haploid cells called spores. Although haploid like the “parents,” these spores contain a new genetic combination from two parents. The spores can remain dormant for various time periods. Eventually, when conditions are conducive, the spores form multicellular haploid structures by many rounds of mitosis.
Alternation of Generations
The third life-cycle type, employed by some algae and all plants, is a blend of the haploid-dominant and diploid-dominant extremes. Species with alternation of generations have both haploid and diploid multicellular organisms as part of their life cycle. The haploid multicellular plants are called gametophytes because they produce gametes from specialized cells. Meiosis is not directly involved in the production of gametes because the organism that produces the gametes is already a haploid. Fertilization between the gametes forms a diploid zygote. The zygote will undergo many rounds of mitosis and give rise to a diploid multicellular plant called a sporophyte. Specialized cells of the sporophyte will undergo meiosis and produce haploid spores. The spores will subsequently develop into the gametophytes.
Although all plants utilize some version of the alternation of generations, the relative size of the sporophyte and the gametophyte and the relationship between them vary greatly. In plants such as moss, the gametophyte organism is the free-living plant, while the sporophyte is physically dependent on the gametophyte. In other plants, such as ferns, both the gametophyte and sporophyte plants are free-living; however, the sporophyte is much larger. In seed plants, such as magnolia trees and daisies, the gametophyte is composed of only a few cells and, in the case of the female gametophyte, is completely retained within the sporophyte.
Sexual reproduction takes many forms in multicellular organisms. However, at some point in each type of life cycle, meiosis produces haploid cells that will fuse with the haploid cell of another organism. The mechanisms of variation (crossover, random assortment of homologous chromosomes, and random fertilization) are present in all versions of sexual reproduction. The fact that nearly every multicellular organism on earth employs sexual reproduction is strong evidence for the benefits of producing offspring with unique gene combinations, although there are other possible benefits as well.
Key Points
• In the diploid – dominant cycle, the multicellular diploid stage is the most obvious life stage; the only haploid cells produced by the organism are the gametes.
• Most fungi and algae employ a haploid-dominant life cycle type in which the “body” of the organism is haploid; specialized haploid cells from two individuals join to form a diploid zygote.
• Observed in all plants and some algae, species with alternation of generations have both haploid and diploid multicellular organisms as part of their life cycle.
Key Terms
• zygote: a diploid fertilized egg cell
• gametophyte: a plant (or the haploid phase in its life cycle) that produces gametes by mitosis in order to produce a zygote
• sporophyte: a plant (or the diploid phase in its life cycle) that produces spores by meiosis in order to produce gametophytes | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/11%3A_Meiosis_and_Sexual_Reproduction/11.06%3A_Sexual_Reproduction_-_Life_Cycles_of_Sexually_Reproducing_Organisms.txt |
Learning Objectives
• Describe the traits of pea plants that were studied by Mendel
Gregor Mendel and the Study of Genetics
Genetics is the study of heredity, or the passing of traits from parents to offspring. Gregor Johann Mendel set the framework for genetics long before chromosomes or genes had been identified, at a time when meiosis was not well understood. For his work, Mendel is often referred to as the “father of modern genetics. ” Mendel selected a simple biological system, garden peas, and conducted methodical, quantitative analyses using large sample sizes.
Mendel entered the Augustinian St. Thomas’s Abbey and began his training as a priest. He began studying heredity using mice, but his bishop did not like one of his friars studying animal sex, so he switched to plants. Mendel grew and studied around 29,000 garden pea plants in a monastery’s garden, where he analyzed seven characteristics of the garden pea plants: flower color (purple or white), seed texture (wrinkled or round), seed color (yellow or green), stem length (long or short), pod color (yellow or green), pod texture (inflated or constricted), and flower position (axial or terminal). Based on the appearance, or phenotypes, of the seven traits, Mendel developed genotypes for those traits.
Because of Mendel’s work, the fundamental principles of heredity were revealed, which are often referred to as Mendel’s Laws of Inheritance. We now know that genes, carried on chromosomes, are the basic functional units of heredity with the capability to be replicated, expressed, or mutated. Today, the postulates put forth by Mendel form the basis of classical, or Mendelian, genetics. Not all genes are transmitted from parents to offspring according to Mendelian genetics, but Mendel’s experiments serve as an excellent starting point for thinking about inheritance.
Mendel made all of his observations and findings crossing individual plants. We can now view a human karyotype of all of the chromosomes in an individual to visualize chromosomal abnormalities in offspring, even before birth. Shortly after Mendel proposed that traits were determined by what are now known as genes, other researchers observed that different traits were often inherited together, and thereby deduced that the genes were physically linked by being located on the same chromosome. Mendel’s work was the beginning of many of the advances in molecular biology over the years.
Key Points
• Mendel studied seven characteristics of the garden pea plants: flower color, seed texture, seed color, stem length, pod color, pod texture, and flower position to develop his Laws of Inheritance.
• Genetics is the study of genes passed from parents to offspring.
• Genes are the basic fundamental units of heredity.
Key Terms
• genetics: The branch of biology that deals with the transmission and variation of inherited characteristics, in particular chromosomes and DNA.
12.1B: Mendels Model System
Learning Objectives
• Describe the scientific reasons for the success of Mendel’s experimental work
Mendel’s Model System
Mendel’s seminal work was accomplished using the garden pea, Pisum sativum, to study inheritance. Pea plant reproduction is easily manipulated; large quantities of garden peas could be cultivated simultaneously, allowing Mendel to conclude that his results did not occur simply by chance. The garden pea also grows to maturity within one season; several generations could be evaluated over a relatively short time.
Pea plants have both male and female parts and can easily be grown in large numbers. For this reason, garden pea plants can either self-pollinate or cross-pollinate with other pea plants. In the absence of outside manipulation, this species naturally self-fertilizes: ova (the eggs) within individual flowers are fertilized by pollen (containing the sperm cell) from the same flower. The sperm and the eggs that produce the next generation of plants both come from the same parent. What’s more, the flower petals remain sealed tightly until after pollination, preventing pollination from other plants. The result is highly inbred, or “true-breeding,” pea plants. These are plants that always produce offspring that look like the parent. Today, we know that these “true-breeding” plants are homozygous for most traits.
A gardener or researcher, such as Mendel, can cross-pollinate these same plants by manually applying sperm from one plant to the pistil (containing the ova) of another plant. Now the sperm and eggs come from different parent plants. When Mendel cross-pollinated a true-breeding plant that only produced yellow peas with a true-breeding plant that only produced green peas, he found that the first generation of offspring is always all yellow peas. The green pea trait did not show up. However, if this first generation of yellow pea plants were allowed to self-pollinate, the following or second generation had a ratio of 3:1 yellow to green peas.
In this and all the other pea plant traits Mendel followed, one form of the trait was “dominant” over another so it masked the presence of the other “recessive” form in the first generation after cross-breeding two homozygous plants.. Even if the phenotype (visible form) is hidden, the genotype (allele controlling that form of the trait) can be passed on to next generation and produce the recessive form in the second generation. By experimenting with true-breeding pea plants, Mendel avoided the appearance of unexpected (recombinant) traits in offspring that might occur if the plants were not true breeding.
Key Points
• Mendel used true-breeding plants in his experiments. These plants, when self-fertilized, always produce offspring with the same phenotype.
• Pea plants are easily manipulated, grow in one season, and can be grown in large quantities; these qualities allowed Mendel to conduct methodical, quantitative analyses using large sample sizes.
• Based on his experiments with the garden peas, Mendel found that one phenotype was always dominant over another recessive phenotype for the same trait.
Key Terms
• phenotype: the observable characteristics of an organism, often resulting from its genetic information or a combination of genetic information and environmental factors
• genotype: the specific genetic information of a cell or organism, usually a description of the allele or alleles relating to a specific gene.
• true-breeding plant: a plant that always produces offspring of the same phenotype when self-fertilized; one that is homozygous for the trait being followed.
12.1C: Mendelian Crosses
Learning Objectives
• Identify Mendelian crosses
Mendelian Crosses
Mendel performed crosses, which involved mating two true-breeding individuals that have different traits. In the pea, which is a naturally self-pollinating plant, this is done by manually transferring pollen from the anther of a mature pea plant of one variety to the stigma of a separate mature pea plant of the second variety. In plants, pollen carries the male gametes (sperm) to the stigma, a sticky organ that traps pollen and allows the sperm to move down the pistil to the female gametes (ova) below. To prevent the pea plant that was receiving pollen from self-fertilizing and confounding his results, Mendel painstakingly removed all of the anthers from the plant’s flowers before they had a chance to mature.
Plants used in first-generation crosses were called P0, or parental generation one, plants. Mendel collected the seeds belonging to the P0 plants that resulted from each cross and grew them the following season. These offspring were called the F1, or the first filial (filial = offspring, daughter or son), generation. Once Mendel examined the characteristics in the F1generation of plants, he allowed them to self-fertilize naturally. He then collected and grew the seeds from the F1 plants to produce the F2, or second filial, generation. Mendel’s experiments extended beyond the F2 generation to the F3 and F4generations, and so on, but it was the ratio of characteristics in the P0−F1−F2 generations that were the most intriguing and became the basis for Mendel’s postulates.
Key Points
• Mendel carefully controlled his experiments by removing the anthers from the pea plants before they matured.
• First generation pea plants were called parental generation, P0, while the following generations were called filial, Fn, where n is the number of generations from P0.
• The ratio of characteristics in the P0−F1−F2 generations became the basis for Mendel’s postulates.
Key Terms
• filial: of a generation or generations descending from a specific previous one
• parental: of the generation of organisms that produce a hybrid | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/12%3A_Mendel's_Experiments_and_Heredity/12.01%3A_Mendels_Experiments_and_the_Laws_of_Probability/12.1A%3A_Introduction_to_Mendelian_Inheritance.txt |
Learning Objectives
• Evaluate the results of F1 and F2 generations from Mendelian crosses of peas
Garden Pea Characteristics Revealed the Basics of Heredity
To fully examine each of the seven traits in garden peas, Mendel generated large numbers of F1 and F2 plants, reporting results from 19,959 F2 plants alone. His findings were consistent.
What results did Mendel find in his crosses for flower color? First, Mendel confirmed that he had plants that bred true for white or violet flower color. Regardless of how many generations Mendel examined, all self-crossed offspring of parents with white flowers had white flowers, and all self-crossed offspring of parents with violet flowers had violet flowers. In addition, Mendel confirmed that, other than flower color, the pea plants were physically identical.
Once these validations were complete, Mendel applied the pollen from a plant with violet flowers to the stigma of a plant with white flowers. After gathering and sowing the seeds that resulted from this cross, Mendel found that 100 percent of the F1hybrid generation had violet flowers. Conventional wisdom at that time would have predicted the hybrid flowers to be pale violet or for hybrid plants to have equal numbers of white and violet flowers. In other words, the contrasting parental traits were expected to blend in the offspring. Instead, Mendel’s results demonstrated that the white flower trait in the F1 generation had completely disappeared.
Importantly, Mendel did not stop his experimentation there. He allowed the F1 plants to self-fertilize and found that, of F2-generation plants, 705 had violet flowers and 224 had white flowers. This was a ratio of 3.15 violet flowers per one white flower, or approximately 3:1. When Mendel transferred pollen from a plant with violet flowers to the stigma of a plant with white flowers and vice versa, he obtained about the same ratio regardless of which parent, male or female, contributed which trait. This is called a reciprocal cross: a paired cross in which the respective traits of the male and female in one cross become the respective traits of the female and male in the other cross. For the other six characteristics Mendel examined, the F1 and F2generations behaved in the same way as they had for flower color. One of the two traits would disappear completely from the F1 generation only to reappear in the F2 generation at a ratio of approximately 3:1.
Upon compiling his results for many thousands of plants, Mendel concluded that the characteristics could be divided into expressed and latent traits. He called these, respectively, dominant and recessive traits. Dominant traits are those that are inherited unchanged in a hybridization. Recessive traits become latent, or disappear, in the offspring of a hybridization. The recessive trait does, however, reappear in the progeny of the hybrid offspring. An example of a dominant trait is the violet-flower trait. For this same characteristic (flower color), white-colored flowers are a recessive trait. The fact that the recessive trait reappeared in the F2 generation meant that the traits remained separate (not blended) in the plants of the F1 generation. Mendel also proposed that plants possessed two copies of the trait for the flower-color characteristic and that each parent transmitted one of its two copies to its offspring, where they came together. Moreover, the physical observation of a dominant trait could mean that the genetic composition of the organism included two dominant versions of the characteristic or that it included one dominant and one recessive version. Conversely, the observation of a recessive trait meant that the organism lacked any dominant versions of this characteristic.
Key Points
• Dominant traits are inherited unchanged from one generation to the next.
• Recessive traits disappear in the first filial generation, but reappear in the second filial generation at a ratio of 3:1, dominant:recessive.
• In the F1 generation, Mendel found that one of the two options for each trait had disappeared (all offspring were identical phenotypes), while in the F2 generation, the trait reappeared in 1/4 of the offspring (a 3:1 ratio).
Key Terms
• hybrid: offspring resulting from cross-breeding different entities, e.g. two different species or two purebred parent strains
• recessive: able to be covered up by a dominant trait
• dominant: a relationship between alleles of a gene, in which one allele masks the expression (phenotype) of another allele at the same locus | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/12%3A_Mendel's_Experiments_and_Heredity/12.01%3A_Mendels_Experiments_and_the_Laws_of_Probability/12.1D%3A_Garden_Pea_Characteristics_Revealed_the_Basics_o.txt |
Learning Objectives
• Calculate the probability of traits of pea plants using Mendelian crosses
Probability Basics
Probabilities are mathematical measures of likelihood. The empirical probability of an event is calculated by dividing the number of times the event occurs by the total number of opportunities for the event to occur. Empirical probabilities come from observations such as those of Mendel. An example of a genetic event is a round seed produced by a pea plant. Mendel demonstrated that the probability of the event “round seed” was guaranteed to occur in the F1 offspring of true-breeding parents, one of which has round seeds and one of which has wrinkled seeds. When the F1 plants were subsequently self-crossed, the probability of any given F2 offspring having round seeds was now three out of four. In other words, in a large population of F2 offspring chosen at random, 75 percent were expected to have round seeds, whereas 25 percent were expected to have wrinkled seeds. Using large numbers of crosses, Mendel was able to calculate probabilities and use these to predict the outcomes of other crosses.
The Product Rule
Mendel demonstrated that the pea-plant characteristics he studied were transmitted as discrete units from parent to offspring. Mendel also determined that different characteristics were transmitted independently of one another and could be considered in separate probability analyses. For instance, performing a cross between a plant with green, wrinkled seeds and a plant with yellow, round seeds produced offspring that had a 3:1 ratio of green:yellow seeds and a 3:1 ratio of round:wrinkled seeds. The characteristics of color and texture did not influence each other.
The product rule of probability can be applied to this phenomenon of the independent transmission of characteristics. It states that the probability of two independent events occurring together can be calculated by multiplying the individual probabilities of each event occurring alone. Imagine that you are rolling a six-sided die (D) and flipping a penny (P) at the same time. The die may roll any number from 1–6 (D#), whereas the penny may turn up heads (PH) or tails (PT). The outcome of rolling the die has no effect on the outcome of flipping the penny and vice versa. There are 12 possible outcomes, and each is expected to occur with equal probability: D1PH, D1PT, D2PH, D2PT, D3PH, D3PT, D4PH, D4PT, D5PH, D5PT, D6PH, D6PT.
Of the 12 possible outcomes, the die has a 2/12 (or 1/6) probability of rolling a two, and the penny has a 6/12 (or 1/2) probability of coming up heads. The probability that you will obtain the combined outcome 2 and heads is: (D2) x (PH) = (1/6) x (1/2) or 1/12. The word “and” is a signal to apply the product rule. Consider how the product rule is applied to a dihybrid: the probability of having both dominant traits in the F2 progeny is the product of the probabilities of having the dominant trait for each characteristic.
The Sum Rule
The sum rule is applied when considering two mutually-exclusive outcomes that can result from more than one pathway. It states that the probability of the occurrence of one event or the other, of two mutually-exclusive events, is the sum of their individual probabilities. The word “or” indicates that you should apply the sum rule. Let’s imagine you are flipping a penny (P) and a quarter (Q). What is the probability of one coin coming up heads and one coming up tails? This can be achieved by two cases: the penny is heads (PH) and the quarter is tails (QT), or the quarter is heads (QH) and the penny is tails (PT). Either case fulfills the outcome. We calculate the probability of obtaining one head and one tail as [(PH) × (QT)] + [(QH) × (PT)] = [(1/2) × (1/2)] + [(1/2) × (1/2)] = 1/2. You should also notice that we used the product rule to calculate the probability of PH and QT and also the probability of PT and QH, before we summed them. The sum rule can be applied to show the probability of having just one dominant trait in the F2 generation of a dihybrid cross.
To use probability laws in practice, it is necessary to work with large sample sizes because small sample sizes are prone to deviations caused by chance. The large quantities of pea plants that Mendel examined allowed him to calculate the probabilities of the traits appearing in his F2 generation. This discovery meant that when parental traits were known, the offspring’s traits could be predicted accurately even before fertilization.
Key Points
• The Product Rule is used to determine the outcome of an event with two independent events; the probability of the event is the product of the probabilities of each individual event.
• The Sum Rule is used to determine the outcome of an event with two mutually exclusive events from multiple pathways; the probability of the event is the sum of the probabilities of each individual event.
• The Product Rule of probability is used to determine the probability of having both dominant traits in the F2progeny; it is the product of the probabilities of having the dominant trait for each characteristic.
• The Sum Rule of probability is used to determine the probability of having one dominant trait in the F2 generation of a dihybrid cross; it is the sum of the probabilities of each individual with that trait.
Key Terms
• sum rule: the probability of the occurrence of one event or the other event, of two mutually exclusive events, is the sum of their individual probabilities
• product rule: the probability of two independent events occurring together can be calculated by multiplying the individual probabilities of each event occurring alone
• probability: a number, between 0 and 1, expressing the precise likelihood of an event happening
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• Punnett square mendel flowers. Provided by: Wikimedia. Located at: commons.wikimedia.org/wiki/Fi...el_flowers.svg. License: CC BY-SA: Attribution-ShareAlike | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/12%3A_Mendel's_Experiments_and_Heredity/12.01%3A_Mendels_Experiments_and_the_Laws_of_Probability/12.1E%3A_Rules_of_Probability_for_Mendelian_Inheritance.txt |
Learning Objectives
• Describe the structure of a gene and how offspring inherit genes from each parent
Pairs of Unit Factors, or Genes
Mendel proposed that paired unit factors of heredity were transmitted faithfully from generation to generation by the dissociation and reassociation of paired factors during gametogenesis and fertilization, respectively. After he crossed peas with contrasting traits and found that the recessive trait resurfaced in the F2 generation, Mendel deduced that hereditary factors must be inherited as discrete units. This finding contradicted the belief at that time that parental traits were blended in the offspring.
A gene is made up of short sections of DNA that are contained on a chromosome within the nucleus of a cell. Genes control the development and function of all organs and all working systems in the body. A gene has a certain influence on how the cell works; the same gene in many different cells determines a certain physical or biochemical feature of the whole body (e.g., eye color or reproductive functions). All human cells hold approximately 21,000 different genes.
Genetics is the science of the way traits are passed from parent to offspring. For all forms of life, continuity of the species depends upon the genetic code being passed from parent to offspring. Evolution by natural selection is dependent on traits being heritable. Genetics is very important in human physiology because all attributes of the human body are affected by a person’s genetic code. It can be as simple as eye color, height, or hair color. Or it can be as complex as how well your liver processes toxins, whether you will be prone to heart disease or breast cancer, and whether you will be color blind.
Genetic inheritance begins at the time of conception. You inherited 23 chromosomes from your mother and 23 from your father. Together they form 22 pairs of autosomal chromosomes and a pair of sex chromosomes (either XX if you are female, or XY if you are male). Homologous chromosomes have the same genes in the same positions, but may have different alleles (varieties) of those genes. There can be many alleles of a gene within a population, but an individual within that population only has two copies and can be homozygous (both copies the same) or heterozygous (the two copies are different) for any given gene.
Key Points
• A gene is a stretch of DNA that helps to control the development and function of all organs and working systems in the body.
• Genes are passed from parent to offspring; the combination of these genes affects all aspects of the human body, from eye and hair color to how well the liver can process toxins.
• A human will inherit 23 chromosomes from its mother and 23 from its father; together, these form 23 pairs of chromosomes that direct the inherited characteristics of the individual.
• If the two copies of a gene inherited from each parent are the same, that individual is said to be homozygous for the gene; if the two copies inherited from each parent are different, that individual is said to be heterozygous for the gene.
Key Terms
• gene: a unit of heredity; the functional units of chromosomes that determine specific characteristics by coding for specific proteins
• chromosome: a structure in the cell nucleus that contains DNA, histone protein, and other structural proteins
• genetics: the branch of biology that deals with the transmission and variation of inherited characteristics, in particular chromosomes and DNA | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/12%3A_Mendel's_Experiments_and_Heredity/12.02%3A__Patterns_of_Inheritance/12.2A%3A__Genes_as_the_Unit_of_Heredity.txt |
Learning Objectives
• Distinguish between the phenotype and the genotype of an organism
Phenotypes and Genotypes
The observable traits expressed by an organism are referred to as its phenotype. An organism’s underlying genetic makeup, consisting of both physically visible and non-expressed alleles, is called its genotype. Johann Gregor Mendel’s (1822–1884) hybridization experiments demonstrate the difference between phenotype and genotype.
Mendel crossed or mated two true-breeding (self-pollinating) garden peas, Pisum saivum, by manually transferring pollen from the anther of a mature pea plant of one variety to the stigma of a separate mature pea plant of the second variety. Plants used in first-generation crosses were called P0, or parental generation one, plants. Mendel collected the seeds belonging to the P0plants that resulted from each cross and grew them the following season. These offspring were called the F1, or the first filial (filial = offspring, daughter or son), generation. Once Mendel examined the characteristics in the F1 generation of plants, he allowed them to self-fertilize naturally. He then collected and grew the seeds from the F1 plants to produce the F2, or second filial, generation.
When true-breeding plants in which one parent had white flowers and one had violet flowers were cross-fertilized, all of the F1 hybrid offspring had violet flowers. That is, the hybrid offspring were phenotypically identical to the true-breeding parent with violet flowers. However, we know that the allele donated by the parent with white flowers was not simply lost because it reappeared in some of the F2 offspring. Therefore, the F1 plants must have been genotypically different from the parent with violet flowers.
In his 1865 publication, Mendel reported the results of his crosses involving seven different phenotypes, each with two contrasting traits. A trait is defined as a variation in the physical appearance of a heritable characteristic. The characteristics included plant height, seed texture, seed color, flower color, pea pod size, pea pod color, and flower position. To fully examine each characteristic, Mendel generated large numbers of F1 and F2 plants, reporting results from 19,959 F2 plants alone. His findings were consistent. First, Mendel confirmed that he had plants that bred true for white or violet flower color. Regardless of how many generations Mendel examined, all self-crossed offspring of parents with white flowers had white flowers, and all self-crossed offspring of parents with violet flowers had violet flowers. In addition, Mendel confirmed that, other than flower color, the pea plants were physically identical.
Key Points
• Mendel used pea plants with seven distinct traits or phenotypes to determine the pattern of inheritance and the underlying genotypes.
• Mendel found that crossing two purebred pea plants which expressed different traits resulted in an F1generation where all the pea plants expressed the same trait or phenotype.
• When Mendel allowed the F1 plants to self-fertilize, the F2 generation showed two different phenotypes, indicating that the F1 plants had different genotypes.
Key Terms
• phenotype: the appearance of an organism based on a multifactorial combination of genetic traits and environmental factors, especially used in pedigrees
• genotype: the combination of alleles, situated on corresponding chromosomes, that determines a specific trait of an individual, such as “Aa” or “aa” | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/12%3A_Mendel's_Experiments_and_Heredity/12.02%3A__Patterns_of_Inheritance/12.2B%3A_Phenotypes_and_Genotypes.txt |
Learning Objectives
• Describe the Punnett square approach to a monohybrid cross
Punnett Square Approach to a Monohybrid Cross
When fertilization occurs between two true-breeding parents that differ in only one characteristic, the process is called a monohybrid cross, and the resulting offspring are monohybrids. Mendel performed seven monohybrid crosses involving contrasting traits for each characteristic. On the basis of his results in F1 and F2 generations, Mendel postulated that each parent in the monohybrid cross contributed one of two paired unit factors to each offspring and that every possible combination of unit factors was equally likely.
To demonstrate a monohybrid cross, consider the case of true-breeding pea plants with yellow versus green pea seeds. The dominant seed color is yellow; therefore, the parental genotypes were YY ( homozygous dominant) for the plants with yellow seeds and yy (homozygous recessive ) for the plants with green seeds, respectively. A Punnett square, devised by the British geneticist Reginald Punnett, can be drawn that applies the rules of probability to predict the possible outcomes of a genetic cross or mating and their expected frequencies.To prepare a Punnett square, all possible combinations of the parental alleles are listed along the top (for one parent) and side (for the other parent) of a grid, representing their meiotic segregation into haploid gametes. Then the combinations of egg and sperm are made in the boxes in the table to show which alleles are combining. Each box then represents the diploid genotype of a zygote, or fertilized egg, that could result from this mating. Because each possibility is equally likely, genotypic ratios can be determined from a Punnett square. If the pattern of inheritance (dominant or recessive) is known, the phenotypic ratios can be inferred as well. For a monohybrid cross of two true-breeding parents, each parent contributes one type of allele. In this case, only one genotype is possible. All offspring are Yy and have yellow seeds.
A self-cross of one of the Yy heterozygous offspring can be represented in a 2 × 2 Punnett square because each parent can donate one of two different alleles. Therefore, the offspring can potentially have one of four allele combinations: YY, Yy, yY, or yy. Notice that there are two ways to obtain the Yy genotype: a Y from the egg and a y from the sperm, or a y from the egg and a Y from the sperm. Both of these possibilities must be counted. Recall that Mendel’s pea-plant characteristics behaved in the same way in reciprocal crosses. Therefore, the two possible heterozygous combinations produce offspring that are genotypically and phenotypically identical despite their dominant and recessive alleles deriving from different parents. They are grouped together. Because fertilization is a random event, we expect each combination to be equally likely and for the offspring to exhibit a ratio of YY:Yy:yy genotypes of 1:2:1. Furthermore, because the YY and Yy offspring have yellow seeds and are phenotypically identical, applying the sum rule of probability, we expect the offspring to exhibit a phenotypic ratio of 3 yellow:1 green. Indeed, working with large sample sizes, Mendel observed approximately this ratio in every F2 generation resulting from crosses for individual traits.
Beyond predicting the offspring of a cross between known homozygous or heterozygous parents, Mendel also developed a way to determine whether an organism that expressed a dominant trait was a heterozygote or a homozygote. Called the test cross, this technique is still used by plant and animal breeders. In a test cross, the dominant-expressing organism is crossed with an organism that is homozygous recessive for the same characteristic. If the dominant-expressing organism is a homozygote, then all F1 offspring will be heterozygotes expressing the dominant trait. Alternatively, if the dominant expressing organism is a heterozygote, the F1 offspring will exhibit a 1:1 ratio of heterozygotes and recessive homozygotes. The test cross further validates Mendel’s postulate that pairs of unit factors segregate equally.
Key Points
• Fertilization between two true-breeding parents that differ in only one characteristic is called a monohybrid cross.
• For a monohybrid cross of two true-breeding parents, each parent contributes one type of allele resulting in all of the offspring with the same genotype.
• A test cross is a way to determine whether an organism that expressed a dominant trait was a heterozygote or a homozygote.
Key Terms
• monohybrid: a hybrid between two species that only have a difference of one gene
• homozygous: of an organism in which both copies of a given gene have the same allele
• heterozygous: of an organism which has two different alleles of a given gene
• Punnett square: a graphical representation used to determine the probability of an offspring expressing a particular genotype | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/12%3A_Mendel's_Experiments_and_Heredity/12.02%3A__Patterns_of_Inheritance/12.2C%3A_The_Punnett_Square_Approach_for_a_Monohybrid_Cross.txt |
Learning Objectives
• Discuss incomplete dominance, codominance, and multiple alleles as alternatives to dominance and recessiveness
Alternatives to Dominance and Recessiveness
Mendel’s experiments with pea plants suggested that: (1) two “units” or alleles exist for every gene; (2) alleles maintain their integrity in each generation (no blending); and (3) in the presence of the dominant allele, the recessive allele is hidden and makes no contribution to the phenotype. Therefore, recessive alleles can be “carried” and not expressed by individuals. Such heterozygous individuals are sometimes referred to as “carriers.” Further genetic studies in other plants and animals have shown that much more complexity exists, but that the fundamental principles of Mendelian genetics still hold true.
Mendel’s results, that traits are inherited as dominant and recessive pairs, contradicted the view at that time that offspring exhibited a blend of their parents’ traits. However, the heterozygote phenotype occasionally does appear to be intermediate between the two parents. For example, in the snapdragon, Antirrhinum majus, a cross between a homozygous parent with white flowers (CWCW) and a homozygous parent with red flowers (CRCR) will produce offspring with pink flowers (CRCW). This pattern of inheritance is described as incomplete dominance, denoting the expression of two contrasting alleles such that the individual displays an intermediate phenotype. The allele for red flowers is incompletely dominant over the allele for white flowers. However, the results of a heterozygote self-cross can still be predicted, just as with Mendelian dominant and recessive crosses. In this case, the genotypic ratio would be 1 CRCR:2 CRCW:1 CWCW, and the phenotypic ratio would be 1:2:1 for red:pink:white.
A variation on incomplete dominance is codominance, in which both alleles for the same characteristic are simultaneously expressed in the heterozygote. An example of codominance is the MN blood groups of humans. The M and N alleles are expressed in the form of an M or N antigen present on the surface of red blood cells. Homozygotes (LMLMand LNLN) express either the M or the N allele, and heterozygotes (LMLN) express both alleles equally. In a self-cross between heterozygotes expressing a codominant trait, the three possible offspring genotypes are phenotypically distinct. However, the 1:2:1 genotypic ratio characteristic of a Mendelian monohybrid cross still applies.
Mendel implied that only two alleles, one dominant and one recessive, could exist for a given gene. We now know that this is an oversimplification. Although individual humans (and all diploid organisms) can only have two alleles for a given gene, multiple alleles may exist at the population level such that many combinations of two alleles are observed. Note that when many alleles exist for the same gene, the convention is to denote the most common phenotype or genotype among wild animals as the wild type (often abbreviated “+”); this is considered the standard or norm. All other phenotypes or genotypes are considered variants of this standard, meaning that they deviate from the wild type. The variant may be recessive or dominant to the wild-type allele. An example of multiple alleles is coat color in rabbits. Here, four alleles exist for the c gene. The wild-type version, C+C+, is expressed as brown fur. The chinchilla phenotype, cchcch, is expressed as black-tipped white fur. The Himalayan phenotype, chch, has black fur on the extremities and white fur elsewhere. Finally, the albino, or “colorless” phenotype, cc, is expressed as white fur. In cases of multiple alleles, dominance hierarchies can exist. In this case, the wild-type allele is dominant over all the others, chinchilla is incompletely dominant over Himalayan and albino, and Himalayan is dominant over albino. This hierarchy, or allelic series, was revealed by observing the phenotypes of each possible heterozygote offspring.
The complete dominance of a wild-type phenotype over all other mutants often occurs as an effect of “dosage” of a specific gene product, such that the wild-type allele supplies the correct amount of gene product whereas the mutant alleles cannot. For the allelic series in rabbits, the wild-type allele may supply a given dosage of fur pigment, whereas the mutants supply a lesser dosage or none at all. Alternatively, one mutant allele can be dominant over all other phenotypes, including the wild type. This may occur when the mutant allele somehow interferes with the genetic message so that even a heterozygote with one wild-type allele copy expresses the mutant phenotype. One way in which the mutant allele can interfere is by enhancing the function of the wild-type gene product or changing its distribution in the body. One example of this is the Antennapedia mutation in Drosophila. In this case, the mutant allele expands the distribution of the gene product; as a result, the Antennapedia heterozygote develops legs on its head where its antennae should be.
Key Points
• Incomplete dominance is the expression of two contrasting alleles such that the individual displays an intermediate phenotype.
• Codominance is a variation on incomplete dominance in which both alleles for the same characteristic are simultaneously expressed in the heterozygote.
• Diploid organisms can only have two alleles for a given gene; however, multiple alleles may exist at the population level such that many combinations of two alleles are observed.
• The complete dominance of a wild-type phenotype over all other mutants often occurs as an effect of “dosage” of a specific gene product: the wild-type allele supplies the correct amount of gene product whereas the mutant alleles cannot.
• One mutant allele can also be dominant over all other phenotypes, including the wild type.
Key Terms
• allele: one of a number of alternative forms of the same gene occupying a given position on a chromosome
• incomplete dominance: a condition in which the phenotype of the heterozygous genotype is distinct from and often intermediate to the phenotypes of the homozygous genotypes
• codominance: a condition in which both alleles of a gene pair in a heterozygote are fully expressed, with neither one being dominant or recessive to the other | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/12%3A_Mendel's_Experiments_and_Heredity/12.02%3A__Patterns_of_Inheritance/12.2D%3A_Alternatives_to_Dominance_and_Recessiveness.txt |
Learning Objectives
• Distinguish between sex-linked traits and other forms of inheritance
Sex Determination
In humans, as well as in many other animals and some plants, the sex of the individual is determined by sex chromosomes. However, there are other sex determination systems in nature. For example, temperature-dependent sex determination is relatively common,
and there are many other types of environmental sex determination. Some species, such as some snails, practice sex change adults start out male, then become female. In tropical clown fish, the dominant individual in a group becomes female while the others are male.
The sex chromosomes are one pair of non-homologous chromosomes. Until now, we have only considered inheritance patterns among non-sex chromosomes, or autosomes. In addition to 22 homologous pairs of autosomes, human females have a homologous pair of X chromosomes, whereas human males have an XY chromosome pair. Although the Y chromosome contains a small region of similarity to the X chromosome so that they can pair during meiosis, the Y chromosome is much shorter and contains many fewer genes. When a gene being examined is present on the X chromosome, but not on the Y chromosome, it is said to be X-linked.
X-Linked Traits
Insects also follow an XY sex-determination pattern and like humans, Drosophila males have an XY chromosome pair and females are XX. Eye color in Drosophila was one of the first X-linked traits to be identified, and Thomas Hunt Morgan mapped this trait to the X chromosome in 1910.
In fruit flies, the wild-type eye color is red (XW) and is dominant to white eye color (Xw). Because this eye-color gene is located on the X chromosome only, reciprocal crosses do not produce the same offspring ratios. Males are said to be hemizygous, because they have only one allele for any X-linked characteristic. Hemizygosity makes the descriptions of dominance and recessiveness irrelevant for XY males because each male only has one copy of the gene. Drosophila males lack a second allele copy on the Y chromosome; their genotype can only be XWY or XwY. In contrast, females have two allele copies of this gene and can be XWXW, XWXw, or XwXw.
X-Linked Crosses
In an X-linked cross, the genotypes of F1 and F2 offspring depend on whether the recessive trait was expressed by the male or the female in the P1 generation. With regard to Drosophila eye color, when the P1 male expresses the white-eye phenotype and the female is homozygous red-eyed, all members of the F1 generation exhibit red eyes. The F1 females are heterozygous (XWXw), and the males are all XWY, having received their X chromosome from the homozygous dominant P1 female and their Y chromosome from the P1 male.
A subsequent cross between the XWXw female and the XWY male would produce only red-eyed females (with XWXW or XWXwgenotypes) and both red- and white-eyed males (with XWY or XwY genotypes). Now, consider a cross between a homozygous white-eyed female and a male with red eyes. The F1 generation would exhibit only heterozygous red-eyed females (XWXw) and only white-eyed males (XwY). Half of the F2 females would be red-eyed (XWXw) and half would be white-eyed (XwXw). Similarly, half of the F2 males would be red-eyed (XWY) and half would be white-eyed (XwY).
X-Linked Recessive Disorders in Humans
Sex-linkage studies provided the fundamentals for understanding X-linked recessive disorders in humans, which include red-green color blindness and Types A and B hemophilia. Because human males need to inherit only one recessive mutant X allele to be affected, X-linked disorders are disproportionately observed in males. Females must inherit recessive X-linked alleles from both of their parents in order to express the trait.
Recessive Carriers
When they inherit one recessive X-linked mutant allele and one dominant X-linked wild-type allele, they are carriers of the trait and are typically unaffected. Carrier females can manifest mild forms of the trait due to the inactivation of the dominant allele located on one of the X chromosomes. However, female carriers can contribute the trait to their sons, resulting in the son exhibiting the trait, or they can contribute the recessive allele to their daughters, resulting in the daughters being carriers of the trait. Although some Y-linked recessive disorders exist, typically they are associated with infertility in males and are, therefore, not transmitted to subsequent generations.
Key Points
• In mammals, females have a homologous pair of X chromosomes, whereas males have an XY chromosome pair.
• The Y chromosome contains a small region of similarity to the X chromosome so that they can pair during meiosis, but the Y is much shorter and contains fewer genes.
• Males are said to be hemizygous because they have only one allele for any X-linked characteristic; males will exhibit the trait of any gene on the X-chromosome regardless of dominance and recessiveness.
• Most sex-linked traits are actually X-linked, such as eye color in Drosophila or color blindness in humans.
Key Terms
• hemizygous: Having some single copies of genes in an otherwise diploid cell or organism.
• X-linked: Associated with the X chromosome.
• carrier: A person or animal that transmits a disease to others without itself contracting the disease.
• sex chromosomes: A chromosome involved with determining the sex of an organism, typically one of two kinds. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/12%3A_Mendel's_Experiments_and_Heredity/12.02%3A__Patterns_of_Inheritance/12.2E%3A_Sex-Linked_Traits.txt |
Learning Objectives
• Describe recessive and dominant lethal inheritance patterns
Lethal Inheritance Patterns
A large proportion of genes in an individual’s genome are essential for survival. Occasionally, a nonfunctional allele for an essential gene can arise by mutation and be transmitted in a population as long as individuals with this allele also have a wild-type, functional copy. The wild-type allele functions at a capacity sufficient to sustain life and is, therefore, considered to be dominant over the nonfunctional allele. However, consider two heterozygous parents that have a genotype of wild-type/nonfunctional mutant for a hypothetical essential gene. In one quarter of their offspring, we would expect to observe individuals that are homozygous recessive for the nonfunctional allele. Because the gene is essential, these individuals might fail to develop past fertilization, die in utero, or die later in life, depending on what life stage requires this gene. An inheritance pattern in which an allele is only lethal in the homozygous form and in which the heterozygote may be normal or have some altered non-lethal phenotype is referred to as recessive lethal.
For crosses between heterozygous individuals with a recessive lethal allele that causes death before birth when homozygous, only wild-type homozygotes and heterozygotes would be observed. The genotypic ratio would therefore be 2:1. In other instances, the recessive lethal allele might also exhibit a dominant (but not lethal) phenotype in the heterozygote. For instance, the recessive lethal Curly allele in Drosophila affects wing shape in the heterozygote form, but is lethal in the homozygote.
Dominant Lethal Alleles
A single copy of the wild-type allele is not always sufficient for normal functioning or even survival. The dominant lethal inheritance pattern is one in which an allele is lethal both in the homozygote and the heterozygote; this allele can only be transmitted if the lethality phenotype occurs after reproductive age. Individuals with mutations that result in dominant lethal alleles fail to survive even in the heterozygote form. Dominant lethal alleles are very rare because, as you might expect, the allele only lasts one generation and is not transmitted. However, just as the recessive lethal allele might not immediately manifest the phenotype of death, dominant lethal alleles also might not be expressed until adulthood. Once the individual reaches reproductive age, the allele may be unknowingly passed on, resulting in a delayed death in both generations. An example of this in humans is Huntington’s disease in which the nervous system gradually wastes away. People who are heterozygous for the dominant Huntington allele (Hh) will inevitably develop the fatal disease. However, the onset of Huntington’s disease may not occur until age 40, at which point the afflicted persons may have already passed the allele to 50 percent of their offspring.
Key Points
• An inheritance pattern in which an allele is only lethal in the homozygous form and in which the heterozygote may be normal or have some altered non-lethal phenotype is referred to as recessive lethal.
• The dominant lethal inheritance pattern is one in which an allele is lethal both in the homozygote and the heterozygote; this allele can only be transmitted if the lethality phenotype occurs after reproductive age.
• Dominant lethal alleles are very rare because the allele only lasts one generation and is, therefore, not usually transmitted.
• In the case where dominant lethal alleles might not be expressed until adulthood, the allele may be unknowingly passed on, resulting in a delayed death in both generations.
Key Terms
• mutation: any heritable change of the base-pair sequence of genetic material
• recessive lethal: an inheritance pattern in which an allele is only lethal in the homozygous form and in which the heterozygote may be normal or have some altered non-lethal phenotype
• dominant lethal: an inheritance pattern is one in which an allele is lethal both in the homozygote and the heterozygote; this allele can only be transmitted if the lethality phenotype occurs after reproductive age | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/12%3A_Mendel's_Experiments_and_Heredity/12.02%3A__Patterns_of_Inheritance/12.2F%3A_Lethal_Inheritance_Patterns.txt |
Learning Objectives
• Discuss the methods Mendel utilized in his research that led to his success in understanding the process of inheritance
Introduction
Mendelian inheritance (or Mendelian genetics or Mendelism) is a set of primary tenets relating to the transmission of hereditary characteristics from parent organisms to their children; it underlies much of genetics. The tenets were initially derived from the work of Gregor Mendel published in 1865 and 1866, which was “re-discovered” in 1900; they were initially very controversial, but they soon became the core of classical genetics.
The laws of inheritance were derived by Gregor Mendel, a 19th century monk conducting hybridization experiments in garden peas (Pisum sativum). Between 1856 and 1863, he cultivated and tested some 28,000 pea plants. From these experiments, he deduced two generalizations that later became known as Mendel’s Laws of Heredity or Mendelian inheritance. He described these laws in a two part paper, “Experiments on Plant Hybridization”, which was published in 1866.
Mendel’s Laws
Mendel discovered that by crossing true-breeding white flower and true-breeding purple flower plants, the result was a hybrid offspring. Rather than being a mix of the two colors, the offspring was purple flowered. He then conceived the idea of heredity units, which he called “factors”, one of which is a recessive characteristic and the other dominant. Mendel said that factors, later called genes, normally occur in pairs in ordinary body cells, yet segregate during the formation of sex cells. Each member of the pair becomes part of the separate sex cell. The dominant gene, such as the purple flower in Mendel’s plants, will hide the recessive gene, the white flower. After Mendel self-fertilized the F1 generation and obtained an F2 generation with a 3:1 ratio, he correctly theorized that genes can be paired in three different ways for each trait: AA, aa, and Aa. The capital A represents the dominant factor while the lowercase a represents the recessive.
Mendel stated that each individual has two alleles for each trait, one from each parent. Thus, he formed the “first rule”, the Law of Segregation, which states individuals possess two alleles and a parent passes only one allele to his/her offspring. One allele is given by the female parent and the other is given by the male parent. The two factors may or may not contain the same information. If the two alleles are identical, the individual is called homozygous for the trait. If the two alleles are different, the individual is called heterozygous. The presence of an allele does not promise that the trait will be expressed in the individual that possesses it. In heterozygous individuals, the only allele that is expressed is the dominant. The recessive allele is present, but its expression is hidden. The genotype of an individual is made up of the many alleles it possesses. An individual’s physical appearance, or phenotype, is determined by its alleles as well as by its environment.
Mendel also analyzed the pattern of inheritance of seven pairs of contrasting traits in the domestic pea plant. He did this by cross-breeding dihybrids; that is, plants that were heterozygous for the alleles controlling two different traits. Mendel then crossed these dihybrids. If it is inevitable that round seeds must always be yellow and wrinkled seeds must be green, then he would have expected that this would produce a typical monohybrid cross: 75 percent round-yellow; 25 percent wrinkled-green. But, in fact, his mating generated seeds that showed all possible combinations of the color and texture traits. He found 9/16 of the offspring were round-yellow, 3/16 were round-green, 3/16 were wrinkled-yellow, and 1/16 were wrinkled-green. Finding in every case that each of his seven traits was inherited independently of the others, he formed his “second rule”, the Law of Independent Assortment, which states the inheritance of one pair of factors (genes) is independent of the inheritance of the other pair. Today we know that this rule holds only if the genes are on separate chromosomes
Key Points
• By crossing purple and white pea plants, Mendel found the offspring were purple rather than mixed, indicating one color was dominant over the other.
• Mendel’s Law of Segregation states individuals possess two alleles and a parent passes only one allele to his/her offspring.
• Mendel’s Law of Independent Assortment states the inheritance of one pair of factors ( genes ) is independent of the inheritance of the other pair.
• If the two alleles are identical, the individual is called homozygous for the trait; if the two alleles are different, the individual is called heterozygous.
• Mendel cross-bred dihybrids and found that traits were inherited independently of each other.
Key Terms
• homozygous: of an organism in which both copies of a given gene have the same allele
• heterozygous: of an organism which has two different alleles of a given gene
• allele: one of a number of alternative forms of the same gene occupying a given position on a chromosome | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/12%3A_Mendel's_Experiments_and_Heredity/12.03%3A_Laws_of_Inheritance/12.3A%3A_Mendels_Laws_of_Heredity.txt |
Learning Objectives
• Explain the concept of dominance versus recessiveness
Alleles Can Be Dominant or Recessive
Most familiar animals and some plants have paired chromosomes and are described as diploid. They have two versions of each chromosome: one contributed by the female parent in her ovum and one by the male parent in his sperm. These are joined at fertilization. The ovum and sperm cells (the gametes) have only one copy of each chromosome and are described as haploid.
Mendel’s law of dominance states that in a heterozygote, one trait will conceal the presence of another trait for the same characteristic. Rather than both alleles contributing to a phenotype, the dominant allele will be expressed exclusively. The recessive allele will remain “latent,” but will be transmitted to offspring by the same manner in which the dominant allele is transmitted. The recessive trait will only be expressed by offspring that have two copies of this allele; these offspring will breed true when self-crossed.
By definition, the terms dominant and recessive refer to the genotypic interaction of alleles in producing the phenotype of the heterozygote. The key concept is genetic: which of the two alleles present in the heterozygote is expressed, such that the organism is phenotypically identical to one of the two homozygotes. It is sometimes convenient to talk about the trait corresponding to the dominant allele as the dominant trait and the trait corresponding to the hidden allele as the recessive trait. However, this can easily lead to confusion in understanding the concept as phenotypic. For example, to say that “green peas” dominate “yellow peas” confuses inherited genotypes and expressed phenotypes. This will subsequently confuse discussion of the molecular basis of the phenotypic difference. Dominance is not inherent. One allele can be dominant to a second allele, recessive to a third allele, and codominant to a fourth. If a genetic trait is recessive, a person needs to inherit two copies of the gene for the trait to be expressed. Thus, both parents have to be carriers of a recessive trait in order for a child to express that trait.
Since Mendel’s experiments with pea plants, other researchers have found that the law of dominance does not always hold true. Instead, several different patterns of inheritance have been found to exist.
Key Points
• Dominant alleles are expressed exclusively in a heterozygote, while recessive traits are expressed only if the organism is homozygous for the recessive allele.
• A single allele may be dominant over one allele, but recessive to another.
• Not all traits are controlled by simple dominance as a form of inheritance; more complex forms of inheritance have been found to exist.
Key Terms
• dominant: a relationship between alleles of a gene, in which one allele masks the expression (phenotype) of another allele at the same locus
• recessive: able to be covered up by a dominant trait
12.3C: Mendels Law of Segregation
Learning Objectives
• Apply the law of segregation to determine the chances of a particular genotype arising from a genetic cross
Equal Segregation of Alleles
Observing that true-breeding pea plants with contrasting traits gave rise to F1 generations that all expressed the dominant trait and F2 generations that expressed the dominant and recessive traits in a 3:1 ratio, Mendel proposed the law of segregation. The law of segregation states that each individual that is a diploid has a pair of alleles (copy) for a particular trait. Each parent passes an allele at random to their offspring resulting in a diploid organism. The allele that contains the dominant trait determines the phenotype of the offspring. In essence, the law states that copies of genes separate or segregate so that each gamete receives only one allele.
For the F2 generation of a monohybrid cross, the following three possible combinations of genotypes could result: homozygous dominant, heterozygous, or homozygous recessive. Because heterozygotes could arise from two different pathways (receiving one dominant and one recessive allele from either parent), and because heterozygotes and homozygous dominant individuals are phenotypically identical, the law supports Mendel’s observed 3:1 phenotypic ratio. The equal segregation of alleles is the reason we can apply the Punnett square to accurately predict the offspring of parents with known genotypes.
The physical basis of Mendel’s law of segregation is the first division of meiosis in which the homologous chromosomes with their different versions of each gene are segregated into daughter nuclei. The behavior of homologous chromosomes during meiosis can account for the segregation of the alleles at each genetic locus to different gametes. As chromosomes separate into different gametes during meiosis, the two different alleles for a particular gene also segregate so that each gamete acquires one of the two alleles. In Mendel’s experiments, the segregation and the independent assortment during meiosis in the F1 generation give rise to the F2 phenotypic ratios observed by Mendel. The role of the meiotic segregation of chromosomes in sexual reproduction was not understood by the scientific community during Mendel’s lifetime.
Key Points
• Each gamete acquires one of the two alleles as chromosomes separate into different gametes during meiosis.
• Heterozygotes, which posess one dominant and one recessive allele, can receive each allele from either parent and will look identical to homozygous dominant individuals; the Law of Segregation supports Mendel’s observed 3:1 phenotypic ratio.
• Mendel proposed the Law of Segregation after observing that pea plants with two different traits produced offspring that all expressed the dominant trait, but the following generation expressed the dominant and recessive traits in a 3:1 ratio.
Key Terms
• law of segregation: a diploid individual possesses a pair of alleles for any particular trait and each parent passes one of these randomly to its offspring | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/12%3A_Mendel's_Experiments_and_Heredity/12.03%3A_Laws_of_Inheritance/12.3B%3A_Mendels_Law_of_Dominance.txt |
Learning Objectives
• Use the probability or forked line method to calculate the chance of any particular genotype arising from a genetic cross
Independent Assortment
Mendel’s law of independent assortment states that genes do not influence each other with regard to the sorting of alleles into gametes: every possible combination of alleles for every gene is equally likely to occur. The independent assortment of genes can be illustrated by the dihybrid cross: a cross between two true-breeding parents that express different traits for two characteristics. Consider the characteristics of seed color and seed texture for two pea plants: one that has green, wrinkled seeds (yyrr) and another that has yellow, round seeds (YYRR). Because each parent is homozygous, the law of segregation indicates that the gametes for the green/wrinkled plant all are yr, while the gametes for the yellow/round plant are all YR. Therefore, the F1 generation of offspring all are YyRr.
For the F2 generation, the law of segregation requires that each gamete receive either an R allele or an r allele along with either a Y allele or a y allele. The law of independent assortment states that a gamete into which an r allele sorted would be equally likely to contain either a Y allele or a y allele. Thus, there are four equally likely gametes that can be formed when the YyRr heterozygote is self-crossed as follows: YR, Yr, yR, and yr. Arranging these gametes along the top and left of a 4 × 4 Punnett square gives us 16 equally likely genotypic combinations. From these genotypes, we infer a phenotypic ratio of 9 round/yellow:3 round/green:3 wrinkled/yellow:1 wrinkled/green. These are the offspring ratios we would expect, assuming we performed the crosses with a large enough sample size.
Because of independent assortment and dominance, the 9:3:3:1 dihybrid phenotypic ratio can be collapsed into two 3:1 ratios, characteristic of any monohybrid cross that follows a dominant and recessive pattern. Ignoring seed color and considering only seed texture in the above dihybrid cross, we would expect that three-quarters of the F2 generation offspring would be round and one-quarter would be wrinkled. Similarly, isolating only seed color, we would assume that three-quarters of the F2offspring would be yellow and one-quarter would be green. The sorting of alleles for texture and color are independent events, so we can apply the product rule. Therefore, the proportion of round and yellow F2 offspring is expected to be (3/4) × (3/4) = 9/16, and the proportion of wrinkled and green offspring is expected to be (1/4) × (1/4) = 1/16. These proportions are identical to those obtained using a Punnett square. Round/green and wrinkled/yellow offspring can also be calculated using the product rule as each of these genotypes includes one dominant and one recessive phenotype. Therefore, the proportion of each is calculated as (3/4) × (1/4) = 3/16.
Forked-Line Method
When more than two genes are being considered, the Punnett-square method becomes unwieldy. For instance, examining a cross involving four genes would require a 16 × 16 grid containing 256 boxes. It would be extremely cumbersome to manually enter each genotype. For more complex crosses, the forked-line and probability methods are preferred.
To prepare a forked-line diagram for a cross between F1 heterozygotes resulting from a cross between AABBCC and aabbcc parents, we first create rows equal to the number of genes being considered and then segregate the alleles in each row on forked lines according to the probabilities for individual monohybrid crosses. We then multiply the values along each forked path to obtain the F2 offspring probabilities. Note that this process is a diagrammatic version of the product rule. The values along each forked pathway can be multiplied because each gene assorts independently. For a trihybrid cross, the F2phenotypic ratio is 27:9:9:9:3:3:3:1.
Probability Method
While the forked-line method is a diagrammatic approach to keeping track of probabilities in a cross, the probability method gives the proportions of offspring expected to exhibit each phenotype (or genotype) without the added visual assistance.
To fully demonstrate the power of the probability method, however, we can consider specific genetic calculations. For instance, for a tetrahybrid cross between individuals that are heterozygotes for all four genes, and in which all four genes are sorting independently in a dominant and recessive pattern, what proportion of the offspring will be expected to be homozygous recessive for all four alleles? Rather than writing out every possible genotype, we can use the probability method. We know that for each gene the fraction of homozygous recessive offspring will be 1/4. Therefore, multiplying this fraction for each of the four genes, (1/4) × (1/4) × (1/4) × (1/4), we determine that 1/256 of the offspring will be quadruply homozygous recessive.
Key Points
• Mendel’s law of independent assortment states that genes do not influence each other with regard to the sorting of alleles into gametes; every possible combination of alleles for every gene is equally likely to occur.
• The calculation of any particular genotypic combination of more than one gene is, therefore, the probability of the desired genotype at the first locus multiplied by the probability of the desired genotype at the other loci.
• The forked line method can be used to calculate the chances of all possible genotypic combinations from a cross, while the probability method can be used to calculate the chance of any one particular genotype that might result from that cross.
Key Terms
• independent assortment: separate genes for separate traits are passed independently of one another from parents to offspring | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/12%3A_Mendel's_Experiments_and_Heredity/12.03%3A_Laws_of_Inheritance/12.3D%3A_Mendels_Law_of_Independent_Assortment.txt |
Learning Objectives
• Describe how recombination can separate linked genes
Linked Genes Violate the Law of Independent Assortment
Although all of Mendel’s pea characteristics behaved according to the law of independent assortment, we now know that some allele combinations are not inherited independently of each other. Genes that are located on separate non-homologous chromosomes will always sort independently. However, each chromosome contains hundreds or thousands of genes organized linearly on chromosomes like beads on a string. The segregation of alleles into gametes can be influenced by linkage, in which genes that are located physically close to each other on the same chromosome are more likely to be inherited as a pair. However, because of the process of recombination, or “crossover,” it is possible for two genes on the same chromosome to behave independently, or as if they are not linked. To understand this, let’s consider the biological basis of gene linkage and recombination.
Homologous chromosomes possess the same genes in the same linear order. The alleles may differ on homologous chromosome pairs, but the genes to which they correspond do not. In preparation for the first division of meiosis, homologous chromosomes replicate and synapse. Like genes on the homologs align with each other. At this stage, segments of homologous chromosomes exchange linear segments of genetic material. This process is called recombination, or crossover, and it is a common genetic process. Because the genes are aligned during recombination, the gene order is not altered. Instead, the result of recombination is that maternal and paternal alleles are combined onto the same chromosome. Across a given chromosome, several recombination events may occur, causing extensive shuffling of alleles.
When two genes are located in close proximity on the same chromosome, they are considered linked, and their alleles tend to be transmitted through meiosis together. To exemplify this, imagine a dihybrid cross involving flower color and plant height in which the genes are next to each other on the chromosome. If one homologous chromosome has alleles for tall plants and red flowers, and the other chromosome has genes for short plants and yellow flowers, then when the gametes are formed, the tall and red alleles will go together into a gamete and the short and yellow alleles will go into other gametes. These are called the parental genotypes because they have been inherited intact from the parents of the individual producing gametes. But unlike if the genes were on different chromosomes, there will be no gametes with tall and yellow alleles and no gametes with short and red alleles. If you create the Punnett square with these gametes, you will see that the classical Mendelian prediction of a 9:3:3:1 outcome of a dihybrid cross would not apply. As the distance between two genes increases, the probability of one or more crossovers between them increases, and the genes behave more like they are on separate chromosomes. Geneticists have used the proportion of recombinant gametes (the ones not like the parents) as a measure of how far apart genes are on a chromosome. Using this information, they have constructed elaborate maps of genes on chromosomes for well-studied organisms, including humans.
Mendel’s seminal publication makes no mention of linkage, and many researchers have questioned whether he encountered linkage, but chose not to publish those crosses out of concern that they would invalidate his independent assortment postulate. The garden pea has seven chromosomes and some have suggested that his choice of seven characteristics was not a coincidence. However, even if the genes he examined were not located on separate chromosomes, it is possible that he simply did not observe linkage because of the extensive shuffling effects of recombination.
Key Points
• Two genes close together on the same chromosome tend to be inherited together and are said to be linked.
• Linked genes can be separated by recombination in which homologous chromosomes exchange genetic information during meiosis; this results in parental, or nonrecombinant genotypes, as well as a smaller proportion of recombinant genotypes.
• Geneticists can use the amount of recombination between genes to estimate the distance between them on a chromosome.
Key Terms
• linkage: the property of genes of being inherited together
• recombination: the formation of genetic combinations in offspring that are not present in the parents | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/12%3A_Mendel's_Experiments_and_Heredity/12.03%3A_Laws_of_Inheritance/12.3E%3A_Genetic_Linkage_and_Violation_of_the_Law_of_Independent_Assortment.txt |
Learning Objectives
• Explain the phenotypic outcomes of epistatic effects between genes
Epistasis
Mendel’s studies in pea plants implied that the sum of an individual’s phenotype was controlled by genes (or as he called them, unit factors): every characteristic was distinctly and completely controlled by a single gene. In fact, single observable characteristics are almost always under the influence of multiple genes (each with two or more alleles) acting in unison. For example, at least eight genes contribute to eye color in humans.
In some cases, several genes can contribute to aspects of a common phenotype without their gene products ever directly interacting. In the case of organ development, for instance, genes may be expressed sequentially, with each gene adding to the complexity and specificity of the organ. Genes may function in complementary or synergistic fashions: two or more genes need to be expressed simultaneously to affect a phenotype. Genes may also oppose each other with one gene modifying the expression of another.
In epistasis, the interaction between genes is antagonistic: one gene masks or interferes with the expression of another. “Epistasis” is a word composed of Greek roots that mean “standing upon.” The alleles that are being masked or silenced are said to be hypostatic to the epistatic alleles that are doing the masking. Often the biochemical basis of epistasis is a gene pathway in which the expression of one gene is dependent on the function of a gene that precedes or follows it in the pathway.
An example of epistasis is pigmentation in mice. The wild-type coat color, agouti (AA), is dominant to solid-colored fur (aa). However, a separate gene (C) is necessary for pigment production. A mouse with a recessive c allele at this locus is unable to produce pigment and is albino regardless of the allele present at locus A. Therefore, the genotypes AAcc, Aacc, and aacc all produce the same albino phenotype. A cross between heterozygotes for both genes (AaCc x AaCc) would generate offspring with a phenotypic ratio of 9 agouti:3 solid color:4 albino. In this case, the C gene is epistatic to the A gene.
Epistasis can also occur when a dominant allele masks expression at a separate gene. Fruit color in summer squash is expressed in this way. Homozygous recessive expression of the W gene (ww) coupled with homozygous dominant or heterozygous expression of the Y gene (YY or Yy) generates yellow fruit, while the wwyy genotype produces green fruit. However, if a dominant copy of the W gene is present in the homozygous or heterozygous form, the summer squash will produce white fruit regardless of the Y alleles. A cross between white heterozygotes for both genes (WwYy × WwYy) would produce offspring with a phenotypic ratio of 12 white:3 yellow:1 green.
Finally, epistasis can be reciprocal: either gene, when present in the dominant (or recessive) form, expresses the same phenotype. In the shepherd’s purse plant (Capsella bursa-pastoris), the characteristic of seed shape is controlled by two genes in a dominant epistatic relationship. When the genes A and B are both homozygous recessive (aabb), the seeds are ovoid. If the dominant allele for either of these genes is present, the result is triangular seeds. That is, every possible genotype other than aabb results in triangular seeds; a cross between heterozygotes for both genes (AaBb x AaBb) would yield offspring with a phenotypic ratio of 15 triangular:1 ovoid.
Keep in mind that any single characteristic that results in a phenotypic ratio that totals 16 is typical of a two-gene interaction. Recall the phenotypic inheritance pattern for Mendel’s dihybrid cross, which considered two non-interacting genes: 9:3:3:1. Similarly, we would expect interacting gene pairs to also exhibit ratios expressed as 16 parts. Note that we are assuming the interacting genes are not linked; they are still assorting independently into gametes.
Key Points
• In many cases, several genes may contribute to a particular phenotype; when the actions of one gene masks the effects of another, this gene is said to be epistatic to the second.
• Epistasis can occur when a recessive genotype masks the actions of another gene, or when a dominant allele masks the effects of another gene.
• Epistasis can be reciprocal: either gene, when present in the dominant (or recessive) form, expresses the same phenotype.
• Any single characteristic that results in a phenotypic ratio that totals 16 (such as 12:3:1, 9:3:4, or others) is typical of a two-gene interaction.
Key Terms
• epistasis: the modification of the expression of a gene by another unrelated one | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/12%3A_Mendel's_Experiments_and_Heredity/12.03%3A_Laws_of_Inheritance/12.3F%3A_Epistasis.txt |
Learning Objectives
• List the reasons that fruit flies are excellent model organisms for genetic research
Chromosomal Theory of Inheritance
The speculation that chromosomes might be the key to understanding heredity led several scientists to examine Mendel’s publications and re-evaluate his model in terms of the behavior of chromosomes during mitosis and meiosis. In 1902, Theodor Boveri observed that proper embryonic development of sea urchins does not occur unless chromosomes are present. That same year, Walter Sutton observed the separation of chromosomes into daughter cells during meiosis. Together, these observations led to the development of the Chromosomal Theory of Inheritance, which identified chromosomes as the genetic material responsible for Mendelian inheritance.
The Chromosomal Theory of Inheritance was consistent with Mendel’s laws and was supported by the following observations:
• During meiosis, homologous chromosome pairs migrate as discrete structures that are independent of other chromosome pairs.
• The sorting of chromosomes from each homologous pair into pre-gametes appears to be random.
• Each parent synthesizes gametes that contain only half of their chromosomal complement.
• Even though male and female gametes (sperm and egg) differ in size and morphology, they have the same number of chromosomes, suggesting equal genetic contributions from each parent.
• The gametic chromosomes combine during fertilization to produce offspring with the same chromosome number as their parents.
Despite compelling correlations between the behavior of chromosomes during meiosis and Mendel’s abstract laws, the Chromosomal Theory of Inheritance was proposed long before there was any direct evidence that traits were carried on chromosomes. Critics pointed out that individuals had far more independently segregating traits than they had chromosomes. It was only after several years of carrying out crosses with the fruit fly, Drosophila melanogaster, that Thomas Hunt Morgan provided experimental evidence to support the Chromosomal Theory of Inheritance.
In 1910, Thomas Hunt Morgan started his work with Drosophila melanogaster, a fruit fly. He chose fruit flies because they can be cultured easily, are present in large numbers, have a short generation time, and have only four pair of chromosomes that can be easily identified under the microscope. They have three pair of autosomes and a pair of sex chromosomes. At that time, he already knew that X and Y have to do with gender. He used normal flies with red eyes and mutated flies with white eyes and cross bred them. In flies, the wild type eye color is red (XW) and is dominant to white eye color (Xw). He was able to conclude that the gene for eye color was on the X chromosome. This trait was thus determined to be X-linked and was the first X-linked trait to be identified. Males are said to be hemizygous, in that they have only one allele for any X-linked characteristic.
Key Points
• Homologous chromosome pairs are independent of other chromosome pairs.
• Chromosomes from each homologous pair are sorted randomly into pre- gametes.
• Parents synthesize gametes that contain only half of their chromosomes; eggs and sperm have the same number of chromosomes.
• Gametic chromosomes combine during fertilization to produce offspring with the same chromosome number as their parents.
• Eye color in fruit flies was the first X-linked trait to be discovered; thus, Morgan’s experiments with fruit flies solidified the Chromosomal Theory of Inheritance.
Key Terms
• autosome: any chromosome other than sex chromosomes
• hemizygous: having some single copies of genes in an otherwise diploid cell or organism
• wild type: the typical form of an organism, strain, gene or characteristic as it occurs in nature | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/13%3A_Modern_Understandings_of_Inheritance/13.01%3A_Chromosomal_Theory_and_Genetic_Linkage/13.1A%3A_Chromosomal_Theory_of_Inheritance.txt |
Learning Objectives
• Discuss how linked genes can be inherited separately
Genetic Linkage and Distances
Mendel’s work suggested that traits are inherited independently of each other. Morgan identified a 1:1 ratio between a segregating trait and the X chromosome, suggesting that the random segregation of chromosomes was the physical basis of Mendel’s model. This also demonstrated that linked genes disrupt Mendel’s predicted outcomes. The fact that each chromosome can carry many linked genes explains how individuals can have many more traits than they have chromosomes. However, observations by researchers in Morgan’s laboratory suggested that alleles positioned on the same chromosome were not always inherited together. During meiosis, linked genes somehow became unlinked.
Homologous Recombination
In 1909, Frans Janssen observed chiasmata (the point at which chromatids are in contact with each other and may exchange segments) prior to the first division of meiosis. He suggested that alleles become unlinked when chromosomes physically exchange segments. As chromosomes condensed and paired with their homologs, they appeared to interact at distinct points. Janssen suggested that these points corresponded to regions in which chromosome segments were exchanged. It is now known that the pairing and interaction between homologous chromosomes, known as synapsis, does more than simply organize the homologs for migration to separate daughter cells. When synapsed, homologous chromosomes undergo reciprocal physical exchanges of DNA at their arms in a process called homologous recombination, or more simply, “crossing over.”
Genetic Maps
In 1913, Alfred Sturtevant, a student in Morgan’s laboratory, created the first “chromosome map,” a linear representation of gene order and relative distance on a chromosome.To construct a chromosome map, Sturtevant assumed that genes were ordered serially on threadlike chromosomes. He also assumed that the incidence of recombination between two homologous chromosomes could occur with equal likelihood anywhere along the length of the chromosome. Operating under these assumptions, Sturtevant hypothesized alleles that were far apart on a chromosome were more likely to dissociate during meiosis simply because there was a larger region over which recombination could occur. Conversely, alleles that were close to each other on the chromosome were likely to be inherited together. The average number of crossovers between two alleles, or their recombination frequency, correlated with their genetic distance from each other, relative to the locations of other genes on that chromosome. Sturtevant divided his genetic map into map units, or centimorgans (cM), in which a recombination frequency of 0.01 corresponds to 1 cM.
By representing alleles in a linear map, Sturtevant suggested that genes can range from being perfectly linked (recombination frequency = 0) to being perfectly unlinked (recombination frequency = 0.5) when genes are on different chromosomes or genes are separated very far apart on the same chromosome. Perfectly unlinked genes correspond to the frequencies predicted by Mendel to assort independently in a dihybrid cross. A recombination frequency of 0.5 indicates that 50 percent of offspring are recombinants and the other 50 percent are parental types. That is, every type of allele combination is represented with equal frequency. This allowed Sturtevant to calculate distances between several genes on the same chromosome.
Key Points
• Alleles positioned on the same chromosome are not always inherited together because during meiosis linked genes can became unlinked.
• Frans Janssen suggested chromosomes become unlinked during homologous recombination, a process where homologous chromosomes exchange segments of DNA.
• Alfred Sturtevant hypothesized that alleles that were closer together on a gene were more likely to be inherited together rather than alleles that were farther apart and used measurements of recombination between genes to create the first genetic map.
• When genes are perfectly linked, they have a recombination frequency of 0.
• When genes are unlinked, they have a recombination frequency of 0.5, which means 50 percent of offspring are recombinants and the other 50 percent are parental types.
Key Terms
• homologous recombination: a type of genetic recombination in which nucleotide sequences are exchanged between two similar or identical molecules of DNA
• linkage: the property of genes of being inherited together
• synapsis: the association of homologous maternal and paternal chromosomes during the initial part of meiosis | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/13%3A_Modern_Understandings_of_Inheritance/13.01%3A_Chromosomal_Theory_and_Genetic_Linkage/13.1B%3A_Genetic_Linkage_and_Distances.txt |
Learning Objectives
• Describe a normal human karyotype and discuss the various abnormalities that can be detected using this technique
Identification of Chromosomes
The isolation and microscopic observation of chromosomes forms the basis of cytogenetics and is the primary method by which clinicians detect chromosomal abnormalities in humans. A karyotype is the number and appearance of chromosomes. To obtain a view of an individual’s karyotype, cytologists photograph the chromosomes and then cut and paste each chromosome into a chart, or karyogram, also known as an ideogram.
In a given species, chromosomes can be identified by their number, size, centromere position, and banding pattern. In a human karyotype, autosomes or “body chromosomes” (all of the non–sex chromosomes) are generally organized in approximate order of size from largest (chromosome 1) to smallest (chromosome 22). However, chromosome 21 is actually shorter than chromosome 22. This was discovered after the naming of Down syndrome as trisomy 21, reflecting how this disease results from possessing one extra chromosome 21 (three total). Not wanting to change the name of this important disease, chromosome 21 retained its numbering, despite describing the shortest set of chromosomes. The X and Y chromosomes are not autosomes and are referred to as the sex chromosomes.
The chromosome “arms” projecting from either end of the centromere may be designated as short or long, depending on their relative lengths. The short arm is abbreviated p (for “petite”), whereas the long arm is abbreviated q (because it follows “p” alphabetically). Each arm is further subdivided and denoted by a number. Using this naming system, locations on chromosomes can be described consistently in the scientific literature.
Although Mendel is referred to as the “father of modern genetics,” he performed his experiments with none of the tools that the geneticists of today routinely employ. One such powerful cytological technique is karyotyping, a method in which traits characterized by chromosomal abnormalities can be identified from a single cell. To observe an individual’s karyotype, a person’s cells (like white blood cells) are first collected from a blood sample or other tissue. In the laboratory, the isolated cells are stimulated to begin actively dividing. A chemical called colchicine is then applied to cells to arrest condensed chromosomes in metaphase. Cells are then made to swell using a hypotonic solution so the chromosomes spread apart. Finally, the sample is preserved in a fixative and applied to a slide.
The geneticist then stains chromosomes with one of several dyes to better visualize the distinct and reproducible banding patterns of each chromosome pair. Following staining, the chromosomes are viewed using bright-field microscopy. A common stain choice is the Giemsa stain. Giemsa staining results in approximately 400–800 bands (of tightly coiled DNA and condensed proteins) arranged along all of the 23 chromosome pairs. An experienced geneticist can identify each chromosome based on its characteristic banding pattern. In addition to the banding patterns, chromosomes are further identified on the basis of size and centromere location. To obtain the classic depiction of the karyotype in which homologous pairs of chromosomes are aligned in numerical order from longest to shortest, the geneticist obtains a digital image, identifies each chromosome, and manually arranges the chromosomes into this pattern.
At its most basic, the karyotype may reveal genetic abnormalities in which an individual has too many or too few chromosomes per cell. Examples of this are Down Syndrome, which is identified by a third copy of chromosome 21, and Turner Syndrome, which is characterized by the presence of only one X chromosome in women instead of the normal two. Geneticists can also identify large deletions or insertions of DNA. For instance, Jacobsen Syndrome, which involves distinctive facial features as well as heart and bleeding defects, is identified by a deletion on chromosome 11. Finally, the karyotype can pinpoint translocations, which occur when a segment of genetic material breaks from one chromosome and reattaches to another chromosome or to a different part of the same chromosome. Translocations are implicated in certain cancers, including chronic myelogenous leukemia.
During Mendel’s lifetime, inheritance was an abstract concept that could only be inferred by performing crosses and observing the traits expressed by offspring. By observing a karyotype, today’s geneticists can actually visualize the chromosomal composition of an individual to confirm or predict genetic abnormalities in offspring, even before birth.
Key Points
• A normal human karyotype contains 23 pairs of chromosomes: 22 pairs of autosomes and 1 pair of sex chromosomes, generally arranged in order from largest to smallest.
• The short arm of a chromosome is referred to as the p arm, while the long arm is designated the q arm.
• To observe a karyotype, cells are collected from a blood or tissue sample and stimulated to begin dividing; the chromosomes are arrested in metaphase, preserved in a fixative and applied to a slide where they are stained with a dye to visualize the distinct banding patterns of each chromosome pair.
• A karyotype can be used to visualize abnormalities in the chromosomes, such as an incorrect number of chromosomes, deletions, insertions, or translocations of DNA.
Key Terms
• autosome: any chromosome other than sex chromosomes
• karyotype: the observed characteristics (number, type, shape etc) of the chromosomes of an individual or species
• translocation: a transfer of a chromosomal segment to a new position, especially on a nonhomologous chromosome | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/13%3A_Modern_Understandings_of_Inheritance/13.01%3A_Chromosomal_Theory_and_Genetic_Linkage/13.1C%3A_Identification_of_Chromosomes_and_Karyotypes.txt |
Aneuploidy, an abnormal number of chromosomes in a cell, is caused by nondisjunction, or the failure of chromosomes to separate at meiosis.
Learning Objectives
• Define aneuploidy and explain how this condition results from nondisjunction
Key Points
• Aneuploidy is caused by nondisjunction, which occurs when pairs of homologous chromosomes or sister chromatids fail to separate during meiosis.
• The loss of a single chromosome from a diploid genome is called monosomy (2n-1), while the gain of one chromosome is called trisomy (2n+1).
• If homologous chromosomes fail to separate during meiosis I, the result is no gametes with the normal number (one) of chromosomes.
• If sister chromatids fail to separate during meiosis II, the result is two normal gametes each with one copy of the chromosome, and two abnormal gametes in which one carries two copies and the other carries none.
• Aneuploidy can be lethal or result in serious developmental disorders such as Turner Syndrome (X monosomy) or Downs Syndrome (trisomy 21).
Key Terms
• aneuploidy: the state of possessing a chromosome number that is not an exact multiple of the haploid number
• nondisjunction: the failure of chromosome pairs to separate properly during meiosis
Disorders in Chromosome Number
Of all of the chromosomal disorders, abnormalities in chromosome number are the most obviously identifiable from a karyotype and are referred to as aneuploidy. Aneuploidy is a condition in which one or more chromosomes are present in extra copies or are deficient in number, but not a complete set. To be more specific, the loss of a single chromosome from a diploid genome is called monosomy (2n-1). The gain of one chromosome is called trisomy (2n+1).They are caused by nondisjunction, which occurs when pairs of homologous chromosomes or sister chromatids fail to separate during meiosis. Misaligned or incomplete synapsis, or a dysfunction of the spindle apparatus that facilitates chromosome migration, can cause nondisjunction. The risk of nondisjunction occurring increases with the age of the parents.
Nondisjunction can occur during either meiosis I or II, with differing results. If homologous chromosomes fail to separate during meiosis I, the result is two gametes that lack that particular chromosome and two gametes with two copies of the chromosome. If sister chromatids fail to separate during meiosis II, the result is one gamete that lacks that chromosome, two normal gametes with one copy of the chromosome, and one gamete with two copies of the chromosome. If a gamete with two copies of the chromosome combines with a normal gamete during fertilization, the result is trisomy; if a gamete with no copies of the chromosomes combines with a normal gamete during fertilization, the result is monosomy.
Aneuploidy often results in serious problems such as Turner syndrome, a monosomy in which females may contain all or part of an X chromosome. Monosomy for autosomes is usually lethal in humans and other animals. Klinefelter syndrome is a trisomy genetic disorder in males caused by the presence of one or more X chromosomes. The effects of trisomy are similar to those of monosomy. Down syndrome is the only autosomal trisomy in humans that has a substantial number of survivors one year after birth. Trisomy in chromosome 21 is the cause of Down syndrome; it affects 1 infant in every 800 live births. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/13%3A_Modern_Understandings_of_Inheritance/13.02%3A_Chromosomal_Basis_of_Inherited_Disorders/13.2A%3A_Disorders_in_Chromosome_Number.txt |
Structural rearrangements of chromosomes include both inversions and translocations, which may have detrimental effects on an organism.
Learning Objectives
• Describe the various types of structural rearrangements of chromosomes and how they can impact an organism
Key Points
• A chromosome inversion is the detachment, 180° rotation, and reinsertion of part of a chromosome; this may have no effect on the organism, but if the inversion occurs within a gene or moves a gene away from its regulatory elements it can have an adverse effect.
• Pericentric inversions include the centromere, while paracentric inversions occur outside of the centromere; a pericentric inversion can change the length of the chromosome arms above and below the centromere.
• A pericentric inversion on chromsome 18 appears to have been involved in the evolution of humans.
• A translocation occurs when a segment of a chromosome dissociates and reattaches to a different, nonhomologous chromosome and can be benign or detrimental; in reciprocal translocations, there is no gain or loss of genetic information, so these are usually benign.
Key Terms
• inversion: a segment of DNA in the context of a chromosome that is reversed in orientation relative to a reference karyotype or genome
• translocation: a transfer of a chromosomal segment to a new position, especially on a nonhomologous chromosome
Chromosomal Structural Rearrangements
Cytologists have characterized numerous structural rearrangements in chromosomes, but chromosome inversions and translocations are the most common. Both are identified during meiosis by the adaptive pairing of rearranged chromosomes with their former homologs to maintain appropriate gene alignment. If the genes carried on two homologs are not oriented correctly, a recombination event could result in the loss of genes from one chromosome and the gain of genes on the other. This would produce aneuploid gametes.
Chromosome Inversions
A chromosome inversion is the detachment, 180° rotation, and reinsertion of part of a chromosome. Inversions may occur in nature as a result of mechanical shear, or from the action of transposable elements (special DNA sequences capable of facilitating the rearrangement of chromosome segments with the help of enzymes that cut and paste DNA sequences). Unless they disrupt a gene sequence, inversions only change the orientation of genes and are likely to have milder effects than aneuploid errors. However, altered gene orientation can result in functional changes because regulators of gene expression could be moved out of position with respect to their targets, causing aberrant levels of gene products.
An inversion can be pericentric and include the centromere, or paracentric and occur outside of the centromere. A pericentric inversion that is asymmetric about the centromere can change the relative lengths of the chromosome arms, making these inversions easily identifiable.
When one homologous chromosome undergoes an inversion, but the other does not, the individual is described as an inversion heterozygote. To maintain point-for-point synapsis during meiosis, one homolog must form a loop, and the other homolog must mold around it. Although this topology can ensure that the genes are correctly aligned, it also forces the homologs to stretch and can be associated with regions of imprecise synapsis.
Not all structural rearrangements of chromosomes produce nonviable, impaired, or infertile individuals. In rare instances, such a change can result in the evolution of a new species. In fact, a pericentric inversion in chromosome 18 appears to have contributed to the evolution of humans. This inversion is not present in our closest genetic relatives, the chimpanzees. Humans and chimpanzees differ cytogenetically by pericentric inversions on several chromosomes and by the fusion of two separate chromosomes in chimpanzees that correspond to chromosome two in humans.
The pericentric chromosome 18 inversion is believed to have occurred in early humans following their divergence from a common ancestor with chimpanzees approximately five million years ago. Researchers characterizing this inversion have suggested that approximately 19,000 nucleotide bases were duplicated on 18p, and the duplicated region inverted and reinserted on chromosome 18 of an ancestral human.
A comparison of human and chimpanzee genes in the region of this inversion indicates that two genes—ROCK1 and USP14—that are adjacent on chimpanzee chromosome 17 (which corresponds to human chromosome 18) are more distantly positioned on human chromosome 18. This suggests that one of the inversion breakpoints occurred between these two genes. Interestingly, humans and chimpanzees express USP14 at distinct levels in specific cell types, including cortical cells and fibroblasts. Perhaps the chromosome 18 inversion in an ancestral human repositioned specific genes and reset their expression levels in a useful way. Because both ROCK1 and USP14 encode cellular enzymes, a change in their expression could alter cellular function. It is not known how this inversion contributed to hominid evolution, but it appears to be a significant factor in the divergence of humans from other primates.
Translocations
A translocation occurs when a segment of a chromosome dissociates and reattaches to a different, nonhomologous chromosome. Translocations can be benign or have devastating effects depending on how the positions of genes are altered with respect to regulatory sequences. Notably, specific translocations have been associated with several cancers and with schizophrenia. Reciprocal translocations result from the exchange of chromosome segments between two nonhomologous chromosomes such that there is no gain or loss of genetic information. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/13%3A_Modern_Understandings_of_Inheritance/13.02%3A_Chromosomal_Basis_of_Inherited_Disorders/13.2B%3A_Chromosomal_Structural_Rearrangements.txt |
The presence of extra X chromosomes in a cell is compensated for by X-inactivation in which all but one X chromosome are silenced.
Learning Objectives
• Explain how and why X inactivation occurs in humans
Key Points
• Extra copies of the X chromosome are silenced by becoming Barr bodies.
• X chromosomal abnormalities are typically associated with mild mental and physical defects, as well as sterility.
• Conditions associated with aneuploidy of the sex chromosomes include individuals with three X chromosomes, called triplo-X; the XXY genotype, known as Klinefelter syndrome; and Turner syndrome, characterized as X monosomy.
• X-inactivation is a form of dosage compensation, in which an organism attempts to equalize the amount of X chromosome gene products in males and females.
• Since males only have one X chromosome, females inactivate one of theirs so that only one X chromosome is active in each gender.
Key Terms
• dosage compensation: a genetic regulatory mechanism that equalizes the phenotypic expression of characteristics determined by genes on the X chromosome so that they are equally expressed in males and females.
• Barr body: a sex chromosome inactivated by packing in heterochromatin
• X inactivation: a process by which one of the two copies of the X chromosome present in female mammals is inactivated
Sex Chromosome Nondisjunction in Humans
Humans display dramatic deleterious effects with autosomal trisomies and monosomies. Therefore, it may seem counterintuitive that human females and males can function normally, despite carrying different numbers of the X chromosome. Rather than a gain or loss of autosomes, variations in the number of X chromosomes are associated with relatively mild effects. In part, this occurs because of a molecular process called X inactivation. Early in development, when female mammalian embryos consist of just a few thousand cells (relative to trillions in the newborn), one X chromosome in each cell inactivates by tightly condensing into a quiescent (dormant) structure called a Barr body. The chance that an X chromosome (maternally or paternally derived ) is inactivated in each cell is random, but once the inactivation occurs, all cells derived from that single cell will have the same inactive X chromosome or Barr body.
By this process, a phenomenon called dosage compensation is achieved. Females possess two X chromosomes, while males have only one; therefore, if both X chromosomes remained active in the female, they would produce twice as much product from the genes on the X chromosomes as males.
So how does X-inactivation help alleviate the effects of extra X chromosomes? An individual carrying an abnormal number of X chromosomes will inactivate all but one X chromosome in each of her cells. If three X chromosomes are present, the cell will inactivate two of them. If four X chromosomes are present, three will be inactivated, and so on. This results in an individual that is relatively phenotypically normal. However, even inactivated X chromosomes continue to express a few genes, and X chromosomes must reactivate for the proper maturation of female ovaries. As a result, X-chromosomal abnormalities are typically associated with mild mental and physical defects, as well as sterility. If the X chromosome is absent altogether, the individual will not develop in utero.
Several errors in sex chromosome number have been characterized. Individuals with three X chromosomes, called triplo-X, are phenotypically female, but express developmental delays and reduced fertility. The XXY genotype, corresponding to one type of Klinefelter syndrome, corresponds to phenotypically male individuals with small testes, enlarged breasts, and reduced body hair. More complex types of Klinefelter syndrome exist in which the individual has as many as five X chromosomes. In all types, every X chromosome except one undergoes inactivation to compensate for the excess genetic dosage. This can be seen as several Barr bodies in each cell nucleus. Turner syndrome, characterized as an X0 genotype (i.e., only a single sex chromosome), corresponds to a phenotypically female individual with short stature, webbed skin in the neck region, hearing and cardiac impairments, and sterility.
Duplications and Deletions
In addition to the loss or gain of an entire chromosome, a chromosomal segment may be duplicated or lost. Duplications and deletions often produce offspring that survive but exhibit physical and mental abnormalities. Duplicated chromosomal segments may fuse to existing chromosomes or may be free in the nucleus. Cri-du-chat (from the French for “cry of the cat”) is a syndrome associated with nervous system abnormalities and identifiable physical features that result from a deletion of most of 5p (the small arm of chromosome 5). Infants with this genotype emit a characteristic high-pitched cry on which the disorder’s name is based. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/13%3A_Modern_Understandings_of_Inheritance/13.02%3A_Chromosomal_Basis_of_Inherited_Disorders/13.2C%3A_X-Inactivation.txt |
The discovery of DNA is generally credited to Watson and Crick, but many other scientists contributed to the discovery.
Learning Objectives
• Explain the sequence of events leading up to the discovery of the structure of DNA
Key Points
• DNA is one of the most basic molecules of life; it carries genetic instructions for the development, functioning and reproduction of all known living organisms.
• The discovery of DNA’s double-helix structure is largely credited to the scientists Watson and Crick, for which they won a Nobel Prize.
• However, the X-ray crystallography work of Rosalind Franklin and Erwin Chargaff’s work in discovering the composition of DNA were instrumental to the discovery of DNA’s structure.
Key Terms
• double helix: The structure formed by double-stranded molecules of nucleic acids such as DNA.
What is DNA?
Deoxyribonucleic acid (DNA) is a molecule that carries most of the genetic instructions used in the development, functioning and reproduction of all known living organisms and many viruses.
DNA is a nucleic acid; alongside proteins and carbohydrates, nucleic acids are one of the three major macromolecules essential for all known forms of life. DNA stores biological information and is involved in the expression of traits in all living organisms.
The Path to Discovery
In the 1950s, Francis Crick and James Watson worked together to determine the structure of DNA at the University of Cambridge, England. At the time, other scientists like Linus Pauling and Maurice Wilkins were also actively exploring this field. Pauling had discovered the secondary structure of proteins using X-ray crystallography.
Chargaff’s Rule
Erwin Chargaff met Francis Crick and James D. Watson at Cambridge in 1952, and, despite not getting along with them personally, he explained his findings to them. Chargaff’s Rule showed that in natural DNA, the number of guanine units equals the number of cytosine units and the number of adenine units equals the number of thymine units. This strongly hinted towards the base pair makeup of the DNA. Chargaff’s research would help the Watson and Crick laboratory team to deduce the double helical structure of DNA.
Franklin and X-Ray Diffraction
In Wilkins’ lab, researcher Rosalind Franklin used X-ray diffraction methods to understand the structure of DNA. Watson and Crick were able to piece together the puzzle of the DNA molecule on the basis of Franklin’s data, because Crick had also studied X-ray diffraction. In 1962, James Watson, Francis Crick, and Maurice Wilkins were awarded the Nobel Prize in Medicine.
Unfortunately by then, Franklin had died. Nobel prizes are not awarded posthumously, and though her work was crucial to the discovery of DNA, Franklin was never nominated for a Nobel Prize. Francis Crick, James Watson, and Maurice Wilkins were awarded a Nobel Prize for the discovery of the structure of DNA in 1962. There is still much controversy on how her image was given to Watson and Crick and why she was not given due credit.
14.1B: Modern Applications of DNA
DNA has many applications in a variety of fields including forensics and medicine.
Learning Objectives
• Explain why DNA is a practical tool in various fields, such as forensics and medicine
Key Points
• DNA is unique to each individual, and therefore can be used for identification purposes.
• The human genome consists of about 3 billion base pairs, corresponding to about 20,000 to 25,000 functional genes.
• Each person’s DNA is inherited from their parents: 23 chromosomes from the mother, and 23 chromosomes from the father.
Key Terms
• genotype: The combination of alleles, situated on corresponding chromosomes, that determines a specific trait of an individual.
• zygote: The single cell that arises from the union of two gametes; in animals, the cell that arises from the union of sperm and ovum.
• gene: A unit of heredity; the functional units of chromosomes that determine specific characteristics by coding for specific RNAs or proteins.
• phenotype: The appearance of an organism based on a multifactorial combination of genetic traits and environmental factors.
The acronym “DNA” has become synonymous with solving crimes, testing for paternity, identifying human remains, and genetic testing. DNA can be retrieved from hair, blood, or saliva. Each person’s DNA sequences are unique, and it is possible to detect differences between individuals within a species on the basis of these unique features. DNA testing can also be used to identify pathogens, identify biological remains in archaeological digs, trace disease outbreaks, and study human migration patterns. In the medical field, DNA is used in diagnostics, new vaccine development, and cancer therapy. It is now also possible to determine predispositions to some diseases by looking at genes.
Cloning
Reproductive cloning is a method used to make a clone or an identical copy of an entire multicellular organism.
In cloning both the original organism and the clone have identical DNA. Identical twins are, in one sense, clones of each other; they have identical DNA, having developed from the same fertilized egg.
Cloning became an issue in scientific ethics when a sheep became the first mammal cloned from an adult cell in 1996.
Since then several animals such as horses, bulls, and goats have been successfully cloned, although these individuals often exhibit facial, limb, and cardiac abnormalities.
There have been attempts at producing cloned human embryos as sources of embryonic stem cells, sometimes referred to as ‘cloning for therapeutic purposes’. Therapeutic cloning produces stem cells to attempt to remedy detrimental diseases or defects (unlike reproductive cloning, which aims to reproduce an organism). Still, therapeutic cloning efforts have met with resistance because of bioethical considerations.
CRISPR
CRISPR (Clustered, Regularly-Interspaced Short Palindromic Repeats) allows scientists to edit genomes, far better than older techniques for gene splicing and editing. The CRISPR technique has enormous potential application, including altering the germline of humans, animals and other organisms, and modifying the genes of food crops.
Ethical concerns have surfaced about this biotechnology and the prospect of editing the human germline and making so-called ‘designer babies’.
CRISPR Technique: This movie goes through the process of CRISPR.
Genetically Modified Organisms
A genetically modified organism (GMO) is any organism whose genetic material has been altered using genetic engineering techniques. GMOs are a source of medicines and genetically modified foods and are also widely used in scientific research, along with the production of other goods.
Genetic modification involves the mutation, insertion, or deletion of genes. Inserted genes usually come from a different species in a form of horizontal gene-transfer.
Bacteria, plants, and animals have been genetically modified since the early 1970s for academic, medical, agricultural, and industrial purposes. In the US, GMOs such as Roundup-Ready soybeans and borer-resistant corn are part of many common processed foods. As in many of these biotechnology areas there is considerable controversy in the use of GMOs. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/14%3A_DNA_Structure_and_Function/14.01%3A_Historical_Basis_of_Modern_Understanding/14.1A%3A__Discovery_of_DNA.txt |
DNA is a double helix of two anti-parallel, complementary strands having a phosphate-sugar backbone with nitrogenous bases stacked inside.
Learning Objectives
• Describe the structure of DNA and summarize the importance of DNA sequencing
Key Points
• The two DNA strands are anti-parallel in nature; that is, the 3′ end of one strand faces the 5′ end of the other strand.
• The nucleotides that comprise DNA contain a nitrogenous base, a deoxyribose sugar, and a phosphate group which covalently link with other nucleotides to form phosphodiester bonds.
• Nucleotide bases can be classified as purines (containing a double-ring structure) or pyrimidines (containing a single-ring structure).
• Adenine (purine) and thymine (pyrimidine) are complementary base pairs as are guanine (purine) and cytosine (pyrimidine).
• DNA sequencing is the process of determining the precise order of nucleotides within a DNA molecule.
Key Terms
• deoxyribose: a derivative of the pentose sugar ribose in which the 2′ hydroxyl (-OH) is reduced to a hydrogen (H); a constituent of the nucleotides that comprise deoxyribonucleic acid, or DNA
• hydrogen bond: A weak bond in which a hydrogen atom already covalently bonded to a oxygen or nitrogen atom in one molecule is attracted to an electronegative atom (usually nitrogen or oxygen) in the same or different molecule.
• nucleotide: the monomer comprising DNA or RNA molecules; consists of a nitrogenous heterocyclic base that can be a purine or pyrimidine, a five-carbon pentose sugar, and a phosphate group
The monomeric building blocks of DNA are deoxyribomononucleotides (usually referred to as just nucleotides), and DNA is formed from linear chains, or polymers, of these nucleotides. The components of the nucleotide used in DNA synthesis are a nitrogenous base, a deoxyribose, and a phosphate group. The nucleotide is named depending on which nitrogenous base is present. The nitrogenous base can be a purine such as adenine (A) and guanine (G), characterized by double-ring structures, or a pyrimidine such as cytosine (C) and thymine (T), characterized by single-ring structures. In polynucleotides (the linear polymers of nucleotides) the nucleotides are connected to each other by covalent bonds known as phosphodiester bonds or phosphodiester linkages.
James Watson and Francis Crick, with some help from Rosalind Franklin and Maurice Wilkins, are credited with figuring out the structure of DNA. Watson and Crick proposed that DNA is made up of two polynucleotide strands that are twisted around each other to form a right-handed helix.
The two polynucleotide strands are anti-parallel in nature. That is, they run in opposite directions.
The sugars and phosphates of the nucleotides form the backbone of the structure, whereas the pairs of nitrogenous bases are pointed towards the interior of the molecule.
The twisting of the two strands around each other results in the formation of uniformly-spaced major and minor grooves bordered by the sugar-phosphate backbones of the two strands.
The diameter of the DNA double helix is 2 nm and is uniform throughout. Only the pairing between a purine and pyrimidine can explain the uniform diameter. That is to say, at each point along the DNA molecule, the two sugar phosphate backbones are always separated by three rings, two from a purine and one from a pyrimidine.
The two strands are held together by base pairing between nitrogenous bases of one strand and nitrogenous bases from the other strand. Base pairing takes place between a purine and pyrimidine stabilized by hydrogen bonds: A pairs with T via two hydrogen bonds and G pairs with C via three hydrogen bonds.
The interior basepairs rotate with respect to one another, but are also stacked on top of each other when the molecule is viewed looking up or down its long axis.
Each base pair is separated from the previous base pair by a height of 0.34 nm and each 360o turn of the helix travels 3.4 nm along the long axis of the molecule. Therefore, ten base pairs are present per turn of the helix.
DNA sequencing is the process of determining the precise order of nucleotides within a DNA molecule. Rapid DNA sequencing methods has greatly accelerated biological and medical research and discovery. Knowledge of DNA sequences has become indispensable for basic biological research, and in numerous applied fields such as diagnostics, biotechnology, forensic biology, and biological systematics. The rapid speed of sequencing attained with modern technology has been instrumental in obtaining complete DNA sequences, or genomes, of numerous types and species of life, including the human genome and those of other animal, plant, and microbial species. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/14%3A_DNA_Structure_and_Function/14.02%3A_DNA_Structure_and_Sequencing/14.2A%3A_The_Structure_and_Sequence_of_DNA.txt |
DNA sequencing techniques are used to determine the order of nucleotides (A,T,C,G) in a DNA molecule.
Learning Objectives
• Differentiate among the techniques used to sequence DNA
Key Points
• Genome sequencing will greatly advance our understanding of genetic biology and has vast potential for medical diagnosis and treatment.
• DNA sequencing technologies have gone through at least three “generations”: Sanger sequencing and Gilbert sequencing were first-generation, pyrosequencing was second-generation, and Illumina sequencing is next-generation.
• Sanger sequencing is based on the use of chain terminators, ddNTPs, that are added to growing DNA strands and terminate synthesis at different points.
• Illumina sequencing involves running up to 500,000,000 different sequencing reactions simultaneously on a single small slide. It makes use of a modified replication reaction and uses fluorescently-tagged nucleotides.
• Shotgun sequencing is a technique for determining the sequence of entire chromosomes and entire genomes based on producing random fragments of DNA that are then assembled by computers which order fragments by finding overlapping ends.
Key Terms
• DNA sequencing: a technique used in molecular biology that determines the sequence of nucleotides (A, C, G, and T) in a particular region of DNA
• dideoxynucleotide: any nucleotide formed from a deoxynucleotide by loss of an a second hydroxyl group from the deoxyribose group
• in vitro: any biochemical process done outside of its natural biological environment, such as in a test tube, petri dish, etc. (from the Latin for “in glass”)
DNA Sequencing Techniques
While techniques to sequence proteins have been around since the 1950s, techniques to sequence DNA were not developed until the mid-1970s, when two distinct sequencing methods were developed almost simultaneously, one by Walter Gilbert’s group at Harvard University, the other by Frederick Sanger’s group at Cambridge University. However, until the 1990s, the sequencing of DNA was a relatively expensive and long process. Using radiolabeled nucleotides also compounded the problem through safety concerns. With currently-available technology and automated machines, the process is cheaper, safer, and can be completed in a matter of hours. The Sanger sequencing method was used for the human genome sequencing project, which was finished its sequencing phase in 2003, but today both it and the Gilbert method have been largely replaced by better methods.
Sanger Sequencing
The Sanger method is also known as the dideoxy chain termination method. This sequencing method is based on the use of chain terminators, the dideoxynucleotides (ddNTPs). The dideoxynucleotides, or ddNTPSs, differ from deoxynucleotides by the lack of a free 3′ OH group on the five-carbon sugar. If a ddNTP is added to a growing DNA strand, the chain is not extended any further because the free 3′ OH group needed to add another nucleotide is not available. By using a predetermined ratio of deoxyribonucleotides to dideoxynucleotides, it is possible to generate DNA fragments of different sizes when replicating DNA in vitro.
A Sanger sequencing reaction is just a modified in vitro DNA replication reaction. As such the following components are needed: template DNA (which will the be DNA whose sequence will be determined), DNA Polymerase to catalyze the replication reactions, a primer that basepairs prior to the portion of the DNA you want to sequence, dNTPs, and ddNTPs. The ddNTPs are what distinguish a Sanger sequencing reaction from just a replication reaction. Most of the time in a Sanger sequencing reaction, DNA Polymerase will add a proper dNTP to the growing strand it is synthesizing in vitro. But at random locations, it will instead add a ddNTP. When it does, that strand will be terminated at the ddNTP just added. If enough template DNAs are included in the reaction mix, each one will have the ddNTP inserted at a different random location, and there will be at least one DNA terminated at each different nucleotide along its length for as long as the in vitro reaction can take place (about 900 nucleotides under optimal conditions.)
The ddNTPs which terminate the strands have fluorescent labels covalently attached to them. Each of the four ddNTPs carries a different label, so each different ddNTP will fluoresce a different color.
After the reaction is over, the reaction is subject to capillary electrophoresis. All the newly synthesized fragments, each terminated at a different nucleotide and so each a different length, are separated by size. As each differently-sized fragment exits the capillary column, a laser excites the flourescent tag on its terminal nucleotide. From the color of the resulting flouresence, a computer can keep track of which nucleotide was present as the terminating nucleotide. The computer also keeps track of the order in which the terminating nucleotides appeared, which is the sequence of the DNA used in the original reaction.
Second Generation and Next-generation Sequencing
The Sanger and Gilbert methods of sequencing DNA are often called “first-generation” sequencing because they were the first to be developed. In the late 1990s, new methods, called second-generation sequencing methods, that were faster and cheaper, began to be developed. The most popular, widely-used second-generation sequencing method was one called Pyrosequencing.
Today a number of newer sequencing methods are available and others are in the process of being developed. These are often called next-generation sequencing methods. The most widely-used sequencing method currently is one called Illumina sequencing (after the name of the company which commercialized the technique), but numerous competing methods are in the developmental pipeline and may supplant Illumina sequencing.
In Illumina sequencing, up to 500,000,000 separate sequencing reactions are run simultaneously on a single slide (the size of a microscope slide) put into a single machine. Each reaction is analyzed separately and the sequences generated from all 500 million DNAs are stored in an attached computer. Each sequencing reaction is a modified replication reaction involving flourescently-tagged nucleotides, but no chain-terminating dideoxy nucleotides are needed.
When the human genome was first sequenced using Sanger sequencing, it took several years, hundreds of labs working together, and a cost of around \$100 million to sequence it to almost completion. Next generation sequencing can sequence a comparably-sized genome in a matter of days, using a single machine, at a cost of under \$10,000. Many researchers have set a goal of improving sequencing methods even more until a single human genome can be sequenced for under \$1000.
Shotgun Sequencing
Sanger sequence can only produce several hundred nucleotides of sequence per reaction. Most next-generation sequencing techniques generate even smaller blocks of sequence. Genomes are made up of chromosomes which are tens to hundreds of millions of basepairs long. They can only be sequenced in tiny fragments and the tiny fragments have to put in the correct order to generate the uninterrupted genome sequence. Most genomic sequencing projects today make use of an approach called whole genome shotgun sequencing.
Whole genome shotgun sequencing involves isolating many copies of the chromosomal DNA of interest. The chromosomes are all fragmented into sizes small enough to be sequenced (a few hundred basepairs) at random locations. As a result, each copy of the same chromosome is fragmented at different locations and the fragments from the same part of the chromosome will overlap each other. Each fragment is sequenced and sophisticated computer algorithms compare all the different fragments to find which overlaps with which. By lining up the overlapped regions, a process called tiling, the computer can find the largest possible continuous sequences that can be generated from the fragments. Ultimately, the sequence of entire chromosomes are assembled.
Genome sequencing will greatly advance our understanding of genetic biology. It has vast potential for medical diagnosis and treatment.
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• OpenStax College, DNA Structure and Sequencing. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44486/latest...14_02_04ab.jpg. License: CC BY: Attribution | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/14%3A_DNA_Structure_and_Function/14.02%3A_DNA_Structure_and_Sequencing/14.2B%3A_DNA_Sequencing_Techniques.txt |
DNA replication uses a semi-conservative method that results in a double-stranded DNA with one parental strand and a new daughter strand.
Learning Objectives
• Explain how the Meselson and Stahl experiment conclusively established that DNA replication is semi-conservative.
Key Points
• There were three models suggested for DNA replication: conservative, semi-conservative, and dispersive.
• The conservative method of replication suggests that parental DNA remains together and newly-formed daughter strands are also together.
• The semi-conservative method of replication suggests that the two parental DNA strands serve as a template for new DNA and after replication, each double-stranded DNA contains one strand from the parental DNA and one new (daughter) strand.
• The dispersive method of replication suggests that, after replication, the two daughter DNAs have alternating segments of both parental and newly-synthesized DNA interspersed on both strands.
• Meselson and Stahl, using E. coli DNA made with two nitrogen istopes (14N and 15N) and density gradient centrifugation, determined that DNA replicated via the semi-conservative method of replication.
Key Terms
• DNA replication: a biological process occuring in all living organisms that is the basis for biological inheritance
• isotope: any of two or more forms of an element where the atoms have the same number of protons, but a different number of neutrons within their nuclei
Basics of DNA Replication
Watson and Crick’s discovery that DNA was a two-stranded double helix provided a hint as to how DNA is replicated. During cell division, each DNA molecule has to be perfectly copied to ensure identical DNA molecules to move to each of the two daughter cells. The double-stranded structure of DNA suggested that the two strands might separate during replication with each strand serving as a template from which the new complementary strand for each is copied, generating two double-stranded molecules from one.
Models of Replication
There were three models of replication possible from such a scheme: conservative, semi-conservative, and dispersive. In conservative replication, the two original DNA strands, known as the parental strands, would re-basepair with each other after being used as templates to synthesize new strands; and the two newly-synthesized strands, known as the daughter strands, would also basepair with each other; one of the two DNA molecules after replication would be “all-old” and the other would be “all-new”. In semi-conservative replication, each of the two parental DNA strands would act as a template for new DNA strands to be synthesized, but after replication, each parental DNA strand would basepair with the complementary newly-synthesized strand just synthesized, and both double-stranded DNAs would include one parental or “old” strand and one daughter or “new” strand. In dispersive replication, after replication both copies of the new DNAs would somehow have alternating segments of parental DNA and newly-synthesized DNA on each of their two strands.
To determine which model of replication was accurate, a seminal experiment was performed in 1958 by two researchers: Matthew Meselson and Franklin Stahl.
Meselson and Stahl
Meselson and Stahl were interested in understanding how DNA replicates. They grew E. coli for several generations in a medium containing a “heavy” isotope of nitrogen (15N) that is incorporated into nitrogenous bases and, eventually, into the DNA. The E. coli culture was then shifted into medium containing the common “light” isotope of nitrogen (14N) and allowed to grow for one generation. The cells were harvested and the DNA was isolated. The DNA was centrifuged at high speeds in an ultracentrifuge in a tube in which a cesium chloride density gradient had been established. Some cells were allowed to grow for one more life cycle in 14N and spun again.
During the density gradient ultracentrifugation, the DNA was loaded into a gradient (Meselson and Stahl used a gradient of cesium chloride salt, although other materials such as sucrose can also be used to create a gradient) and spun at high speeds of 50,000 to 60,000 rpm. In the ultracentrifuge tube, the cesium chloride salt created a density gradient, with the cesium chloride solution being more dense the farther down the tube you went. Under these circumstances, during the spin the DNA was pulled down the ultracentrifuge tube by centrifugal force until it arrived at the spot in the salt gradient where the DNA molecules’ density matched that of the surrounding salt solution. At the point, the molecules stopped sedimenting and formed a stable band. By looking at the relative positions of bands of molecules run in the same gradients, you can determine the relative densities of different molecules. The molecules that form the lowest bands have the highest densities.
DNA from cells grown exclusively in 15N produced a lower band than DNA from cells grown exclusively in 14N. So DNA grown in 15N had a higher density, as would be expected of a molecule with a heavier isotope of nitrogen incorporated into its nitrogenous bases. Meselson and Stahl noted that after one generation of growth in 14N (after cells had been shifted from 15N), the DNA molecules produced only single band intermediate in position in between DNA of cells grown exclusively in 15N and DNA of cells grown exclusively in 14N. This suggested either a semi-conservative or dispersive mode of replication. Conservative replication would have resulted in two bands; one representing the parental DNA still with exclusively 15N in its nitrogenous bases and the other representing the daughter DNA with exclusively 14N in its nitrogenous bases. The single band actually seen indicated that all the DNA molecules contained equal amounts of both 15N and 14N.
The DNA harvested from cells grown for two generations in 14N formed two bands: one DNA band was at the intermediate position between 15N and 14N and the other corresponded to the band of exclusively 14N DNA. These results could only be explained if DNA replicates in a semi-conservative manner. Dispersive replication would have resulted in exclusively a single band in each new generation, with the band slowly moving up closer to the height of the 14N DNA band. Therefore, dispersive replication could also be ruled out.
Meselson and Stahl’s results established that during DNA replication, each of the two strands that make up the double helix serves as a template from which new strands are synthesized. The new strand will be complementary to the parental or “old” strand and the new strand will remain basepaired to the old strand. So each “daughter” DNA actually consists of one “old” DNA strand and one newly-synthesized strand. When two daughter DNA copies are formed, they have the identical sequences to one another and identical sequences to the original parental DNA, and the two daughter DNAs are divided equally into the two daughter cells, producing daughter cells that are genetically identical to one another and genetically identical to the parent cell. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/14%3A_DNA_Structure_and_Function/14.03%3A_DNA_Replication/14.3A%3A_Basics_of_DNA_Replication.txt |
Prokaryotic DNA is replicated by DNA polymerase III in the 5′ to 3′ direction at a rate of 1000 nucleotides per second.
Learning Objectives
• Explain the functions of the enzymes involved in prokaryotic DNA replication
Key Points
• Helicase separates the DNA to form a replication fork at the origin of replication where DNA replication begins.
• Replication forks extend bi-directionally as replication continues.
• Okazaki fragments are formed on the lagging strand, while the leading strand is replicated continuously.
• DNA ligase seals the gaps between the Okazaki fragments.
• Primase synthesizes an RNA primer with a free 3′-OH, which DNA polymerase III uses to synthesize the daughter strands.
Key Terms
• DNA replication: a biological process occuring in all living organisms that is the basis for biological inheritance
• helicase: an enzyme that unwinds the DNA helix ahead of the replication machinery
• origin of replication: a particular sequence in a genome at which replication is initiated
DNA Replication in Prokaryotes
DNA replication employs a large number of proteins and enzymes, each of which plays a critical role during the process. One of the key players is the enzyme DNA polymerase, which adds nucleotides one by one to the growing DNA chain that are complementary to the template strand. The addition of nucleotides requires energy; this energy is obtained from the nucleotides that have three phosphates attached to them, similar to ATP which has three phosphate groups attached. When the bond between the phosphates is broken, the energy released is used to form the phosphodiester bond between the incoming nucleotide and the growing chain. In prokaryotes, three main types of polymerases are known: DNA pol I, DNA pol II, and DNA pol III. DNA pol III is the enzyme required for DNA synthesis; DNA pol I and DNA pol II are primarily required for repair.
There are specific nucleotide sequences called origins of replication where replication begins. In E. coli, which has a single origin of replication on its one chromosome (as do most prokaryotes), it is approximately 245 base pairs long and is rich in AT sequences. The origin of replication is recognized by certain proteins that bind to this site. An enzyme called helicase unwinds the DNA by breaking the hydrogen bonds between the nitrogenous base pairs. ATP hydrolysis is required for this process. As the DNA opens up, Y-shaped structures called replication forks are formed. Two replication forks at the origin of replication are extended bi-directionally as replication proceeds. Single-strand binding proteins coat the strands of DNA near the replication fork to prevent the single-stranded DNA from winding back into a double helix. DNA polymerase is able to add nucleotides only in the 5′ to 3′ direction (a new DNA strand can be extended only in this direction). It also requires a free 3′-OH group to which it can add nucleotides by forming a phosphodiester bond between the 3′-OH end and the 5′ phosphate of the next nucleotide. This means that it cannot add nucleotides if a free 3′-OH group is not available. Another enzyme, RNA primase, synthesizes an RNA primer that is about five to ten nucleotides long and complementary to the DNA, priming DNA synthesis. A primer provides the free 3′-OH end to start replication. DNA polymerase then extends this RNA primer, adding nucleotides one by one that are complementary to the template strand.
The replication fork moves at the rate of 1000 nucleotides per second. DNA polymerase can only extend in the 5′ to 3′ direction, which poses a slight problem at the replication fork. As we know, the DNA double helix is anti-parallel; that is, one strand is in the 5′ to 3′ direction and the other is oriented in the 3′ to 5′ direction. One strand (the leading strand), complementary to the 3′ to 5′ parental DNA strand, is synthesized continuously towards the replication fork because the polymerase can add nucleotides in this direction. The other strand (the lagging strand), complementary to the 5′ to 3′ parental DNA, is extended away from the replication fork in small fragments known as Okazaki fragments, each requiring a primer to start the synthesis. Okazaki fragments are named after the Japanese scientist who first discovered them.
The leading strand can be extended by one primer alone, whereas the lagging strand needs a new primer for each of the short Okazaki fragments. The overall direction of the lagging strand will be 3′ to 5′, while that of the leading strand will be 5′ to 3′. The sliding clamp (a ring-shaped protein that binds to the DNA) holds the DNA polymerase in place as it continues to add nucleotides. Topoisomerase prevents the over-winding of the DNA double helix ahead of the replication fork as the DNA is opening up; it does so by causing temporary nicks in the DNA helix and then resealing it. As synthesis proceeds, the RNA primers are replaced by DNA. The primers are removed by the exonuclease activity of DNA pol I, while the gaps are filled in by deoxyribonucleotides. The nicks that remain between the newly-synthesized DNA (that replaced the RNA primer) and the previously-synthesized DNA are sealed by the enzyme DNA ligase that catalyzes the formation of phosphodiester linkage between the 3′-OH end of one nucleotide and the 5′ phosphate end of the other fragment.
The table summarizes the enzymes involved in prokaryotic DNA replication and the functions of each. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/14%3A_DNA_Structure_and_Function/14.03%3A_DNA_Replication/14.3B%3A_DNA_Replication_in_Prokaryotes.txt |
DNA replication in eukaryotes occurs in three stages: initiation, elongation, and termination, which are aided by several enzymes.
Learning Objectives
• Describe how DNA is replicated in eukaryotes
Key Points
• During initiation, proteins bind to the origin of replication while helicase unwinds the DNA helix and two replication forks are formed at the origin of replication.
• During elongation, a primer sequence is added with complementary RNA nucleotides, which are then replaced by DNA nucleotides.
• During elongation the leading strand is made continuously, while the lagging strand is made in pieces called Okazaki fragments.
• During termination, primers are removed and replaced with new DNA nucleotides and the backbone is sealed by DNA ligase.
Key Terms
• origin of replication: a particular sequence in a genome at which replication is initiated
• leading strand: the template strand of the DNA double helix that is oriented so that the replication fork moves along it in the 3′ to 5′ direction
• lagging strand: the strand of the template DNA double helix that is oriented so that the replication fork moves along it in a 5′ to 3′ manner
Because eukaryotic genomes are quite complex, DNA replication is a very complicated process that involves several enzymes and other proteins. It occurs in three main stages: initiation, elongation, and termination.
Initiation
Eukaryotic DNA is bound to proteins known as histones to form structures called nucleosomes. During initiation, the DNA is made accessible to the proteins and enzymes involved in the replication process. There are specific chromosomal locations called origins of replication where replication begins. In some eukaryotes, like yeast, these locations are defined by having a specific sequence of basepairs to which the replication initiation proteins bind. In other eukaryotes, like humans, there does not appear to be a consensus sequence for their origins of replication. Instead, the replication initiation proteins might identify and bind to specific modifications to the nucleosomes in the origin region.
Certain proteins recognize and bind to the origin of replication and then allow the other proteins necessary for DNA replication to bind the same region. The first proteins to bind the DNA are said to “recruit” the other proteins. Two copies of an enzyme called helicase are among the proteins recruited to the origin. Each helicase unwinds and separates the DNA helix into single-stranded DNA. As the DNA opens up, Y-shaped structures called replication forks are formed. Because two helicases bind, two replication forks are formed at the origin of replication; these are extended in both directions as replication proceeds creating a replication bubble. There are multiple origins of replication on the eukaryotic chromosome which allow replication to occur simultaneously in hundreds to thousands of locations along each chromosome.
Elongation
During elongation, an enzyme called DNA polymerase adds DNA nucleotides to the 3′ end of the newly synthesized polynucleotide strand. The template strand specifies which of the four DNA nucleotides (A, T, C, or G) is added at each position along the new chain. Only the nucleotide complementary to the template nucleotide at that position is added to the new strand.
DNA polymerase contains a groove that allows it to bind to a single-stranded template DNA and travel one nucleotide at at time. For example, when DNA polymerase meets an adenosine nucleotide on the template strand, it adds a thymidine to the 3′ end of the newly synthesized strand, and then moves to the next nucleotide on the template strand. This process will continue until the DNA polymerase reaches the end of the template strand.
DNA polymerase cannot initiate new strand synthesis; it only adds new nucleotides at the 3′ end of an existing strand. All newly synthesized polynucleotide strands must be initiated by a specialized RNA polymerase called primase. Primase initiates polynucleotide synthesis and by creating a short RNA polynucleotide strand complementary to template DNA strand. This short stretch of RNA nucleotides is called the primer. Once RNA primer has been synthesized at the template DNA, primase exits, and DNA polymerase extends the new strand with nucleotides complementary to the template DNA.
Eventually, the RNA nucleotides in the primer are removed and replaced with DNA nucleotides. Once DNA replication is finished, the daughter molecules are made entirely of continuous DNA nucleotides, with no RNA portions.
The Leading and Lagging Strands
DNA polymerase can only synthesize new strands in the 5′ to 3′ direction. Therefore, the two newly-synthesized strands grow in opposite directions because the template strands at each replication fork are antiparallel. The “leading strand” is synthesized continuously toward the replication fork as helicase unwinds the template double-stranded DNA.
The “lagging strand” is synthesized in the direction away from the replication fork and away from the DNA helicase unwinds. This lagging strand is synthesized in pieces because the DNA polymerase can only synthesize in the 5′ to 3′ direction, and so it constantly encounters the previously-synthesized new strand. The pieces are called Okazaki fragments, and each fragment begins with its own RNA primer.
Termination
Eukaryotic chromosomes have multiple origins of replication, which initiate replication almost simultaneously. Each origin of replication forms a bubble of duplicated DNA on either side of the origin of replication. Eventually, the leading strand of one replication bubble reaches the lagging strand of another bubble, and the lagging strand will reach the 5′ end of the previous Okazaki fragment in the same bubble.
DNA polymerase halts when it reaches a section of DNA template that has already been replicated. However, DNA polymerase cannot catalyze the formation of a phosphodiester bond between the two segments of the new DNA strand, and it drops off. These unattached sections of the sugar-phosphate backbone in an otherwise full-replicated DNA strand are called nicks.
Once all the template nucleotides have been replicated, the replication process is not yet over. RNA primers need to be replaced with DNA, and nicks in the sugar-phosphate backbone need to be connected.
The group of cellular enzymes that remove RNA primers include the proteins FEN1 (flap endonulcease 1) and RNase H. The enzymes FEN1 and RNase H remove RNA primers at the start of each leading strand and at the start of each Okazaki fragment, leaving gaps of unreplicated template DNA. Once the primers are removed, a free-floating DNA polymerase lands at the 3′ end of the preceding DNA fragment and extends the DNA over the gap. However, this creates new nicks (unconnected sugar-phosphate backbone).
In the final stage of DNA replication, the enyzme ligase joins the sugar-phosphate backbones at each nick site. After ligase has connected all nicks, the new strand is one long continuous DNA strand, and the daughter DNA molecule is complete.
DNA Replication: This is a clip from a PBS production called “DNA: The Secret of Life.” It details the latest research (as of 2005) concerning the process of DNA replication. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/14%3A_DNA_Structure_and_Function/14.03%3A_DNA_Replication/14.3C%3A_DNA_Replication_in_Eukaryotes.txt |
As DNA polymerase alone cannot replicate the ends of chromosomes, telomerase aids in their replication and prevents chromosome degradation.
Learning Objectives
• Describe the role played by telomerase in replication of telomeres
Key Points
• DNA polymerase cannot replicate and repair DNA molecules at the ends of linear chromosomes.
• The ends of linear chromosomes, called telomeres, protect genes from getting deleted as cells continue to divide.
• The telomerase enzyme attaches to the end of the chromosome; complementary bases to the RNA template are added on the 3′ end of the DNA strand.
• Once the lagging strand is elongated by telomerase, DNA polymerase can add the complementary nucleotides to the ends of the chromosomes and the telomeres can finally be replicated.
• Cells that undergo cell division continue to have their telomeres shortened because most somatic cells do not make telomerase; telomere shortening is associated with aging.
• Telomerase reactivation in telomerase-deficient mice causes extension of telomeres; this may have potential for treating age-related diseases in humans.
Key Terms
• telomere: either of the repetitive nucleotide sequences at each end of a eukaryotic chromosome, which protect the chromosome from degradation
• telomerase: an enzyme in eukaryotic cells that adds a specific sequence of DNA to the telomeres of chromosomes after they divide, giving the chromosomes stability over time
The End Problem of Linear DNA Replication
Linear chromosomes have an end problem. After DNA replication, each newly synthesized DNA strand is shorter at its 5′ end than at the parental DNA strand’s 5′ end. This produces a 3′ overhang at one end (and one end only) of each daughter DNA strand, such that the two daughter DNAs have their 3′ overhangs at opposite ends
Every RNA primer synthesized during replication can be removed and replaced with DNA strands except the RNA primer at the 5′ end of the newly synthesized strand. This small section of RNA can only be removed, not replaced with DNA. Enzymes RNase H and FEN1 remove RNA primers, but DNA Polymerase will add new DNA only if the DNA Polymerase has an existing strand 5′ to it (“behind” it) to extend. However, there is no more DNA in the 5′ direction after the final RNA primer, so DNA polymerse cannot replace the RNA with DNA. Therefore, both daughter DNA strands have an incomplete 5′ strand with 3′ overhang.
In the absence of additional cellular processes, nucleases would digest these single-stranded 3′ overhangs. Each daughter DNA would become shorter than the parental DNA, and eventually entire DNA would be lost. To prevent this shortening, the ends of linear eukaryotic chromosomes have special structures called telomeres.
Telomere Replication
The ends of the linear chromosomes are known as telomeres: repetitive sequences that code for no particular gene. These telomeres protect the important genes from being deleted as cells divide and as DNA strands shorten during replication.
In humans, a six base pair sequence, TTAGGG, is repeated 100 to 1000 times. After each round of DNA replication, some telomeric sequences are lost at the 5′ end of the newly synthesized strand on each daughter DNA, but because these are noncoding sequences, their loss does not adversely affect the cell. However, even these sequences are not unlimited. After sufficient rounds of replication, all the telomeric repeats are lost, and the DNA risks losing coding sequences with subsequent rounds.
The discovery of the enzyme telomerase helped in the understanding of how chromosome ends are maintained. The telomerase enzyme attaches to the end of a chromosome and contains a catalytic part and a built-in RNA template. Telomerase adds complementary RNA bases to the 3′ end of the DNA strand. Once the 3′ end of the lagging strand template is sufficiently elongated, DNA polymerase adds the complementary nucleotides to the ends of the chromosomes; thus, the ends of the chromosomes are replicated.
Telomerase and Aging
Telomerase is typically active in germ cells and adult stem cells, but is not active in adult somatic cells. As a result, telomerase does not protect the DNA of adult somatic cells and their telomeres continually shorten as they undergo rounds of cell division.
In 2010, scientists found that telomerase can reverse some age-related conditions in mice. These findings may contribute to the future of regenerative medicine. In the studies, the scientists used telomerase-deficient mice with tissue atrophy, stem cell depletion, organ failure, and impaired tissue injury responses. Telomerase reactivation in these mice caused extension of telomeres, reduced DNA damage, reversed neurodegeneration, and improved the function of the testes, spleen, and intestines. Thus, telomere reactivation may have potential for treating age-related diseases in humans. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/14%3A_DNA_Structure_and_Function/14.03%3A_DNA_Replication/14.3D%3A_Telomere_Replication.txt |
Most mistakes during replication are corrected by DNA polymerase during replication or by post-replication repair mechanisms.
Learning Objectives
• Explain how errors during replication are repaired
Key Points
• Mismatch repair enzymes recognize mis-incorporated bases, remove them from DNA, and replace them with the correct bases.
• In nucleotide excision repair, enzymes remove incorrect bases with a few surrounding bases, which are replaced with the correct bases with the help of a DNA polymerase and the template DNA.
• When replication mistakes are not corrected, they may result in mutations, which sometimes can have serious consequences.
• Point mutations, one base substituted for another, can be silent (no effect) or may have effects ranging from mild to severe.
• Mutations may also involve insertions (addition of a base), deletion (loss of a base), or translocation (movement of a DNA section to a new location on the same or another chromosome ).
Key Terms
• mismatch repair: a system for recognizing and repairing some forms of DNA damage and erroneous insertion, deletion, or mis-incorporation of bases that can arise during DNA replication and recombination
• nucleotide excision repair: a DNA repair mechanism that corrects damage done by UV radiation, including thymine dimers and 6,4 photoproducts that cause bulky distortions in the DNA
Errors during Replication
DNA replication is a highly accurate process, but mistakes can occasionally occur as when a DNA polymerase inserts a wrong base. Uncorrected mistakes may sometimes lead to serious consequences, such as cancer. Repair mechanisms can correct the mistakes, but in rare cases mistakes are not corrected, leading to mutations; in other cases, repair enzymes are themselves mutated or defective.
Mutations: In this interactive, you can “edit” a DNA strand and cause a mutation. Take a look at the effects!
Most of the mistakes during DNA replication are promptly corrected by DNA polymerase which proofreads the base that has just been added. In proofreading, the DNA pol reads the newly-added base before adding the next one so a correction can be made. The polymerase checks whether the newly-added base has paired correctly with the base in the template strand. If it is the correct base, the next nucleotide is added. If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the incorrect nucleotide. This is performed by the exonuclease action of DNA pol III. Once the incorrect nucleotide has been removed, a new one will be added again.
Some errors are not corrected during replication, but are instead corrected after replication is completed; this type of repair is known as mismatch repair. The enzymes recognize the incorrectly-added nucleotide and excise it; this is then replaced by the correct base. If this remains uncorrected, it may lead to more permanent damage. How do mismatch repair enzymes recognize which of the two bases is the incorrect one? In E. coli, after replication, the nitrogenous base adenine acquires a methyl group; the parental DNA strand will have methyl groups, whereas the newly-synthesized strand lacks them. Thus, DNA polymerase is able to remove the incorrectly-incorporated bases from the newly-synthesized, non-methylated strand. In eukaryotes, the mechanism is not very well understood, but it is believed to involve recognition of unsealed nicks in the new strand, as well as a short-term continuing association of some of the replication proteins with the new daughter strand after replication has been completed.
In another type of repair mechanism, nucleotide excision repair, enzymes replace incorrect bases by making a cut on both the 3′ and 5′ ends of the incorrect base. The segment of DNA is removed and replaced with the correctly-paired nucleotides by the action of DNA pol. Once the bases are filled in, the remaining gap is sealed with a phosphodiester linkage catalyzed by DNA ligase. This repair mechanism is often employed when UV exposure causes the formation of pyrimidine dimers.
DNA Damage and Mutations
Errors during DNA replication are not the only reason why mutations arise in DNA. Mutations, variations in the nucleotide sequence of a genome, can also occur because of damage to DNA. Such mutations may be of two types: induced or spontaneous. Induced mutations are those that result from an exposure to chemicals, UV rays, X-rays, or some other environmental agent. Spontaneous mutations occur without any exposure to any environmental agent; they are a result of natural reactions taking place within the body.
Mutations may have a wide range of effects. Some mutations are not expressed; these are known as silent mutations. Point mutations are those mutations that affect a single base pair. The most common nucleotide mutations are substitutions, in which one base is replaced by another. These can be of two types: transitions or transversions. Transition substitution refers to a purine or pyrimidine being replaced by a base of the same kind; for example, a purine such as adenine may be replaced by the purine guanine. Transversion substitution refers to a purine being replaced by a pyrimidine or vice versa; for example, cytosine, a pyrimidine, is replaced by adenine, a purine. Mutations can also be the result of the addition of a base, known as an insertion, or the removal of a base, known as a deletion. Sometimes a piece of DNA from one chromosome may get translocated to another chromosome or to another region of the same chromosome. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/14%3A_DNA_Structure_and_Function/14.04%3A_DNA_Repair/14.4A%3A_DNA_Repair.txt |
Proteins, encoded by individual genes, orchestrate nearly every function of the cell.
Learning Objectives
• Describe transcription and translation
Key Points
• Genes are composed of DNA arranged on chromosomes.
• Some genes encode structural or regulatory RNAs. Other genes encode proteins.
• Replication copies DNA; transcription uses DNA to make complementary RNAs; translation uses mRNAs to make proteins.
• In eukaryotic cells, replication and transcription take place within the nucleus while translation takes place in the cytoplasm.
• In prokaryotic cells, replication, transcription, and translation occur in the cytoplasm.
Key Terms
• DNA: a biopolymer of deoxyribonucleic acids (a type of nucleic acid) that has four different chemical groups, called bases: adenine, guanine, cytosine, and thymine
• messenger RNA: Messenger RNA (mRNA) is a molecule of RNA that encodes a chemical “blueprint” for a protein product.
• protein: any of numerous large, complex naturally-produced molecules composed of one or more long chains of amino acids, in which the amino acid groups are held together by peptide bonds
Genes and Proteins
Since the rediscovery of Mendel’s work in 1900, the definition of the gene has progressed from an abstract unit of heredity to a tangible molecular entity capable of replication, transcription, translation, and mutation. Genes are composed of DNA and are linearly arranged on chromosomes. Some genes encode structural and regulatory RNAs. There is increasing evidence from research that profiles the transcriptome of cells (the complete set all RNA transcripts present in a cell) that these may be the largest classes of RNAs produced by eukaryotic cells, far outnumbering the protein-encoding messenger RNAs (mRNAs), but the 20,000 protein-encoding genes typically found in animal cells, and the 30,o00 protein-encoding genes typically found in plant cells, nonetheless have huge impacts on cellular functioning.
Protein-encoding genes specify the sequences of amino acids, which are the building blocks of proteins. In turn, proteins are responsible for orchestrating nearly every function of the cell. Both protein-encoding genes and the proteins that are their gene products are absolutely essential to life as we know it.
Replication, Transcription, and Translation are the three main processes used by all cells to maintain their genetic information and to convert the genetic information encoded in DNA into gene products, which are either RNAs or proteins, depending on the gene. In eukaryotic cells, or those cells that have a nucleus, replication and transcription take place within the nucleus while translation takes place outside of the nucleus in cytoplasm. In prokaryotic cells, or those cells that do not have a nucleus, all three processes occur in the cytoplasm.
Replication is the basis for biological inheritance. It copies a cell’s DNA. The enzyme DNA polymerase copies a single parental double-stranded DNA molecule into two daughter double-stranded DNA molecules. Transcription makes RNA from DNA. The enzyme RNA polymerase creates an RNA molecule that is complementary to a gene-encoding stretch of DNA. Translation makes protein from mRNA. The ribosome generates a polypeptide chain of amino acids using mRNA as a template. The polypeptide chain folds up to become a protein.
15.02: The Genetic Code - The Central Dogma- DNA Encodes RNA and RNA Encodes Protein
Learning Objectives
• Recall the central dogma of biology
The Genetic Code Is Degenerate and Universal
The genetic code is degenerate as there are 64 possible nucleotide triplets (43), which is far more than the number of amino acids. These nucleotide triplets are called codons; they instruct the addition of a specific amino acid to a polypeptide chain. Sixty-one of the codons encode twenty different amino acids. Most of these amino acids can be encoded by more than one codon. Three of the 64 codons terminate protein synthesis and release the polypeptide from the translation machinery. These triplets are called stop codons. The stop codon UGA is sometimes used to encode a 21st amino acid called selenocysteine (Sec), but only if the mRNA additionally contains a specific sequence of nucleotides called a selenocysteine insertion sequence (SECIS). The stop codon UAG is sometimes used by a few species of microorganisms to encode a 22nd amino acid called pyrrolysine (Pyl). The codon AUG, also has a special function. In addition to specifying the amino acid methionine, it also serves as the start codon to initiate translation. The reading frame for translation is set by the AUG start codon.
The genetic code is universal. With a few exceptions, virtually all species use the same genetic code for protein synthesis. The universal nature of the genetic code is powerful evidence that all of life on Earth shares a common origin.
The Central Dogma: DNA Encodes RNA, RNA Encodes Protein
The central dogma of molecular biology describes the flow of genetic information in cells from DNA to messenger RNA (mRNA) to protein. It states that genes specify the sequence of mRNA molecules, which in turn specify the sequence of proteins. Because the information stored in DNA is so central to cellular function, the cell keeps the DNA protected and copies it in the form of RNA. An enzyme adds one nucleotide to the mRNA strand for every nucleotide it reads in the DNA strand. The translation of this information to a protein is more complex because three mRNA nucleotides correspond to one amino acid in the polypeptide sequence.
Transcription: DNA to RNA
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that enzymes can convert back and forth from DNA to RNA. During transcription, a DNA sequence is read by RNA polymerase, which produces a complementary, antiparallel RNA strand. Unlike DNA replication, transcription results in an RNA complement that substitutes the RNA uracil (U) in all instances where the DNA thymine (T) would have occurred. Transcription is the first step in gene expression. The stretch of DNA transcribed into an RNA molecule is called a transcript. Some transcripts are used as structural or regulatory RNAs, and others encode one or more proteins. If the transcribed gene encodes a protein, the result of transcription is messenger RNA (mRNA), which will then be used to create that protein in the process of translation.
Translation: RNA to Protein
Translation is the process by which mRNA is decoded and translated to produce a polypeptide sequence, otherwise known as a protein. This method of synthesizing proteins is directed by the mRNA and accomplished with the help of a ribosome, a large complex of ribosomal RNAs (rRNAs) and proteins. In translation, a cell decodes the mRNA’s genetic message and assembles the brand-new polypeptide chain. Transfer RNA, or tRNA, translates the sequence of codons on the mRNA strand. The main function of tRNA is to transfer a free amino acid from the cytoplasm to a ribosome, where it is attached to the growing polypeptide chain. tRNAs continue to add amino acids to the growing end of the polypeptide chain until they reach a stop codon on the mRNA. The ribosome then releases the completed protein into the cell.
Interactive Element
DNA to protein: This interactive shows the process of DNA code being translated to a protein from start to finish!
Key Points
• The genetic code is degenerate because 64 codons encode only 22 amino acids.
• The genetic code is universal because it is the same among all organisms.
• Replication is the process of copying a molecule of DNA.
• Transcription is the process of converting a specific sequence of DNA into RNA.
• Translation is the process where a ribosome decodes mRNA into a protein.
Key Terms
• codon: a sequence of three adjacent nucleotides, which encode for a specific amino acid during protein synthesis or translation
• ribosome: protein/mRNA complexes found in all cells that are involved in the production of proteins by translating messenger RNA
• degenerate: the redundancy of the genetic code (more than one codon codes for each amino acid)
Contributions and Attributions
• OpenStax College, Biology. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44518/latest...ol11448/latest. License: CC BY: Attribution
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• OpenStax College, The Genetic Code. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44522/latest...e_15_01_02.jpg. License: CC BY: Attribution | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/15%3A_Genes_and_Proteins/15.01%3A_The_Genetic_Code_-_The_Relationship_Between_Genes_and_Proteins.txt |
The genetic code is a degenerate, non-overlapping set of 64 codons that encodes for 21 amino acids and 3 stop codons.
Learning Objectives
• Describe the genetic code and how the nucleotide sequence prescribes the amino acid and the protein sequence
Key Points
• The relationship between DNA base sequences and the amino acid sequence in proteins is called the genetic code.
• There are 61 codons that encode amino acids and 3 codons that code for chain termination for a total of 64 codons.
• Unlike, eukayrotes, a bacterial chromosome is a covalently-closed circle.
• The DNA double helix must partially unwind for transcription to occur; this unwound region is called a transcription bubble.
Key Terms
• nucleotide: the monomer comprising DNA or RNA molecules; consists of a nitrogenous heterocyclic base that can be a purine or pyrimidine, a five-carbon pentose sugar, and a phosphate group
• amino acid: Any of 20 naturally occurring α-amino acids (having the amino, and carboxylic acid groups on the same carbon atom), and a variety of side chains, that combine, via peptide bonds, to form proteins.
• redundancy: duplication of components, such as amino acid codons, to provide survival of the total system in case of failure of single components
The Genetic Code: Nucleotide sequences prescribe the amino acids
The genetic code is the relationship between DNA base sequences and the amino acid sequence in proteins. Features of the genetic code include:
• Amino acids are encoded by three nucleotides.
• It is non-overlapping.
• It is degenerate.
There are 21 genetically-encoded amino acids universally found in the species from all three domains of life. ( There is a 22nd genetically-encooded amino acid, Pyl, but so far it has only been found in a handful of Archaea and Bacteria species.) Yet there are only four different nucleotides in DNA or RNA, so a minimum of three nucleotides are needed to code each of the 21 (or 22) amino acids. The set of three nucleotides that codes for a single amino acid is known as a codon. There are 64 codons in total, 61 that encode amino acids and 3 that code for chain termination. Two of the codons for chain termination can, under certain circumstances, instead code for amino acids.
Degeneracy is the redundancy of the genetic code. The genetic code has redundancy, but no ambiguity. For example, although codons GAA and GAG both specify glutamic acid (redundancy), neither of them specifies any other amino acid (no ambiguity). The codons encoding one amino acid may differ in any of their three positions. For example, the amino acid glutamic acid is specified by GAA and GAG codons (difference in the third position); the amino acid leucine is specified by UUA, UUG, CUU, CUC, CUA, CUG codons (difference in the first or third position); while the amino acid serine is specified by UCA, UCG, UCC, UCU, AGU, AGC (difference in the first, second or third position). These properties of the genetic code make it more fault-tolerant for point mutations.
Origin of transcription on prokaryotic organisms
Prokaryotes are mostly single-celled organisms that, by definition, lack membrane-bound nuclei and other organelles. The central region of the cell in which prokaryotic DNA resides is called the nucleoid region. Bacterial and Archaeal chromosomes are covalently-closed circles that are not as extensively compacted as eukaryotic chromosomes, but are compacted nonetheless as the diameter of a typical prokaryotic chromosome is larger than the diameter of a typical prokaryotic cell. Additionally, prokaryotes often have abundant plasmids, which are shorter, circular DNA molecules that may only contain one or a few genes and often carry traits such as antibiotic resistance.
Transcription in prokaryotes (as in eukaryotes) requires the DNA double helix to partially unwind in the region of RNA synthesis. The region of unwinding is called a transcription bubble. Transcription always proceeds from the same DNA strand for each gene, which is called the template strand. The RNA product is complementary to the template strand and is almost identical to the other (non-template) DNA strand, called the sense or coding strand. The only difference is that in RNA all of the T nucleotides are replaced with U nucleotides.
The nucleotide on the DNA template strand that corresponds to the site from which the first 5′ RNA nucleotide is transcribed is called the +1 nucleotide, or the initiation site. Nucleotides preceding, or 5′ to, the template strand initiation site are given negative numbers and are designated upstream. Conversely, nucleotides following, or 3′ to, the template strand initiation site are denoted with “+” numbering and are called downstream nucleotides. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/15%3A_Genes_and_Proteins/15.03%3A_Prokaryotic_Transcription_-_Transcription_in_Prokaryotes.txt |
RNA polymerase initiates transcription at specific DNA sequences called promoters.
Learning Objectives
• Summarize the initial steps of transcription in prokaryotes
Key Points
• Transcription of mRNA begins at the initiation site.
• Two promoter consensus sequences are at the -10 and -35 regions upstream of the initiation site.
• The σ subunit of RNA polymerase recognizes and binds the -35 region.
• Five subunits (α, α, β, β’, and σ) make up the complete RNA polymerase holoenzyme.
Key Terms
• holoenzyme: a fully functioning enzyme, composed of all its subunits
• promoter: the section of DNA that controls the initiation of RNA transcription
Prokaryotic RNA Polymerase
Prokaryotes use the same RNA polymerase to transcribe all of their genes. In E. coli, the polymerase is composed of five polypeptide subunits, two of which are identical. Four of these subunits, denoted α, α, β, and β’, comprise the polymerase core enzyme. These subunits assemble each time a gene is transcribed; they disassemble once transcription is complete. Each subunit has a unique role: the two α-subunits are necessary to assemble the polymerase on the DNA; the β-subunit binds to the ribonucleoside triphosphate that will become part of the nascent “recently-born” mRNA molecule; and the β’ binds the DNA template strand. The fifth subunit, σ, is involved only in transcription initiation. It confers transcriptional specificity such that the polymerase begins to synthesize mRNA from an appropriate initiation site. Without σ, the core enzyme would transcribe from random sites and would produce mRNA molecules that specified protein gibberish. The polymerase comprised of all five subunits is called the holoenzyme.
Prokaryotic Promoters and Initiation of Transcription
The nucleotide pair in the DNA double helix that corresponds to the site from which the first 5′ mRNA nucleotide is transcribed is called the +1 site, or the initiation site. Nucleotides preceding the initiation site are given negative numbers and are designated upstream. Conversely, nucleotides following the initiation site are denoted with “+” numbering and are called downstream nucleotides.
A promoter is a DNA sequence onto which the transcription machinery binds and initiates transcription. In most cases, promoters exist upstream of the genes they regulate. The specific sequence of a promoter is very important because it determines whether the corresponding gene is transcribed all the time, some of the time, or infrequently. Although promoters vary among prokaryotic genomes, a few elements are conserved. At the -10 and -35 regions upstream of the initiation site, there are two promoter consensus sequences, or regions that are similar across all promoters and across various bacterial species. The -10 consensus sequence, called the -10 region, is TATAAT. The -35 sequence, TTGACA, is recognized and bound by σ. Once this interaction is made, the subunits of the core enzyme bind to the site. The A–T-rich -10 region facilitates unwinding of the DNA template; several phosphodiester bonds are made. The transcription initiation phase ends with the production of abortive transcripts, which are polymers of approximately 10 nucleotides that are made and released.
15.05: Prokaryotic Transcription - Elongation and Termination in Prokaryotes
Transcription elongation begins with the release of the polymerase σ subunit and terminates via the rho protein or via a stable hairpin.
Learning Objectives
• Explain the process of elongation and termination in prokaryotes
Key Points
• The transcription elongation phase begins with the dissociation of the σ subunit, which allows the core RNA polymerase enzyme to proceed along the DNA template.
• Rho-dependent termination is caused by the rho protein colliding with the stalled polymerase at a stretch of G nucleotides on the DNA template near the end of the gene.
• Rho-independent termination is caused the polymerase stalling at a stable hairpin formed by a region of complementary C–G nucleotides at the end of the mRNA.
Key Terms
• elongation: the addition of nucleotides to the 3′-end of a growing RNA chain during transcription
Elongation in Prokaryotes
The transcription elongation phase begins with the release of the σ subunit from the polymerase. The dissociation of σ allows the core RNA polymerase enzyme to proceed along the DNA template, synthesizing mRNA in the 5′ to 3′ direction at a rate of approximately 40 nucleotides per second. As elongation proceeds, the DNA is continuously unwound ahead of the core enzyme and rewound behind it. Since the base pairing between DNA and RNA is not stable enough to maintain the stability of the mRNA synthesis components, RNA polymerase acts as a stable linker between the DNA template and the nascent RNA strands to ensure that elongation is not interrupted prematurely.
Termination in Prokaryotes
Once a gene is transcribed, the prokaryotic polymerase needs to be instructed to dissociate from the DNA template and liberate the newly-made mRNA. Depending on the gene being transcribed, there are two kinds of termination signals: one is protein-based and the other is RNA-based.
Rho-dependent termination is controlled by the rho protein, which tracks along behind the polymerase on the growing mRNA chain. Near the end of the gene, the polymerase encounters a run of G nucleotides on the DNA template and it stalls. As a result, the rho protein collides with the polymerase. The interaction with rho releases the mRNA from the transcription bubble.
Rho-independent termination is controlled by specific sequences in the DNA template strand. As the polymerase nears the end of the gene being transcribed, it encounters a region rich in C–G nucleotides. The mRNA folds back on itself, and the complementary C–G nucleotides bind together. The result is a stable hairpin that causes the polymerase to stall as soon as it begins to transcribe a region rich in A–T nucleotides. The complementary U–A region of the mRNA transcript forms only a weak interaction with the template DNA. This, coupled with the stalled polymerase, induces enough instability for the core enzyme to break away and liberate the new mRNA transcript.
Upon termination, the process of transcription is complete. By the time termination occurs, the prokaryotic transcript would already have been used to begin synthesis of numerous copies of the encoded protein because these processes can occur concurrently in the cytoplasm. The unification of transcription, translation, and even mRNA degradation is possible because all of these processes occur in the same 5′ to 3′ direction and because there is no membranous compartmentalization in the prokaryotic cell. In contrast, the presence of a nucleus in eukaryotic cells prevents simultaneous transcription and translation. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/15%3A_Genes_and_Proteins/15.04%3A_Prokaryotic_Transcription_-_Initiation_of_Transcription_in_Prokaryotes.txt |
Learning Objectives
• Describe how transcription is initiated and proceeds along the DNA strand
Steps in Eukaryotic Transcription
Eukaryotic transcription is carried out in the nucleus of the cell by one of three RNA polymerases, depending on the RNA being transcribed, and proceeds in three sequential stages:
1. Initiation
2. Elongation
3. Termination.
Initiation of Transcription in Eukaryotes
Unlike the prokaryotic RNA polymerase that can bind to a DNA template on its own, eukaryotes require several other proteins, called transcription factors, to first bind to the promoter region and then help recruit the appropriate polymerase. The completed assembly of transcription factors and RNA polymerase bind to the promoter, forming a transcription pre-initiation complex (PIC).
The most-extensively studied core promoter element in eukaryotes is a short DNA sequence known as a TATA box, found 25-30 base pairs upstream from the start site of transcription. Only about 10-15% of mammalian genes contain TATA boxes, while the rest contain other core promoter elements, but the mechanisms by which transcription is initiated at promoters with TATA boxes is well characterized.
The TATA box, as a core promoter element, is the binding site for a transcription factor known as TATA-binding protein (TBP), which is itself a subunit of another transcription factor: Transcription Factor II D (TFIID). After TFIID binds to the TATA box via the TBP, five more transcription factors and RNA polymerase combine around the TATA box in a series of stages to form a pre-initiation complex. One transcription factor, Transcription Factor II H (TFIIH), is involved in separating opposing strands of double-stranded DNA to provide the RNA Polymerase access to a single-stranded DNA template. However, only a low, or basal, rate of transcription is driven by the pre-initiation complex alone. Other proteins known as activators and repressors, along with any associated coactivators or corepressors, are responsible for modulating transcription rate. Activator proteins increase the transcription rate, and repressor proteins decrease the transcription rate.
The Three Eukaryotic RNA Polymerases (RNAPs)
The features of eukaryotic mRNA synthesis are markedly more complex those of prokaryotes. Instead of a single polymerase comprising five subunits, the eukaryotes have three polymerases that are each made up of 10 subunits or more. Each eukaryotic polymerase also requires a distinct set of transcription factors to bring it to the DNA template.
RNA polymerase I is located in the nucleolus, a specialized nuclear substructure in which ribosomal RNA (rRNA) is transcribed, processed, and assembled into ribosomes. The rRNA molecules are considered structural RNAs because they have a cellular role but are not translated into protein. The rRNAs are components of the ribosome and are essential to the process of translation. RNA polymerase I synthesizes all of the rRNAs except for the 5S rRNA molecule.
RNA polymerase II is located in the nucleus and synthesizes all protein-coding nuclear pre-mRNAs. Eukaryotic pre-mRNAs undergo extensive processing after transcription, but before translation. RNA polymerase II is responsible for transcribing the overwhelming majority of eukaryotic genes, including all of the protein-encoding genes which ultimately are translated into proteins and genes for several types of regulatory RNAs, including microRNAs (miRNAs) and long-coding RNAs (lncRNAs).
RNA polymerase III is also located in the nucleus. This polymerase transcribes a variety of structural RNAs that includes the 5S pre-rRNA, transfer pre-RNAs (pre-tRNAs), and small nuclear pre-RNAs. The tRNAs have a critical role in translation: they serve as the adaptor molecules between the mRNA template and the growing polypeptide chain. Small nuclear RNAs have a variety of functions, including “splicing” pre-mRNAs and regulating transcription factors. Not all miRNAs are transcribed by RNA Polymerase II, RNA Polymerase III transcribes some of them.
Interactive Element
Modeling transcription: This interactive models the process of DNA transcription in a eukaryotic cell.
Key Points
• Eukaryotic transcription is carried out in the nucleus of the cell and proceeds in three sequential stages: initiation, elongation, and termination.
• Eukaryotes require transcription factors to first bind to the promoter region and then help recruit the appropriate polymerase.
• RNA Polymerase II is the polymerase responsible for transcribing mRNA.
Key Terms
• repressor: any protein that binds to DNA and thus regulates the expression of genes by decreasing the rate of transcription
• activator: any chemical or agent which regulates one or more genes by increasing the rate of transcription
• polymerase: any of various enzymes that catalyze the formation of polymers of DNA or RNA using an existing strand of DNA or RNA as a template | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/15%3A_Genes_and_Proteins/15.06%3A_Eukaryotic_Transcription_-_Initiation_of_Transcription_in_Eukaryotes.txt |
Elongation synthesizes pre-mRNA in a 5′ to 3′ direction, and termination occurs in response to termination sequences and signals.
Learning Objectives
• Describe what is happening during transcription elongation and termination
Key Points
• RNA polymerase II (RNAPII) transcribes the major share of eukaryotic genes.
• During elongation, the transcription machinery needs to move histones out of the way every time it encounters a nucleosome.
• Transcription elongation occurs in a bubble of unwound DNA, where the RNA Polymerase uses one strand of DNA as a template to catalyze the synthesis of a new RNA strand in the 5′ to 3′ direction.
• RNA Polymerase I and RNA Polymerase III terminate transcription in response to specific termination sequences in either the DNA being transcribed (RNA Polymerase I) or in the newly-synthesized RNA (RNA Polymerase III).
• RNA Polymerase II terminates transcription at random locations past the end of the gene being transcribed. The newly-synthesized RNA is cleaved at a sequence-specified location and released before transcription terminates.
Key Terms
• nucleosome: any of the subunits that repeat in chromatin; a coil of DNA surrounding a histone core
• histone: any of various simple water-soluble proteins that are rich in the basic amino acids lysine and arginine and are complexed with DNA in the nucleosomes of eukaryotic chromatin
• chromatin: a complex of DNA, RNA, and proteins within the cell nucleus out of which chromosomes condense during cell division
Transcription through Nucleosomes
Following the formation of the pre-initiation complex, the polymerase is released from the other transcription factors, and elongation is allowed to proceed with the polymerase synthesizing RNA in the 5′ to 3′ direction. RNA Polymerase II (RNAPII) transcribes the major share of eukaryotic genes, so this section will mainly focus on how this specific polymerase accomplishes elongation and termination.
Although the enzymatic process of elongation is essentially the same in eukaryotes and prokaryotes, the eukaryotic DNA template is more complex. When eukaryotic cells are not dividing, their genes exist as a diffuse, but still extensively packaged and compacted mass of DNA and proteins called chromatin. The DNA is tightly packaged around charged histone proteins at repeated intervals. These DNA–histone complexes, collectively called nucleosomes, are regularly spaced and include 146 nucleotides of DNA wound twice around the eight histones in a nucleosome like thread around a spool.
For polynucleotide synthesis to occur, the transcription machinery needs to move histones out of the way every time it encounters a nucleosome. This is accomplished by a special protein dimer called FACT, which stands for “facilitates chromatin transcription.” FACT partially disassembles the nucleosome immediately ahead (upstream) of a transcribing RNA Polymerase II by removing two of the eight histones (a single dimer of H2A and H2B histones is removed.) This presumably sufficiently loosens the DNA wrapped around that nucleosome so that RNA Polymerase II can transcribe through it. FACT reassembles the nucleosome behind the RNA Polymerase II by returning the missing histones to it. RNA Polymerase II will continue to elongate the newly-synthesized RNA until transcription terminates.
Elongation
RNA Polymerase II is a complex of 12 protein subunits. Specific subunits within the protein allow RNA Polymerase II to act as its own helicase, sliding clamp, single-stranded DNA binding protein, as well as carry out other functions. Consequently, RNA Polymerase II does not need as many accessory proteins to catalyze the synthesis of new RNA strands during transcription elongation as DNA Polymerase does to catalyze the synthesis of new DNA strands during replication elongation.
However, RNA Polymerase II does need a large collection of accessory proteins to initiate transcription at gene promoters, but once the double-stranded DNA in the transcription start region has been unwound, the RNA Polymerase II has been positioned at the +1 initiation nucleotide, and has started catalyzing new RNA strand synthesis, RNA Polymerase II clears or “escapes” the promoter region and leaves most of the transcription initiation proteins behind.
All RNA Polymerases travel along the template DNA strand in the 3′ to 5′ direction and catalyze the synthesis of new RNA strands in the 5′ to 3′ direction, adding new nucleotides to the 3′ end of the growing RNA strand.
RNA Polymerases unwind the double stranded DNA ahead of them and allow the unwound DNA behind them to rewind. As a result, RNA strand synthesis occurs in a transcription bubble of about 25 unwound DNA basebairs. Only about 8 nucleotides of newly-synthesized RNA remain basepaired to the template DNA. The rest of the RNA molecules falls off the template to allow the DNA behind it to rewind.
RNA Polymerases use the DNA strand below them as a template to direct which nucleotide to add to the 3′ end of the growing RNA strand at each point in the sequence. The RNA Polymerase travels along the template DNA one nucleotide at at time. Whichever RNA nucleotide is capable of basepairing to the template nucleotide below the RNA Polymerase is the next nucleotide to be added. Once the addition of a new nucleotide to the 3′ end of the growing strand has been catalyzed, the RNA Polymerase moves to the next DNA nucleotide on the template below it. This process continues until transcription termination occurs.
Termination
The termination of transcription is different for the three different eukaryotic RNA polymerases.
The ribosomal rRNA genes transcribed by RNA Polymerase I contain a specific sequence of basepairs (11 bp long in humans; 18 bp in mice) that is recognized by a termination protein called TTF-1 (Transcription Termination Factor for RNA Polymerase I.) This protein binds the DNA at its recognition sequence and blocks further transcription, causing the RNA Polymerase I to disengage from the template DNA strand and to release its newly-synthesized RNA.
The protein-encoding, structural RNA, and regulatory RNA genes transcribed by RNA Polymerse II lack any specific signals or sequences that direct RNA Polymerase II to terminate at specific locations. RNA Polymerase II can continue to transcribe RNA anywhere from a few bp to thousands of bp past the actual end of the gene. However, the transcript is cleaved at an internal site before RNA Polymerase II finishes transcribing. This releases the upstream portion of the transcript, which will serve as the initial RNA prior to further processing (the pre-mRNA in the case of protein-encoding genes.) This cleavage site is considered the “end” of the gene. The remainder of the transcript is digested by a 5′-exonuclease (called Xrn2 in humans) while it is still being transcribed by the RNA Polymerase II. When the 5′-exonulease “catches up” to RNA Polymerase II by digesting away all the overhanging RNA, it helps disengage the polymerase from its DNA template strand, finally terminating that round of transcription.
In the case of protein-encoding genes, the cleavage site which determines the “end” of the emerging pre-mRNA occurs between an upstream AAUAAA sequence and a downstream GU-rich sequence separated by about 40-60 nucleotides in the emerging RNA. Once both of these sequences have been transcribed, a protein called CPSF in humans binds the AAUAAA sequence and a protein called CstF in humans binds the GU-rich sequence. These two proteins form the base of a complicated protein complex that forms in this region before CPSF cleaves the nascent pre-mRNA at a site 10-30 nucleotides downstream from the AAUAAA site. The Poly(A) Polymerase enzyme which catalyzes the addition of a 3′ poly-A tail on the pre-mRNA is part of the complex that forms with CPSF and CstF.
The tRNA, 5S rRNA, and structural RNAs genes transcribed by RNA Polymerase III have a not-entirely-understood termination signal. The RNAs transcribed by RNA Polymerase III have a short stretch of four to seven U’s at their 3′ end. This somehow triggers RNA Polymerase III to both release the nascent RNA and disengage from the template DNA strand.
Contributions and Attributions
• An Introduction to Molecular Biology/Transcription of RNA and its modification. Provided by: Wikibooks. Located at: en.wikibooks.org/wiki/An_Intr...s_modification. License: CC BY-SA: Attribution-ShareAlike
• OpenStax College, Biology. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44524/latest...ol11448/latest. License: CC BY: Attribution
• Structural Biochemistry/Transcription. Provided by: Wikibooks. Located at: en.wikibooks.org/wiki/Structu...RNA_Polymerase. License: CC BY-SA: Attribution-ShareAlike
• Eukaryotic transcription. Provided by: Wikipedia. Located at: en.Wikipedia.org/wiki/Eukaryo...n%23Initiation. License: CC BY-SA: Attribution-ShareAlike
• repressor. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/repressor. License: CC BY-SA: Attribution-ShareAlike
• polymerase. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/polymerase. License: CC BY-SA: Attribution-ShareAlike
• activator. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/activator. License: CC BY-SA: Attribution-ShareAlike
• OpenStax College, Eukaryotic Transcription October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44524/latest...e_15_03_01.jpg. License: CC BY: Attribution
• OpenStax College, Biology. October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44524/latest...ol11448/latest. License: CC BY: Attribution
• chromatin. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/chromatin. License: CC BY-SA: Attribution-ShareAlike
• histone. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/histone. License: CC BY-SA: Attribution-ShareAlike
• nucleosome. Provided by: Wiktionary. Located at: en.wiktionary.org/wiki/nucleosome. License: CC BY-SA: Attribution-ShareAlike
• OpenStax College, Eukaryotic Transcription October 16, 2013. Provided by: OpenStax CNX. Located at: http://cnx.org/content/m44524/latest...e_15_03_01.jpg. License: CC BY: Attribution | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/15%3A_Genes_and_Proteins/15.07%3A_Eukaryotic_Transcription_-_Elongation_and_Termination_in_Eukaryotes.txt |
Eukaryotic pre-mRNA receives a 5′ cap and a 3′ poly (A) tail before introns are removed and the mRNA is considered ready for translation.
Learning Objectives
• Outline the steps of pre-mRNA processing
Key Points
• A 7-methylguanosine cap is added to the 5′ end of the pre-mRNA while elongation is still in progress. The 5′ cap protects the nascent mRNA from degradation and assists in ribosome binding during translation.
• A poly (A) tail is added to the 3′ end of the pre-mRNA once elongation is complete. The poly (A) tail protects the mRNA from degradation, aids in the export of the mature mRNA to the cytoplasm, and is involved in binding proteins involved in initiating translation.
• Introns are removed from the pre-mRNA before the mRNA is exported to the cytoplasm.
Key Terms
• intron: a portion of a split gene that is included in pre-RNA transcripts but is removed during RNA processing and rapidly degraded
• moiety: a specific segment of a molecule
• spliceosome: a dynamic complex of RNA and protein subunits that removes introns from precursor mRNA
Pre-mRNA Processing
The eukaryotic pre-mRNA undergoes extensive processing before it is ready to be translated. The additional steps involved in eukaryotic mRNA maturation create a molecule with a much longer half-life than a prokaryotic mRNA. Eukaryotic mRNAs last for several hours, whereas the typical E. coli mRNA lasts no more than five seconds.
Pre-mRNAs are first coated in RNA-stabilizing proteins; these protect the pre-mRNA from degradation while it is processed and exported out of the nucleus. The three most important steps of pre-mRNA processing are the addition of stabilizing and signaling factors at the 5′ and 3′ ends of the molecule, and the removal of intervening sequences that do not specify the appropriate amino acids. In rare cases, the mRNA transcript can be “edited” after it is transcribed.
5′ Capping
While the pre-mRNA is still being synthesized, a 7-methylguanosine cap is added to the 5′ end of the growing transcript by a 5′-to-5′ phosphate linkage. This moiety protects the nascent mRNA from degradation. In addition, initiation factors involved in protein synthesis recognize the cap to help initiate translation by ribosomes.
3′ Poly-A Tail
While RNA Polymerase II is still transcribing downstream of the proper end of a gene, the pre-mRNA is cleaved by an endonuclease-containing protein complex between an AAUAAA consensus sequence and a GU-rich sequence. This releases the functional pre-mRNA from the rest of the transcript, which is still attached to the RNA Polymerase. An enzyme called poly (A) polymerase (PAP) is part of the same protein complex that cleaves the pre-mRNA and it immediately adds a string of approximately 200 A nucleotides, called the poly (A) tail, to the 3′ end of the just-cleaved pre-mRNA. The poly (A) tail protects the mRNA from degradation, aids in the export of the mature mRNA to the cytoplasm, and is involved in binding proteins involved in initiating translation.
Pre-mRNA Splicing
Eukaryotic genes are composed of exons, which correspond to protein-coding sequences (ex-on signifies that they are expressed), and intervening sequences called introns (int-ron denotes their intervening role), which may be involved in gene regulation, but are removed from the pre-mRNA during processing. Intron sequences in mRNA do not encode functional proteins.
Discovery of Introns
The discovery of introns came as a surprise to researchers in the 1970s who expected that pre-mRNAs would specify protein sequences without further processing, as they had observed in prokaryotes. The genes of higher eukaryotes very often contain one or more introns. While these regions may correspond to regulatory sequences, the biological significance of having many introns or having very long introns in a gene is unclear. It is possible that introns slow down gene expression because it takes longer to transcribe pre-mRNAs with lots of introns. Alternatively, introns may be nonfunctional sequence remnants left over from the fusion of ancient genes throughout evolution. This is supported by the fact that separate exons often encode separate protein subunits or domains. For the most part, the sequences of introns can be mutated without ultimately affecting the protein product.
Intron Processing
All introns in a pre-mRNA must be completely and precisely removed before protein synthesis. If the process errs by even a single nucleotide, the reading frame of the rejoined exons would shift, and the resulting protein would be dysfunctional. The process of removing introns and reconnecting exons is called splicing. Introns are removed and degraded while the pre-mRNA is still in the nucleus. Splicing occurs by a sequence-specific mechanism that ensures introns will be removed and exons rejoined with the accuracy and precision of a single nucleotide. The splicing of pre-mRNAs is conducted by complexes of proteins and RNA molecules called spliceosomes.
Each spliceosome is composed of five subunits called snRNPs (for small nuclear ribonucleoparticles, and pronounced “snurps”.) Each snRNP is itself a complex of proteins and a special type of RNA found only in the nucleus called snRNAs (small nuclear RNAs). Spliceosomes recognize sequences at the 5′ end of the intron because introns always start with the nucleotides GU and they recognize sequences at the 3′ end of the intron because they always end with the nucleotides AG. The spliceosome cleaves the pre-mRNA’s sugar phosphate backbone at the G that starts the intron and then covalently attaches that G to an internal A nucleotide within the intron. Then the spliceosme connects the 3′ end of the first exon to the 5′ end of the following exon, cleaving the 3′ end of the intron in the process. This results in the splicing together of the two exons and the release of the intron in a lariat form. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/15%3A_Genes_and_Proteins/15.08%3A__RNA_Processing_in_Eukaryotes_-_mRNA_Processing.txt |
rRNA and tRNA are structural molecules that aid in protein synthesis but are not themselves translated into protein.
Learning Objectives
• Describe how pre-rRNAs and pre-tRNAs are processed into mature rRNAs and tRNAs.
Key Points
• Ribosomal RNA (rRNA) is a structural molecule that makes up over half of the mass of a ribosome and aids in protein synthesis.
• Transfer RNA (tRNA) recognizes a codon on mRNA and brings the appropriate amino acid to that site.
• rRNAs are processed from larger pre-rRNAs by trimming the larger rRNAs down and methylating some of the nucleotides.
• tRNAs are processed from pre-tRNAs by trimming both ends of the pre-tRNA, adding a CCA trinucleotide to the 3′ end, if needed, removing any introns present, and chemically modified 12 nucleotides on average per tRNA.
Key Terms
• anticodon: a sequence of three nucleotides in transfer RNA that binds to the complementary triplet (codon) in messenger RNA, specifying an amino acid during protein synthesis
Processing of tRNAs and rRNAs
The tRNAs and rRNAs are structural molecules that have roles in protein synthesis; however, these RNAs are not themselves translated. In eukaryotes, pre-rRNAs are transcribed, processed, and assembled into ribosomes in the nucleolus, while pre-tRNAs are transcribed and processed in the nucleus and then released into the cytoplasm where they are linked to free amino acids for protein synthesis.
Ribosomal RNA (rRNA)
The four rRNAs in eukaryotes are first transcribed as two long precursor molecules. One contains just the pre-rRNA that will be processed into the 5S rRNA; the other spans the 28S, 5.8S, and 18S rRNAs. Enzymes then cleave the precursors into subunits corresponding to each rRNA. In bacteria, there are only three rRNAs and all are transcribed in one long precursor molecule that is cleaved into the individual rRNAs. Some of the bases of pre-rRNAs are methylated for added stability. Mature rRNAs make up 50-60% of each ribosome. Some of a ribosome’s RNA molecules are purely structural, whereas others have catalytic or binding activities.
The eukaryotic ribosome is composed of two subunits: a large subunit (60S) and a small subunit (40S). The 60S subunit is composed of the 28S rRNA, 5.8S rRNA, 5S rRNA, and 50 proteins. The 40S subunit is composed of the 18S rRNA and 33 proteins. The bacterial ribosome is composed of two similar subunits, with slightly different components. The bacterial large subunit is called the 50S subunit and is composed of the 23S rRNA, 5S rRNA, and 31 proteins, while the bacterial small subunit is called the 30S subunit and is composed of the 16S rRNA and 21 proteins.
The two subunits join to constitute a functioning ribosome that is capable of creating proteins.
Transfer RNA (tRNA)
Each different tRNA binds to a specific amino acid and transfers it to the ribosome. Mature tRNAs take on a three-dimensional structure through intramolecular basepairing to position the amino acid binding site at one end and the anticodon in an unbasepaired loop of nucleotides at the other end. The anticodon is a three-nucleotide sequence, unique to each different tRNA, that interacts with a messenger RNA (mRNA) codon through complementary base pairing.
There are different tRNAs for the 21 different amino acids. Most amino acids can be carried by more than one tRNA.
In all organisms, tRNAs are transcribed in a pre-tRNA form that requires multiple processing steps before the mature tRNA is ready for use in translation. In bacteria, multiple tRNAs are often transcribed as a single RNA. The first step in their processing is the digestion of the RNA to release individual pre-tRNAs. In archaea and eukaryotes, each pre-tRNA is transcribed as a separate transcript.
The processing to convert the pre-tRNA to a mature tRNA involves five steps.
1. The 5′ end of the pre-tRNA, called the 5′ leader sequence, is cleaved off.
2. The 3′ end of the pre-tRNA is cleaved off.
3. In all eukaryote pre-tRNAs, but in only some bacterial and archaeal pre-tRNAs, a CCA sequence of nucleotides is added to the 3′ end of the pre-tRNA after the original 3′ end is trimmed off. Some bacteria and archaea pre-tRNAs already have the CCA encoded in their transcript immediately upstream of the 3′ cleavage site, so they don’t need to add one. The CCA at the 3′ end of the mature tRNA will be the site at which the tRNA’s amino acid will be added.
4. Multiple nucleotides in the pre-tRNA are chemically modified, altering their nitorgen bases. On average about 12 nucleotides are modified per tRNA. The most common modifications are the conversion of adenine (A) to pseudouridine (ψ), the conversion of adenine to inosine (I), and the conversion of uridine to dihydrouridine (D). But over 100 other modifications can occur.
5. A significant number of eukaryotic and archaeal pre-tRNAs have introns that have to be spliced out. Introns are rarer in bacterial pre-tRNAs, but do occur occasionally and are spliced out.
After processing, the mature pre-tRNA is ready to have its cognate amino acid attached. The cognate amino acid for a tRNA is the one specified by its anticodon. Attaching this amino acid is called charging the tRNA. In eukaryotes, the mature tRNA is generated in the nucleus, and then exported to the cytoplasm for charging. | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/15%3A_Genes_and_Proteins/15.09%3A_RNA_Processing_in_Eukaryotes_-_Processing_of_tRNAs_and_rRNAs.txt |
Protein synthesis, or translation of mRNA into protein, occurs with the help of ribosomes, tRNAs, and aminoacyl tRNA synthetases.
Learning Objectives
• Explain the role played by ribosomes, tRNA, and aminoacyl tRNA synthetases in protein synthesis
Key Points
• Ribosomes, macromolecular structures composed of rRNA and polypeptide chains, are formed of two subunits (in bacteria and archaea, 30S and 50S; in eukaryotes, 40S and 60S), that bring together mRNA and tRNAs to catalyze protein synthesis.
• Fully assembled ribosomes have three tRNA binding sites: an A site for incoming aminoacyl-tRNAs, a P site for peptidyl-tRNAs, and an E site where empty tRNAs exit.
• tRNAs (transfer ribonucleic acids), which serve to deliver the appropriate amino acid to the growing peptide chain, consist of a modified RNA chain with the appropriate amino acid covalently attached.
• tRNAs have a loop of unbasepaired nucleotides at one end of the molecule that contains three nucleotides that act as the anticodon that basepairs to the mRNA codon.
• Aminoacyl tRNA synthetases are enzymes that load the individual amino acids onto the tRNAs.
Key Terms
• ribosome: protein/mRNA complexes found in all cells that are involved in the production of proteins by translating messenger RNA
The Protein Synthesis Machinery
In addition to the mRNA template, many molecules and macromolecules contribute to the process of translation. The composition of each component may vary across species. For instance, ribosomes may consist of different numbers of rRNAs and polypeptides depending on the organism. However, the general structures and functions of the protein synthesis machinery are comparable from bacteria to archaea to human cells. Translation requires the input of an mRNA template, ribosomes, tRNAs, and various enzymatic factors.
Ribosomes
A ribosome is a complex macromolecule composed of structural and catalytic rRNAs, and many distinct polypeptides. In eukaryotes, the synthesis and assembly of rRNAs occurs in the nucleolus.
Ribosomes exist in the cytoplasm in prokaryotes and in the cytoplasm and on rough endoplasmic reticulum membranes in eukaryotes. Mitochondria and chloroplasts also have their own ribosomes, and these look more similar to prokaryotic ribosomes (and have similar drug sensitivities) than the cytoplasmic ribosomes. Ribosomes dissociate into large and small subunits when they are not synthesizing proteins and reassociate during the initiation of translation.E. coli have a 30S small subunit and a 50S large subunit, for a total of 70S when assembled (recall that Svedberg units are not additive). Mammalian ribosomes have a small 40S subunit and a large 60S subunit, for a total of 80S. The small subunit is responsible for binding the mRNA template, whereas the large subunit sequentially binds tRNAs.
In bacteria, archaea, and eukaryotes, the intact ribosome has three binding sites that accomodate tRNAs: The A site, the P site, and the E site. Incoming aminoacy-tRNAs (a tRNA with an amino acid covalently attached is called an aminoacyl-tRNA) enter the ribosome at the A site. The peptidyl-tRNA carrying the growing polypeptide chain is held in the P site. The E site holds empty tRNAs just before they exit the ribosome.
Each mRNA molecule is simultaneously translated by many ribosomes, all reading the mRNA from 5′ to 3′ and synthesizing the polypeptide from the N terminus to the C terminus. The complete mRNA/poly-ribosome structure is called a polysome.
tRNAs in eukaryotes
The tRNA molecules are transcribed by RNA polymerase III. Depending on the species, 40 to 60 types of tRNAs exist in the cytoplasm. Specific tRNAs bind to codons on the mRNA template and add the corresponding amino acid to the polypeptide chain. (More accurately, the growing polypeptide chain is added to each new amino acid bound in by a tRNA.)
The transfer RNAs (tRNAs) are structural RNA molecules. In eukaryotes, tRNA mole are transcribed from tRNA genes by RNA polymerase III. Depending on the species, 40 to 60 types of tRNAs exist in the cytoplasm. Serving as adaptors, specific tRNAs bind to sequences on the mRNA template and add the corresponding amino acid to the polypeptide chain. (More accurately, the growing polypeptide chain is added to each new amino acid brought in by a tRNA.) Therefore, tRNAs are the molecules that actually “translate” the language of RNA into the language of proteins.
Of the 64 possible mRNA codons (triplet combinations of A, U, G, and C) three specify the termination of protein synthesis and 61 specify the addition of amino acids to the polypeptide chain. Of the three termination codons, one (UGA) can also be used to encode the 21st amino acid, selenocysteine, but only if the mRNA contains a specific sequence of nucleotides known as a SECIS sequence. Of the 61 non-termination codons, one codon (AUG) also encodes the initiation of translation.
Each tRNA polynucleotide chain folds up so that some internal sections basepair with other internal sections. If just diagrammed in two dimensions, the regions where basepairing occurs are called stems, and the regions where no basepairs form are called loops, and the entire pattern of stems and loops that forms for a tRNA is called the “cloverleaf” structure. All tRNAs fold into very similar cloverleaf structures of four major stems and three major loops.
If viewed as a three-dimensional structure, all the basepaired regions of the tRNA are helical, and the tRNA folds into a L-shaped structure.
Each tRNA has a sequence of three nucleotides located in a loop at one end of the molecule that can basepair with an mRNA codon. This is called the tRNA’s anticodon. Each different tRNA has a different anticodon. When the tRNA anticodon basepairs with one of the mRNA codons, the tRNA will add an amino acid to a growing polypeptide chain or terminate translation, according to the genetic code. For instance, if the sequence CUA occurred on a mRNA template in the proper reading frame, it would bind a tRNA with an anticodon expressing the complementary sequence, GAU. The tRNA with this anticodon would be linked to the amino acid leucine.
Aminoacyl tRNA Synthetases
The process of pre-tRNA synthesis by RNA polymerase III only creates the RNA portion of the adaptor molecule. The corresponding amino acid must be added later, once the tRNA is processed and exported to the cytoplasm. Through the process of tRNA “charging,” each tRNA molecule is linked to its correct amino acid by a group of enzymes called aminoacyl tRNA synthetases. When an amino acid is covalently linked to a tRNA, the resulting complex is known as an aminoacyl-tRNA. At least one type of aminoacyl tRNA synthetase exists for each of the 21 amino acids; the exact number of aminoacyl tRNA synthetases varies by species. These enzymes first bind and hydrolyze ATP to catalyze the formation of a covalent bond between an amino acid and adenosine monophosphate (AMP); a pyrophosphate molecule is expelled in this reaction. This is called “activating” the amino acid. The same enzyme then catalyzes the attachment of the activated amino acid to the tRNA and the simultaneous release of AMP. After the correct amino acid covalently attached to the tRNA, it is released by the enzyme. The tRNA is said to be charged with its cognate amino acid. (the amino acid specified by its anticodon is a tRNA’s cognate amino acid.) | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/15%3A_Genes_and_Proteins/15.10%3A__Ribosomes_and_Protein_Synthesis_-_The_Protein_Synthesis_Machinery.txt |
Learning Objectives
• Describe the process of translation
As with mRNA synthesis, protein synthesis can be divided into three phases: initiation, elongation, and termination.
Initiation of Translation
Protein synthesis begins with the formation of a pre-initiation complex. In E. coli, this complex involves the small 30S ribosome, the mRNA template, three initiation factors (IFs; IF-1, IF-2, and IF-3), and a special initiator tRNA, called fMet-tRNA. The initiator tRNA basepairs to the start codon AUG (or rarely, GUG) and is covalently linked to a formylated methionine called fMet. Methionine is one of the 21 amino acids used in protein synthesis; formylated methionine is a methione to which a formyl group (a one-carbon aldehyde) has been covalently attached at the amino nitrogen. Formylated methionine is inserted by fMet-tRNA at the beginning of every polypeptide chain synthesized by E. coli, and is usually clipped off after translation is complete. When an in-frame AUG is encountered during translation elongation, a non-formylated methionine is inserted by a regular Met-tRNA. In E. coli mRNA, a sequence upstream of the first AUG codon, called the Shine-Dalgarno sequence (AGGAGG), interacts with the rRNA molecules that compose the ribosome. This interaction anchors the 30S ribosomal subunit at the correct location on the mRNA template.
In eukaryotes, a pre-initiation complex forms when an initiation factor called eIF2 ( eukaryotic initiation factor 2) binds GTP, and the GTP-eIF2 recruits the eukaryotic initiator tRNA to the 40s small ribosomal subunit. The initiator tRNA, called Met-tRNAi, carries unmodified methionine in eukaryotes, not fMet, but it is distinct from other cellular Met-tRNAs in that it can bind eIFs and it can bind at the ribosome P site. The eukaryotic pre-initiation complex then recognizes the 7-methylguanosine cap at the 5′ end of a mRNA. Several other eIFs, specifically eIF1, eIF3, and eIF4, act as cap-binding proteins and assist the recruitment of the pre-initiation complex to the 5′ cap. Poly (A)-Binding Protein (PAB) binds both the poly (A) tail of the mRNA and the complex of proteins at the cap and also assists in the process. Once at the cap, the pre-initiation complex tracks along the mRNA in the 5′ to 3′ direction, searching for the AUG start codon. Many, but not all, eukaryotic mRNAs are translated from the first AUG sequence. The nucleotides around the AUG indicate whether it is the correct start codon.
Once the appropriate AUG is identified, eIF2 hydrolyzes GTP to GDP and powers the delivery of the tRNAi-Met to the start codon, where the tRNAi anticodon basepairs to the AUG codon. After this, eIF2-GDP is released from the complex, and eIF5-GTP binds. The 60S ribosomal subunit is recruited to the pre-initiation complex by eIF5-GTP, which hydrolyzes its GTP to GDP to power the assembly of the full ribosome at the translation start site with the Met-tRNAi positioned in the ribosome P site. The remaining eIFs dissociate from the ribosome and translation is ready to begins.
In archaea, translation initiation is similar to that seen in eukaryotes, except that the initiation factors involved are called aIFs (archaeal inititiaion factors), not eIFs.
Translation Elongation
The basics of elongation are the same in prokaryotes and eukaryotes. The intact ribosome has three compartments: the A site binds incoming aminoacyl tRNAs; the P site binds tRNAs carrying the growing polypeptide chain; the E site releases dissociated tRNAs so that they can be recharged with amino acids. The initiator tRNA, rMet-tRNA in E. coli and Met-tRNAi in eukaryotes and archaea, binds directly to the P site. This creates an initiation complex with a free A site ready to accept the aminoacyl-tRNA corresponding to the first codon after the AUG.
The aminoacyl-tRNA with an anticodon complementary to the A site codon lands in the A site. A peptide bond is formed between the amino group of the A site amino acid and the carboxyl group of the most-recently attached amino acid in the growing polypeptide chain attached to the P-site tRNA.The formation of the peptide bond is catalyzed by peptidyl transferase, an RNA-based enzyme that is integrated into the large ribosomal subunit. The energy for the peptide bond formation is derived from GTP hydrolysis, which is catalyzed by a separate elongation factor.
Catalyzing the formation of a peptide bond removes the bond holding the growing polypeptide chain to the P-site tRNA. The growing polypeptide chain is transferred to the amino end of the incoming amino acid, and the A-site tRNA temporarily holds the growing polypeptide chain, while the P-site tRNA is now empty or uncharged.
The ribosome moves three nucleotides down the mRNA. The tRNAs are basepaired to a codon on the mRNA, so as the ribosome moves over the mRNA, the tRNAs stay in place while the ribosome moves and each tRNA is moved into the next tRNA binding site. The E site moves over the former P-site tRNA, now empty or uncharged, the P site moves over the former A-site tRNA, now carrying the growing polypeptide chain, and the A site moves over a new codon. In the E site, the uncharged tRNA detaches from its anticodon and is expelled. A new aminoacyl-tRNA with an anticodon complementary to the new A-site codon enters the ribosome at the A site and the elongation process repeats itself. The energy for each step of the ribosome is donated by an elongation factor that hydrolyzes GTP.
Translation termination
Termination of translation occurs when the ribosome moves over a stop codon (UAA, UAG, or UGA). There are no tRNAs with anticodons complementary to stop codons, so no tRNAs enter the A site. Instead, in both prokaryotes and eukaryotes, a protein called a release factor enters the A site. The release factors cause the ribosome peptidyl transferase to add a water molecule to the carboxyl end of the most recently added amino acid in the growing polypeptide chain attached to the P-site tRNA. This causes the polypeptide chain to detach from its tRNA, and the newly-made polypeptide is released. The small and large ribosomal subunits dissociate from the mRNA and from each other; they are recruited almost immediately into another translation initiation complex. After many ribosomes have completed translation, the mRNA is degraded so the nucleotides can be reused in another transcription reaction.
Interactive Element
Modeling translation: This interactive models the process of translation in eukaryotes.
Key Points
• Protein synthesis, or translation, begins with a process known as pre-initiation, when the small ribosmal subunit, the mRNA template, initiator factors, and a special initiator tRNA, come together.
• During translocation and elongation, the ribosome moves one codon 3′ down the mRNA, brings in a charged tRNA to the A site, transfers the growing polypeptide chain from the P-site tRNA to the carboxyl group of the A-site amino acid, and ejects the uncharged tRNA at the E site.
• When a stop or nonsense codon (UAA, UAG, or UGA) is reached on the mRNA, the ribosome terminates translation.
Key Terms
• translation: a process occurring in the ribosome in which a strand of messenger RNA (mRNA) guides assembly of a sequence of amino acids to make a protein | textbooks/bio/Introductory_and_General_Biology/Book%3A_General_Biology_(Boundless)/15%3A_Genes_and_Proteins/15.11%3A_Ribosomes_and_Protein_Synthesis_-_The_Mechanism_of_Protein_Synthesis.txt |
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