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Cell_Biology_Alberts_410	Cell_Biology_Alberts	a crystal of salt, NaCl Charged groups are shielded by their interactions with water molecules. Electrostatic attractions are therefore quite weak in water. Similarly, ions in solution can cluster around charged groups and further weaken these attractions. Despite being weakened by water and salt, electrostatic attractions are very important in biological systems. For example, an enzyme that binds a positively charged substrate will often have a negatively charged amino acid side chain at the appropriate place. PaNel 2–4: an Outline of Some of the Types of Sugars Commonly Found in Cells Monosaccharides usually have the general formula (CH2O) n, where n can be 3, 4, 5, 6, 7, or 8, and have two or more hydroxyl groups. They either contain an aldehyde group ( ) and are called aldoses, or a ketone group ( ) and are called ketoses. MONOSACCHARIDESC O C O H	Cell_Biology_Alberts. a crystal of salt, NaCl Charged groups are shielded by their interactions with water molecules. Electrostatic attractions are therefore quite weak in water. Similarly, ions in solution can cluster around charged groups and further weaken these attractions. Despite being weakened by water and salt, electrostatic attractions are very important in biological systems. For example, an enzyme that binds a positively charged substrate will often have a negatively charged amino acid side chain at the appropriate place. PaNel 2–4: an Outline of Some of the Types of Sugars Commonly Found in Cells Monosaccharides usually have the general formula (CH2O) n, where n can be 3, 4, 5, 6, 7, or 8, and have two or more hydroxyl groups. They either contain an aldehyde group ( ) and are called aldoses, or a ketone group ( ) and are called ketoses. MONOSACCHARIDESC O C O H
Cell_Biology_Alberts_411	Cell_Biology_Alberts	In aqueous solution, the aldehyde or ketone group of a sugar Many monosaccharides differ only in the spatial arrangementmolecule tends to react with a hydroxyl group of the same of atoms—that is, they are isomers. For example, glucose,molecule, thereby closing the molecule into a ring. galactose, and mannose have the same formula (C6H12O6) but differ in the arrangement of groups around one or two carbon atoms. chemical properties of the sugars. But they are recognized by enzymes and other proteins and therefore can have major 5CH2OH has a number. biological effects.	Cell_Biology_Alberts. In aqueous solution, the aldehyde or ketone group of a sugar Many monosaccharides differ only in the spatial arrangementmolecule tends to react with a hydroxyl group of the same of atoms—that is, they are isomers. For example, glucose,molecule, thereby closing the molecule into a ring. galactose, and mannose have the same formula (C6H12O6) but differ in the arrangement of groups around one or two carbon atoms. chemical properties of the sugars. But they are recognized by enzymes and other proteins and therefore can have major 5CH2OH has a number. biological effects.
Cell_Biology_Alberts_412	Cell_Biology_Alberts	˜ AND ° LINKS The hydroxyl group on the carbon that carries the aldehyde or ketone can rapidly change from one position to the other. These two positions are called ˜ and °. As soon as one sugar is linked to another, the ˜ or ° form is frozen. OH O OH O ° hydroxyl ˜ hydroxyl CH2OH NH2 H O OH OH HO glucosamine CH2OH O OH OH HO CH3 O NH C H N-acetylglucosamine C O OH OH OH HO OH glucuronic acid O CH2OH HO O OH OH CH2OH OH HOCH2 HO CH2OH HO O OH OH OH CH2OH OH HOCH2 HO H O + sucrose ˜glucose °fructoseDISACCHARIDES The carbon that carries the aldehyde or the ketone can react with any hydroxyl group on a second sugar molecule to form a disaccharide. The linkage is called a glycosidic bond. Three common disaccharides are maltose (glucose + glucose) lactose (galactose + glucose) sucrose (glucose + fructose) The reaction forming sucrose is shown here. H2O O O O OLIGOSACCHARIDES AND POLYSACCHARIDES Large linear and branched molecules can be made from simple repeating sugar subunits. Short	Cell_Biology_Alberts. ˜ AND ° LINKS The hydroxyl group on the carbon that carries the aldehyde or ketone can rapidly change from one position to the other. These two positions are called ˜ and °. As soon as one sugar is linked to another, the ˜ or ° form is frozen. OH O OH O ° hydroxyl ˜ hydroxyl CH2OH NH2 H O OH OH HO glucosamine CH2OH O OH OH HO CH3 O NH C H N-acetylglucosamine C O OH OH OH HO OH glucuronic acid O CH2OH HO O OH OH CH2OH OH HOCH2 HO CH2OH HO O OH OH OH CH2OH OH HOCH2 HO H O + sucrose ˜glucose °fructoseDISACCHARIDES The carbon that carries the aldehyde or the ketone can react with any hydroxyl group on a second sugar molecule to form a disaccharide. The linkage is called a glycosidic bond. Three common disaccharides are maltose (glucose + glucose) lactose (galactose + glucose) sucrose (glucose + fructose) The reaction forming sucrose is shown here. H2O O O O OLIGOSACCHARIDES AND POLYSACCHARIDES Large linear and branched molecules can be made from simple repeating sugar subunits. Short
Cell_Biology_Alberts_413	Cell_Biology_Alberts	+ fructose) The reaction forming sucrose is shown here. H2O O O O OLIGOSACCHARIDES AND POLYSACCHARIDES Large linear and branched molecules can be made from simple repeating sugar subunits. Short chains are called oligosaccharides, while long chains are called polysaccharides. Glycogen, for example, is a polysaccharide made entirely of glucose units joined together. branch points glycogen CH2OH NH O CH2OH O CH2OH O OH O HO OH HO O OH NH O O HO CH3 O In many cases a sugar sequence is nonrepetitive. Many different molecules are possible. Such complex oligosaccharides are usually linked to proteins or to lipids, as is this oligosaccharide, which is part of a cell-surface molecule that defnes a particular blood group. COMPLEX OLIGOSACCHARIDES C O CH3 C O CH3 SUGAR DERIVATIVES The hydroxyl groups of a simple monosaccharide such as glucose can be replaced by other groups. For example, 97	Cell_Biology_Alberts. + fructose) The reaction forming sucrose is shown here. H2O O O O OLIGOSACCHARIDES AND POLYSACCHARIDES Large linear and branched molecules can be made from simple repeating sugar subunits. Short chains are called oligosaccharides, while long chains are called polysaccharides. Glycogen, for example, is a polysaccharide made entirely of glucose units joined together. branch points glycogen CH2OH NH O CH2OH O CH2OH O OH O HO OH HO O OH NH O O HO CH3 O In many cases a sugar sequence is nonrepetitive. Many different molecules are possible. Such complex oligosaccharides are usually linked to proteins or to lipids, as is this oligosaccharide, which is part of a cell-surface molecule that defnes a particular blood group. COMPLEX OLIGOSACCHARIDES C O CH3 C O CH3 SUGAR DERIVATIVES The hydroxyl groups of a simple monosaccharide such as glucose can be replaced by other groups. For example, 97
Cell_Biology_Alberts_414	Cell_Biology_Alberts	Fatty acids are stored as an energy reserve (fats and oils) through an ester linkage to glycerol to form triacylglycerols, also known as triglycerides. H2COCOHCOCOH2COCOH2COHHCOHH2COHglycerol TRIACYLGLYCEROLS These are carboxylic acids with long hydrocarbon tails. COOHCH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH3COOHCH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2COOHCH2CH2CH2CH2CH2CH2CH2CHCHCH2CH2CH2CH2CH2CH2CH2CH3CH3stearic acid (C18) palmitic acid (C16) oleic acid (C18) COMMON FATTY ACIDS OOCstearic acid This double bond is rigid and creates a kink in the chain. The rest of the chain is free to rotate about the other C–C bonds. –OCARBOXYL GROUP O_OCOOCNOCCHIf free, the carboxyl group of a fatty acid will be ionized. But more usually it is linked to other groups to form either esters or amides. PHOSPHOLIPIDS CH2CHCH2PO_OOOhydrophobic fatty acid tails general structure of a phospholipid –OOColeic acid space-flling model carbon skeleton hydrophilic head choline In phospholipids, two	Cell_Biology_Alberts. Fatty acids are stored as an energy reserve (fats and oils) through an ester linkage to glycerol to form triacylglycerols, also known as triglycerides. H2COCOHCOCOH2COCOH2COHHCOHH2COHglycerol TRIACYLGLYCEROLS These are carboxylic acids with long hydrocarbon tails. COOHCH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH3COOHCH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2COOHCH2CH2CH2CH2CH2CH2CH2CHCHCH2CH2CH2CH2CH2CH2CH2CH3CH3stearic acid (C18) palmitic acid (C16) oleic acid (C18) COMMON FATTY ACIDS OOCstearic acid This double bond is rigid and creates a kink in the chain. The rest of the chain is free to rotate about the other C–C bonds. –OCARBOXYL GROUP O_OCOOCNOCCHIf free, the carboxyl group of a fatty acid will be ionized. But more usually it is linked to other groups to form either esters or amides. PHOSPHOLIPIDS CH2CHCH2PO_OOOhydrophobic fatty acid tails general structure of a phospholipid –OOColeic acid space-flling model carbon skeleton hydrophilic head choline In phospholipids, two
Cell_Biology_Alberts_415	Cell_Biology_Alberts	amides. PHOSPHOLIPIDS CH2CHCH2PO_OOOhydrophobic fatty acid tails general structure of a phospholipid –OOColeic acid space-flling model carbon skeleton hydrophilic head choline In phospholipids, two of the –OH groups in glycerol are linked to fatty acids, while the third –OH group is linked to phosphoric acid. The phosphate is further linked to one of a variety of small polar groups, such as choline. space-flling model of the phospholipid phosphatidylcholine Hundreds of different kinds of fatty acids exist. Some have one or more double bonds in their hydrocarbon tail and are said to be unsaturated. Fatty acids with no double bonds are saturated. Phospholipids are the major constituents of cell membranes. UNSATURATED SATURATED 98 PaNel 2–5: Fatty acids and Other lipids	Cell_Biology_Alberts. amides. PHOSPHOLIPIDS CH2CHCH2PO_OOOhydrophobic fatty acid tails general structure of a phospholipid –OOColeic acid space-flling model carbon skeleton hydrophilic head choline In phospholipids, two of the –OH groups in glycerol are linked to fatty acids, while the third –OH group is linked to phosphoric acid. The phosphate is further linked to one of a variety of small polar groups, such as choline. space-flling model of the phospholipid phosphatidylcholine Hundreds of different kinds of fatty acids exist. Some have one or more double bonds in their hydrocarbon tail and are said to be unsaturated. Fatty acids with no double bonds are saturated. Phospholipids are the major constituents of cell membranes. UNSATURATED SATURATED 98 PaNel 2–5: Fatty acids and Other lipids
Cell_Biology_Alberts_416	Cell_Biology_Alberts	Fatty acids have a hydrophilic head and a hydrophobic tail. In water they can form a surface flm or form small micelles. Their derivatives can form larger aggregates held together by hydrophobic forces: Triacylglycerols (triglycerides) can form large spherical fat droplets in the cell cytoplasm. Phospholipids and glycolipids form self-sealing lipid bilayers that are the basis for all cell membranes. 200 nm or more micelle long-chain polymers of isoprene O OTHER LIPIDS Lipids are defned as the water-insoluble molecules in cells that are soluble in organic solvents. Two other common types of lipids are steroids and polyisoprenoids. Both are made from isoprene units. CH3CCHCH2CH2isoprene STEROIDS Steroids have a common multiple-ring structure.	Cell_Biology_Alberts. Fatty acids have a hydrophilic head and a hydrophobic tail. In water they can form a surface flm or form small micelles. Their derivatives can form larger aggregates held together by hydrophobic forces: Triacylglycerols (triglycerides) can form large spherical fat droplets in the cell cytoplasm. Phospholipids and glycolipids form self-sealing lipid bilayers that are the basis for all cell membranes. 200 nm or more micelle long-chain polymers of isoprene O OTHER LIPIDS Lipids are defned as the water-insoluble molecules in cells that are soluble in organic solvents. Two other common types of lipids are steroids and polyisoprenoids. Both are made from isoprene units. CH3CCHCH2CH2isoprene STEROIDS Steroids have a common multiple-ring structure.
Cell_Biology_Alberts_417	Cell_Biology_Alberts	STEROIDS Steroids have a common multiple-ring structure. GLYCOLIPIDS Like phospholipids, these compounds are composed of a hydrophobic region, containing two long hydrocarbon tails and a polar region, which contains one or more sugars and, unlike phospholipids, no phosphate. CCCH2HNHOHHOCOsugar a simple glycolipid Hdolichol phosphate—used to carry activated sugars in the membrane-associated synthesis of glycoproteins and some polysaccharides galactose BASES The bases are nitrogen-containing ring compounds, either pyrimidines or purines. CCCHCNHNHOOCCHCNHNONH2H3CCCHCNHNHOOHCHCUCTuracilcytosinethymineN N 1 2 3 4 5 6 N N 1 2 3 4 5 6N N 7 8 9 O N N H C C C C N NH NH2 HC N N H C C C CH N N HC NH2 adenine guanine A G PYRIMIDINE PURINE 100 PaNel 2–6: a Survey of the Nucleotides	Cell_Biology_Alberts. STEROIDS Steroids have a common multiple-ring structure. GLYCOLIPIDS Like phospholipids, these compounds are composed of a hydrophobic region, containing two long hydrocarbon tails and a polar region, which contains one or more sugars and, unlike phospholipids, no phosphate. CCCH2HNHOHHOCOsugar a simple glycolipid Hdolichol phosphate—used to carry activated sugars in the membrane-associated synthesis of glycoproteins and some polysaccharides galactose BASES The bases are nitrogen-containing ring compounds, either pyrimidines or purines. CCCHCNHNHOOCCHCNHNONH2H3CCCHCNHNHOOHCHCUCTuracilcytosinethymineN N 1 2 3 4 5 6 N N 1 2 3 4 5 6N N 7 8 9 O N N H C C C C N NH NH2 HC N N H C C C CH N N HC NH2 adenine guanine A G PYRIMIDINE PURINE 100 PaNel 2–6: a Survey of the Nucleotides
Cell_Biology_Alberts_418	Cell_Biology_Alberts	NUCLEOTIDESA nucleotide consists of a nitrogen-containing base, a fve-carbon sugar, and one or more phosphate groups. HHONH2OCH2OHOHBASE PHOSPHATE SUGAR Nucleotides are the subunits of the nucleic acids.The phosphate makes a nucleotide negatively charged. PHOSPHATES The phosphates are normally joined to the C5 hydroxyl of the ribose or deoxyribose sugar (designated 5'). Mono-, di-, and triphosphates are common. The base is linked to the same carbon (C1) used in sugar–sugar bonds. SUGARS Each numbered carbon on the sugar of a nucleotide is followed by a prime mark; therefore, one speaks of the “5-prime carbon,” etc. OH OH O H H HOCH2 OH H H OH H O H H HOCH2 OH H H PENTOSE a fve-carbon sugar O 4’ 3’ 2’ 1’ C 5’ two kinds are used ˜-D-ribose used in ribonucleic acid ˜-D-2-deoxyribose used in deoxyribonucleic acid	Cell_Biology_Alberts. NUCLEOTIDESA nucleotide consists of a nitrogen-containing base, a fve-carbon sugar, and one or more phosphate groups. HHONH2OCH2OHOHBASE PHOSPHATE SUGAR Nucleotides are the subunits of the nucleic acids.The phosphate makes a nucleotide negatively charged. PHOSPHATES The phosphates are normally joined to the C5 hydroxyl of the ribose or deoxyribose sugar (designated 5'). Mono-, di-, and triphosphates are common. The base is linked to the same carbon (C1) used in sugar–sugar bonds. SUGARS Each numbered carbon on the sugar of a nucleotide is followed by a prime mark; therefore, one speaks of the “5-prime carbon,” etc. OH OH O H H HOCH2 OH H H OH H O H H HOCH2 OH H H PENTOSE a fve-carbon sugar O 4’ 3’ 2’ 1’ C 5’ two kinds are used ˜-D-ribose used in ribonucleic acid ˜-D-2-deoxyribose used in deoxyribonucleic acid
Cell_Biology_Alberts_419	Cell_Biology_Alberts	NOMENCLATURE A nucleoside or nucleotide is named according to its nitrogenous base. BASE adenine guanine cytosine uracil thymine NUCLEOSIDE adenosine guanosine cytidine uridine thymidine ABBR. A G C U T Single-letter abbreviations are used variously as shorthand for (1) the base alone, (2) the nucleoside, or (3) the whole nucleotide— the context will usually make clear which of the three entities is meant. When the context is not suffcient, we will add the terms “base”, “nucleoside”, “nucleotide”, or—as in the examples below—use the full 3-letter nucleotide code. AMP dAMP UDP ATP = adenosine monophosphate = deoxyadenosine monophosphate = uridine diphosphate = adenosine triphosphate sugar base sugar base BASE + SUGAR = NUCLEOSIDE BASE + SUGAR + PHOSPHATE = NUCLEOTIDE NUCLEIC ACIDS Nucleotides are joined together by a phosphodiester linkage between 5’ and 3’ carbon atoms to form nucleic acids. The linear sequence of nucleotides in a nucleic acid chain is commonly abbreviated by a	Cell_Biology_Alberts. NOMENCLATURE A nucleoside or nucleotide is named according to its nitrogenous base. BASE adenine guanine cytosine uracil thymine NUCLEOSIDE adenosine guanosine cytidine uridine thymidine ABBR. A G C U T Single-letter abbreviations are used variously as shorthand for (1) the base alone, (2) the nucleoside, or (3) the whole nucleotide— the context will usually make clear which of the three entities is meant. When the context is not suffcient, we will add the terms “base”, “nucleoside”, “nucleotide”, or—as in the examples below—use the full 3-letter nucleotide code. AMP dAMP UDP ATP = adenosine monophosphate = deoxyadenosine monophosphate = uridine diphosphate = adenosine triphosphate sugar base sugar base BASE + SUGAR = NUCLEOSIDE BASE + SUGAR + PHOSPHATE = NUCLEOTIDE NUCLEIC ACIDS Nucleotides are joined together by a phosphodiester linkage between 5’ and 3’ carbon atoms to form nucleic acids. The linear sequence of nucleotides in a nucleic acid chain is commonly abbreviated by a
Cell_Biology_Alberts_420	Cell_Biology_Alberts	are joined together by a phosphodiester linkage between 5’ and 3’ carbon atoms to form nucleic acids. The linear sequence of nucleotides in a nucleic acid chain is commonly abbreviated by a one-letter code, such as A—G—C—T—T—A—C—A, with the 5’ end of the chain at the left. OOHsugar base CH2OO––OPO+OOHsugarbaseCH2H2OOO––OPOOsugarbaseCH2OO––OPOOsugarbase CH2PO–OOO5’OH3’3’ end of chain 3’5’phosphodiester linkage 5’ end of chain example: DNA OO––OPOO–POOOO–PONUCLEOTIDES HAVE MANY OTHER FUNCTIONS OCH2NNNNNH2OHOH1 They carry chemical energy in their easily hydrolyzed phosphoanhydride bonds. OOO–POCH2NNNNNH2OH2 They combine with other groups to form coenzymes. OO–POOCCCCNCCCNCCHSOOHHHHHHHHHHHHHHOCH3example: coenzyme A (CoA) CH33 They are used as specifc signaling molecules in the cell. OOO–POCH2NNNNNH2OOHexample: cyclic AMP (cAMP) phosphoanhydride bonds example: ATP (or ) OPO–O–OATPP proceed in cells only because they are coupled to very favorable reactions that drive them. The question of	Cell_Biology_Alberts. are joined together by a phosphodiester linkage between 5’ and 3’ carbon atoms to form nucleic acids. The linear sequence of nucleotides in a nucleic acid chain is commonly abbreviated by a one-letter code, such as A—G—C—T—T—A—C—A, with the 5’ end of the chain at the left. OOHsugar base CH2OO––OPO+OOHsugarbaseCH2H2OOO––OPOOsugarbaseCH2OO––OPOOsugarbase CH2PO–OOO5’OH3’3’ end of chain 3’5’phosphodiester linkage 5’ end of chain example: DNA OO––OPOO–POOOO–PONUCLEOTIDES HAVE MANY OTHER FUNCTIONS OCH2NNNNNH2OHOH1 They carry chemical energy in their easily hydrolyzed phosphoanhydride bonds. OOO–POCH2NNNNNH2OH2 They combine with other groups to form coenzymes. OO–POOCCCCNCCCNCCHSOOHHHHHHHHHHHHHHOCH3example: coenzyme A (CoA) CH33 They are used as specifc signaling molecules in the cell. OOO–POCH2NNNNNH2OOHexample: cyclic AMP (cAMP) phosphoanhydride bonds example: ATP (or ) OPO–O–OATPP proceed in cells only because they are coupled to very favorable reactions that drive them. The question of
Cell_Biology_Alberts_421	Cell_Biology_Alberts	cyclic AMP (cAMP) phosphoanhydride bonds example: ATP (or ) OPO–O–OATPP proceed in cells only because they are coupled to very favorable reactions that drive them. The question of whether a reaction dynamics—that are required for understanding what free energy is and why it is so important to cells.	Cell_Biology_Alberts. cyclic AMP (cAMP) phosphoanhydride bonds example: ATP (or ) OPO–O–OATPP proceed in cells only because they are coupled to very favorable reactions that drive them. The question of whether a reaction dynamics—that are required for understanding what free energy is and why it is so important to cells.
Cell_Biology_Alberts_422	Cell_Biology_Alberts	ENERGY RELEASED BY CHANGES IN CHEMICAL BONDING IS CONVERTED INTO HEAT of molecular collisions that heat up frst the walls of the box and then the outside world (represented by the sea in our example). In the end, the system returns to its initial temperature, by which time all the chemical-bond energy released in the box has been converted into heat energy and transferred out of the box to the surroundings. According to the frst law, the change in the energy in the box (˜Ebox, which we shall denote as ˜E) must be equal and opposite to the amount of heat energy transferred, which we shall designate as h: that is, ˜E = _h. Thus, the energy in the box (E) decreases when heat leaves the system. E also can change during a reaction as a result of work being done on the outside world. For example, suppose that there is a small increase in the volume (˜V) of the box during a reaction. Since the walls of the box must push against the constant pressure (P) in the surroundings in order to	Cell_Biology_Alberts. ENERGY RELEASED BY CHANGES IN CHEMICAL BONDING IS CONVERTED INTO HEAT of molecular collisions that heat up frst the walls of the box and then the outside world (represented by the sea in our example). In the end, the system returns to its initial temperature, by which time all the chemical-bond energy released in the box has been converted into heat energy and transferred out of the box to the surroundings. According to the frst law, the change in the energy in the box (˜Ebox, which we shall denote as ˜E) must be equal and opposite to the amount of heat energy transferred, which we shall designate as h: that is, ˜E = _h. Thus, the energy in the box (E) decreases when heat leaves the system. E also can change during a reaction as a result of work being done on the outside world. For example, suppose that there is a small increase in the volume (˜V) of the box during a reaction. Since the walls of the box must push against the constant pressure (P) in the surroundings in order to
Cell_Biology_Alberts_423	Cell_Biology_Alberts	example, suppose that there is a small increase in the volume (˜V) of the box during a reaction. Since the walls of the box must push against the constant pressure (P) in the surroundings in order to expand, this does work on the outside world and requires energy. The energy used is P(˜V), which according to the frst law must decrease the energy in the box (E) by the same amount. In most reactions, chemical-bond energy is converted into both work and heat. Enthalpy (H) is a composite function that includes both of these (H = E + PV). To be rigorous, it is the change in enthalpy (˜H) in an enclosed system, and not the change in energy, that is equal to the heat transferred to the outside world during a reaction. Reactions in which H decreases release heat to the surroundings and are said to be “exothermic,” while reactions in which H increases absorb heat from the surroundings and are said to be “endothermic.” Thus, _h = ˜H. However, the volume change is negligible in most biological	Cell_Biology_Alberts. example, suppose that there is a small increase in the volume (˜V) of the box during a reaction. Since the walls of the box must push against the constant pressure (P) in the surroundings in order to expand, this does work on the outside world and requires energy. The energy used is P(˜V), which according to the frst law must decrease the energy in the box (E) by the same amount. In most reactions, chemical-bond energy is converted into both work and heat. Enthalpy (H) is a composite function that includes both of these (H = E + PV). To be rigorous, it is the change in enthalpy (˜H) in an enclosed system, and not the change in energy, that is equal to the heat transferred to the outside world during a reaction. Reactions in which H decreases release heat to the surroundings and are said to be “exothermic,” while reactions in which H increases absorb heat from the surroundings and are said to be “endothermic.” Thus, _h = ˜H. However, the volume change is negligible in most biological
Cell_Biology_Alberts_424	Cell_Biology_Alberts	to be “exothermic,” while reactions in which H increases absorb heat from the surroundings and are said to be “endothermic.” Thus, _h = ˜H. However, the volume change is negligible in most biological reactions, so to a good approximation An enclosed system is defned as a collection of molecules that does not exchange matter with the rest of the universe (for example, the “cell in a box” shown above). Any such system will contain molecules with a total energy E. This energy will be distributed in a variety of ways: some as the translational energy of the molecules, some as their vibrational and rotational energies, but most as the bonding energies between the individual atoms that make up the molecules. Suppose that a reaction occurs in the system. The frst law of thermodynamics places a constraint on what types of reactions are possible: it states that “in any process, the total energy of the universe remains constant.” For example, suppose that reaction A B occurs somewhere in the	Cell_Biology_Alberts. to be “exothermic,” while reactions in which H increases absorb heat from the surroundings and are said to be “endothermic.” Thus, _h = ˜H. However, the volume change is negligible in most biological reactions, so to a good approximation An enclosed system is defned as a collection of molecules that does not exchange matter with the rest of the universe (for example, the “cell in a box” shown above). Any such system will contain molecules with a total energy E. This energy will be distributed in a variety of ways: some as the translational energy of the molecules, some as their vibrational and rotational energies, but most as the bonding energies between the individual atoms that make up the molecules. Suppose that a reaction occurs in the system. The frst law of thermodynamics places a constraint on what types of reactions are possible: it states that “in any process, the total energy of the universe remains constant.” For example, suppose that reaction A B occurs somewhere in the
Cell_Biology_Alberts_425	Cell_Biology_Alberts	constraint on what types of reactions are possible: it states that “in any process, the total energy of the universe remains constant.” For example, suppose that reaction A B occurs somewhere in the box and releases a great deal of chemical-bond energy. This energy will initially increase the intensity of molecular motions (translational, vibrational, and rotational) in the system, which is equivalent to raising its temperature. However, these increased motions will soon be transferred out of the system by a series _h = ˜H = ˜E BOX CELL SEA UNIVERSE ~ THE SECOND LAW OF THERMODYNAMICS Consider a container in which 1000 coins are all lying heads up. If the container is shaken vigorously, subjecting the coins to the types of random motions that all molecules experience due to their frequent collisions with other molecules, one will end up with about half the coins oriented heads down. The reason for this reorientation is that there is only a single way in which the original orderly state	Cell_Biology_Alberts. constraint on what types of reactions are possible: it states that “in any process, the total energy of the universe remains constant.” For example, suppose that reaction A B occurs somewhere in the box and releases a great deal of chemical-bond energy. This energy will initially increase the intensity of molecular motions (translational, vibrational, and rotational) in the system, which is equivalent to raising its temperature. However, these increased motions will soon be transferred out of the system by a series _h = ˜H = ˜E BOX CELL SEA UNIVERSE ~ THE SECOND LAW OF THERMODYNAMICS Consider a container in which 1000 coins are all lying heads up. If the container is shaken vigorously, subjecting the coins to the types of random motions that all molecules experience due to their frequent collisions with other molecules, one will end up with about half the coins oriented heads down. The reason for this reorientation is that there is only a single way in which the original orderly state
Cell_Biology_Alberts_426	Cell_Biology_Alberts	with other molecules, one will end up with about half the coins oriented heads down. The reason for this reorientation is that there is only a single way in which the original orderly state of the coins can be reinstated (every coin must lie heads up), whereas there are many different ways (about 10298) to achieve a disorderly state in which there is an equal mixture of heads and tails; in fact, there are more ways to achieve a 50-50 state than to achieve any other state. Each state has a probability of occurrence that is proportional to the number of ways it can be realized. The second law of thermo-dynamics states that “systems will change spontaneously from states of lower probability to states of higher probability.” Since states of lower probability are more “ordered” than states of high probability, the second law can be restated: “the universe constantly changes so as to become more disordered.”	Cell_Biology_Alberts. with other molecules, one will end up with about half the coins oriented heads down. The reason for this reorientation is that there is only a single way in which the original orderly state of the coins can be reinstated (every coin must lie heads up), whereas there are many different ways (about 10298) to achieve a disorderly state in which there is an equal mixture of heads and tails; in fact, there are more ways to achieve a 50-50 state than to achieve any other state. Each state has a probability of occurrence that is proportional to the number of ways it can be realized. The second law of thermo-dynamics states that “systems will change spontaneously from states of lower probability to states of higher probability.” Since states of lower probability are more “ordered” than states of high probability, the second law can be restated: “the universe constantly changes so as to become more disordered.”
Cell_Biology_Alberts_427	Cell_Biology_Alberts	THE ENTROPY, S The second law (but not the frst law) allows one to predict the direction of a particular reaction. But to make it useful for this purpose, one needs a convenient measure of the probability or, equivalently, the degree of disorder of a state. The entropy (S) is such a measure. It is a logarithmic function of the probability such that the change in entropy (˜S) that occurs when the reaction A	Cell_Biology_Alberts. THE ENTROPY, S The second law (but not the frst law) allows one to predict the direction of a particular reaction. But to make it useful for this purpose, one needs a convenient measure of the probability or, equivalently, the degree of disorder of a state. The entropy (S) is such a measure. It is a logarithmic function of the probability such that the change in entropy (˜S) that occurs when the reaction A
Cell_Biology_Alberts_428	Cell_Biology_Alberts	B converts one mole of A into one mole of B is where pA and pB are the probabilities of the two states A and B, R is the gas constant (8.31 J K–1 mole_1), and ˜S is measured in entropy units (eu). In our initial example of 1000 coins, the relative probability of all heads (state A) versus half heads and half tails (state B) is equal to the ratio of the number of different ways that the two results can be obtained. One can calculate that pA = 1 and pB = 1000!(500! x 500!) = 10299. Therefore, the entropy change for the reorientation of the coins when their container is vigorously shaken and an equal mixture of heads and tails is obtained is R In (10298), or about 1370 eu per mole of such containers (6 x 1023 containers). We see that, because ˜S defned above is positive for the transition from state A to state B (pB /pA > 1), reactions with a large increase in S (that is, for which ˜S > 0) are favored and will occur spontaneously.	Cell_Biology_Alberts. B converts one mole of A into one mole of B is where pA and pB are the probabilities of the two states A and B, R is the gas constant (8.31 J K–1 mole_1), and ˜S is measured in entropy units (eu). In our initial example of 1000 coins, the relative probability of all heads (state A) versus half heads and half tails (state B) is equal to the ratio of the number of different ways that the two results can be obtained. One can calculate that pA = 1 and pB = 1000!(500! x 500!) = 10299. Therefore, the entropy change for the reorientation of the coins when their container is vigorously shaken and an equal mixture of heads and tails is obtained is R In (10298), or about 1370 eu per mole of such containers (6 x 1023 containers). We see that, because ˜S defned above is positive for the transition from state A to state B (pB /pA > 1), reactions with a large increase in S (that is, for which ˜S > 0) are favored and will occur spontaneously.
Cell_Biology_Alberts_429	Cell_Biology_Alberts	As discussed in Chapter 2, heat energy causes the random commotion of molecules. Because the transfer of heat from an enclosed system to its surroundings increases the number of different arrangements that the molecules in the outside world can have, it increases their entropy. It can be shown that the release of a fxed quantity of heat energy has a greater disordering effect at low temperature than at high temperature, and that the value of ˜S for the surroundings, as defned above (˜Ssea), is precisely equal to h, the amount of heat transferred to the surroundings from the system, divided by the absolute temperature (T ):	Cell_Biology_Alberts. As discussed in Chapter 2, heat energy causes the random commotion of molecules. Because the transfer of heat from an enclosed system to its surroundings increases the number of different arrangements that the molecules in the outside world can have, it increases their entropy. It can be shown that the release of a fxed quantity of heat energy has a greater disordering effect at low temperature than at high temperature, and that the value of ˜S for the surroundings, as defned above (˜Ssea), is precisely equal to h, the amount of heat transferred to the surroundings from the system, divided by the absolute temperature (T ):
Cell_Biology_Alberts_430	Cell_Biology_Alberts	THE GIBBS FREE ENERGY, G When dealing with an enclosed biological system, one would like to have a simple way of predicting whether a given reaction will or will not occur spontaneously in the system. We have seen that the crucial question is whether the entropy change for the universe is positive or negative when that reaction occurs. In our idealized system, the cell in a box, there are two separate components to the entropy change of the universe—the entropy change for the system enclosed in the box and the entropy change for the surrounding “sea”—and both must be added together before any prediction can be made. For example, it is possible for a reaction to absorb heat and thereby decrease the entropy of the sea (˜Ssea < 0) and at the same time to cause such a large degree of disordering inside the box (˜Sbox > 0) that the total ˜Suniverse = ˜Ssea + ˜Sbox is greater than 0. In this case, the reaction will occur spontaneously, even though the sea gives up heat to the box during the	Cell_Biology_Alberts. THE GIBBS FREE ENERGY, G When dealing with an enclosed biological system, one would like to have a simple way of predicting whether a given reaction will or will not occur spontaneously in the system. We have seen that the crucial question is whether the entropy change for the universe is positive or negative when that reaction occurs. In our idealized system, the cell in a box, there are two separate components to the entropy change of the universe—the entropy change for the system enclosed in the box and the entropy change for the surrounding “sea”—and both must be added together before any prediction can be made. For example, it is possible for a reaction to absorb heat and thereby decrease the entropy of the sea (˜Ssea < 0) and at the same time to cause such a large degree of disordering inside the box (˜Sbox > 0) that the total ˜Suniverse = ˜Ssea + ˜Sbox is greater than 0. In this case, the reaction will occur spontaneously, even though the sea gives up heat to the box during the
Cell_Biology_Alberts_431	Cell_Biology_Alberts	inside the box (˜Sbox > 0) that the total ˜Suniverse = ˜Ssea + ˜Sbox is greater than 0. In this case, the reaction will occur spontaneously, even though the sea gives up heat to the box during the reaction. An example of such a reaction is the dissolving of sodium chloride in a beaker containing water (the “box”), which is a spontaneous process even though the temperature of the water drops as the salt goes into solution. Chemists have found it useful to defne a number of new “composite functions” that describe combinations of physical properties of a system. The properties that can be combined include the temperature (T), pressure (P), volume (V), energy (E), and entropy (S). The enthalpy (H) is one such composite function. But by far the most useful composite function for biologists is the Gibbs free energy, G. It serves as an accounting device that allows one to deduce the entropy change of the universe resulting from a chemical reaction in the box, while avoiding any separate	Cell_Biology_Alberts. inside the box (˜Sbox > 0) that the total ˜Suniverse = ˜Ssea + ˜Sbox is greater than 0. In this case, the reaction will occur spontaneously, even though the sea gives up heat to the box during the reaction. An example of such a reaction is the dissolving of sodium chloride in a beaker containing water (the “box”), which is a spontaneous process even though the temperature of the water drops as the salt goes into solution. Chemists have found it useful to defne a number of new “composite functions” that describe combinations of physical properties of a system. The properties that can be combined include the temperature (T), pressure (P), volume (V), energy (E), and entropy (S). The enthalpy (H) is one such composite function. But by far the most useful composite function for biologists is the Gibbs free energy, G. It serves as an accounting device that allows one to deduce the entropy change of the universe resulting from a chemical reaction in the box, while avoiding any separate
Cell_Biology_Alberts_432	Cell_Biology_Alberts	is the Gibbs free energy, G. It serves as an accounting device that allows one to deduce the entropy change of the universe resulting from a chemical reaction in the box, while avoiding any separate consideration of the entropy change in the sea. The defnition of G is where, for a box of volume V, H is the enthalpy described above (E + PV), T is the absolute temperature, and S is the entropy. Each of these quantities applies to the inside of the box only. The change in free energy during a reaction in the box (the G of the products minus the G of the starting materials) is denoted as ˜G and, as we shall now demonstrate, it is a direct measure of the amount of disorder that is created in the universe when the reaction occurs. G = H _ TS At constant temperature the change in free energy (˜G) during a reaction equals ˜H _ T˜S. Remembering that ˜H = _h, the heat absorbed from the sea, we have _˜G = _˜H + T˜S _˜G = h + T˜S, so _˜G/T = h/T + ˜S But h/T is equal to the entropy change of the	Cell_Biology_Alberts. is the Gibbs free energy, G. It serves as an accounting device that allows one to deduce the entropy change of the universe resulting from a chemical reaction in the box, while avoiding any separate consideration of the entropy change in the sea. The defnition of G is where, for a box of volume V, H is the enthalpy described above (E + PV), T is the absolute temperature, and S is the entropy. Each of these quantities applies to the inside of the box only. The change in free energy during a reaction in the box (the G of the products minus the G of the starting materials) is denoted as ˜G and, as we shall now demonstrate, it is a direct measure of the amount of disorder that is created in the universe when the reaction occurs. G = H _ TS At constant temperature the change in free energy (˜G) during a reaction equals ˜H _ T˜S. Remembering that ˜H = _h, the heat absorbed from the sea, we have _˜G = _˜H + T˜S _˜G = h + T˜S, so _˜G/T = h/T + ˜S But h/T is equal to the entropy change of the
Cell_Biology_Alberts_433	Cell_Biology_Alberts	during a reaction equals ˜H _ T˜S. Remembering that ˜H = _h, the heat absorbed from the sea, we have _˜G = _˜H + T˜S _˜G = h + T˜S, so _˜G/T = h/T + ˜S But h/T is equal to the entropy change of the sea (˜Ssea), and the ˜S in the above equation is ˜Sbox. Therefore _˜G/T = ˜Ssea + ˜Sbox = ˜Suniverse We conclude that the free-energy change is a direct measure of the entropy change of the universe. A reaction will proceed in the direction that causes the change in the free energy (˜G) to be less than zero, because in this case there will be a positive entropy change in the universe when the reaction occurs. For a complex set of coupled reactions involving many different molecules, the total free-energy change can be com-puted simply by adding up the free energies of all the different molecular species after the reaction and comparing this value with the sum of free energies before the reaction; for common substances the required free-energy values can be found from published tables. In	Cell_Biology_Alberts. during a reaction equals ˜H _ T˜S. Remembering that ˜H = _h, the heat absorbed from the sea, we have _˜G = _˜H + T˜S _˜G = h + T˜S, so _˜G/T = h/T + ˜S But h/T is equal to the entropy change of the sea (˜Ssea), and the ˜S in the above equation is ˜Sbox. Therefore _˜G/T = ˜Ssea + ˜Sbox = ˜Suniverse We conclude that the free-energy change is a direct measure of the entropy change of the universe. A reaction will proceed in the direction that causes the change in the free energy (˜G) to be less than zero, because in this case there will be a positive entropy change in the universe when the reaction occurs. For a complex set of coupled reactions involving many different molecules, the total free-energy change can be com-puted simply by adding up the free energies of all the different molecular species after the reaction and comparing this value with the sum of free energies before the reaction; for common substances the required free-energy values can be found from published tables. In
Cell_Biology_Alberts_434	Cell_Biology_Alberts	species after the reaction and comparing this value with the sum of free energies before the reaction; for common substances the required free-energy values can be found from published tables. In this way, one can predict the direction of a reaction and thereby readily check the feasibility of any proposed mechanism. Thus, for example, from the observed values for the magnitude of the electrochemical proton gradient across the inner mitochondrial membrane and the ˜G for ATP hydrolysis inside the mitochondrion, one can be certain that ATP synthase requires the passage of more than one proton for each molecule of ATP that it synthesizes. The value of ˜G for a reaction is a direct measure of how far the reaction is from equilibrium. The large negative value for ATP hydrolysis in a cell merely refects the fact that cells keep the ATP hydrolysis reaction as much as 10 orders of magnitude away from equilibrium. If a reaction reaches equilibrium, ˜G = 0, the reaction then proceeds at	Cell_Biology_Alberts. species after the reaction and comparing this value with the sum of free energies before the reaction; for common substances the required free-energy values can be found from published tables. In this way, one can predict the direction of a reaction and thereby readily check the feasibility of any proposed mechanism. Thus, for example, from the observed values for the magnitude of the electrochemical proton gradient across the inner mitochondrial membrane and the ˜G for ATP hydrolysis inside the mitochondrion, one can be certain that ATP synthase requires the passage of more than one proton for each molecule of ATP that it synthesizes. The value of ˜G for a reaction is a direct measure of how far the reaction is from equilibrium. The large negative value for ATP hydrolysis in a cell merely refects the fact that cells keep the ATP hydrolysis reaction as much as 10 orders of magnitude away from equilibrium. If a reaction reaches equilibrium, ˜G = 0, the reaction then proceeds at
Cell_Biology_Alberts_435	Cell_Biology_Alberts	merely refects the fact that cells keep the ATP hydrolysis reaction as much as 10 orders of magnitude away from equilibrium. If a reaction reaches equilibrium, ˜G = 0, the reaction then proceeds at precisely equal rates in the forward and backward direction. For ATP hydrolysis, equilibrium is reached when the vast majority of the ATP has been hydrolyzed, as occurs in a dead cell.	Cell_Biology_Alberts. merely refects the fact that cells keep the ATP hydrolysis reaction as much as 10 orders of magnitude away from equilibrium. If a reaction reaches equilibrium, ˜G = 0, the reaction then proceeds at precisely equal rates in the forward and backward direction. For ATP hydrolysis, equilibrium is reached when the vast majority of the ATP has been hydrolyzed, as occurs in a dead cell.
Cell_Biology_Alberts_436	Cell_Biology_Alberts	CH2OHOOHOHOHHOglucoseCH2OH+OOHOHOHHOglucose 6-phosphate + + + hexokinase CH2OOOHOHOHHOglucose 6-phosphate fructose 6-phosphate (ring form) (ring form) (open-chain form) 1 1 2 2 3 4 5 6 6 OHCCHOHCHOHCHOHCHOHCH2O3 4 5 (open-chain form) 1 1 2 2 6 CCHOHCHOHCHOHCH2OCH2OH334455phosphoglucoseisomeraseOH2CCH2OHOHOOHOH6+H+++phosphofructokinaseOH2CCH2OHOHOOHOHOH2COHOOHOHGlucose is phosphorylated by ATP to form a sugar phosphate. The negative charge of the phosphate prevents passage of the sugar phosphate through the plasma membrane, trapping glucose inside the cell. The six-carbon sugar is cleaved to produce two three-carbon molecules. Only the glyceraldehyde 3-phosphate can proceed immediately through glycolysis. A readily reversible rearrangement of the chemical structure (isomerization) moves the carbonyl oxygen from carbon 1 to carbon 2, forming a ketose from an aldose sugar. (See Panel 2–3, pp. 70–71.) The new hydroxyl group on carbon 1 is phosphorylated by ATP, in preparation for the	Cell_Biology_Alberts. CH2OHOOHOHOHHOglucoseCH2OH+OOHOHOHHOglucose 6-phosphate + + + hexokinase CH2OOOHOHOHHOglucose 6-phosphate fructose 6-phosphate (ring form) (ring form) (open-chain form) 1 1 2 2 3 4 5 6 6 OHCCHOHCHOHCHOHCHOHCH2O3 4 5 (open-chain form) 1 1 2 2 6 CCHOHCHOHCHOHCH2OCH2OH334455phosphoglucoseisomeraseOH2CCH2OHOHOOHOH6+H+++phosphofructokinaseOH2CCH2OHOHOOHOHOH2COHOOHOHGlucose is phosphorylated by ATP to form a sugar phosphate. The negative charge of the phosphate prevents passage of the sugar phosphate through the plasma membrane, trapping glucose inside the cell. The six-carbon sugar is cleaved to produce two three-carbon molecules. Only the glyceraldehyde 3-phosphate can proceed immediately through glycolysis. A readily reversible rearrangement of the chemical structure (isomerization) moves the carbonyl oxygen from carbon 1 to carbon 2, forming a ketose from an aldose sugar. (See Panel 2–3, pp. 70–71.) The new hydroxyl group on carbon 1 is phosphorylated by ATP, in preparation for the
Cell_Biology_Alberts_437	Cell_Biology_Alberts	the carbonyl oxygen from carbon 1 to carbon 2, forming a ketose from an aldose sugar. (See Panel 2–3, pp. 70–71.) The new hydroxyl group on carbon 1 is phosphorylated by ATP, in preparation for the formation of two three-carbon sugar phosphates. The entry of sugars into glycolysis is controlled at this step, through regulation of the enzyme phosphofructokinase. fructose 6-phosphate fructose 1,6-bisphosphate + (ring form) OHCCHOHaldolase (open-chain form) CCHOHCHOHCHOHCH2OCH2OOCCHOHHCH2OCH2OOOH2CCH2OOHOOHOHfructose 1,6-bisphosphate dihydroxyacetone phosphate glyceraldehyde 3-phosphate OFor each step, the part of the molecule that undergoes a change is shadowed in blue, and the name of the enzyme that catalyzes the reaction is in a yellow box. ATPATPADPADPP P P P P PP P P P P P P P CH2OStep 1 Step 2 Step 3 Step 4 104 PaNel 2–8: Details of the 10 Steps of Glycolysis + + enolase phosphoglycerate mutase + OO–CCHOHCH2O3-phosphoglycerate OO–CCHOCH2OH2-phosphoglycerate	Cell_Biology_Alberts. the carbonyl oxygen from carbon 1 to carbon 2, forming a ketose from an aldose sugar. (See Panel 2–3, pp. 70–71.) The new hydroxyl group on carbon 1 is phosphorylated by ATP, in preparation for the formation of two three-carbon sugar phosphates. The entry of sugars into glycolysis is controlled at this step, through regulation of the enzyme phosphofructokinase. fructose 6-phosphate fructose 1,6-bisphosphate + (ring form) OHCCHOHaldolase (open-chain form) CCHOHCHOHCHOHCH2OCH2OOCCHOHHCH2OCH2OOOH2CCH2OOHOOHOHfructose 1,6-bisphosphate dihydroxyacetone phosphate glyceraldehyde 3-phosphate OFor each step, the part of the molecule that undergoes a change is shadowed in blue, and the name of the enzyme that catalyzes the reaction is in a yellow box. ATPATPADPADPP P P P P PP P P P P P P P CH2OStep 1 Step 2 Step 3 Step 4 104 PaNel 2–8: Details of the 10 Steps of Glycolysis + + enolase phosphoglycerate mutase + OO–CCHOHCH2O3-phosphoglycerate OO–CCHOCH2OH2-phosphoglycerate
Cell_Biology_Alberts_438	Cell_Biology_Alberts	P P P P P P P CH2OStep 1 Step 2 Step 3 Step 4 104 PaNel 2–8: Details of the 10 Steps of Glycolysis + + enolase phosphoglycerate mutase + OO–CCHOHCH2O3-phosphoglycerate OO–CCHOCH2OH2-phosphoglycerate OO–CCHOCH2OH2-phosphoglycerate OO–CCOCH2H2Ophosphoenolpyruvate OO–CCOCH2phosphoenolpyruvate OO–CCOCH3pyruvate + phosphoglycerate kinaseOCCHOHCH2O1,3-bisphosphoglycerate + OO–CCHOHCH2O3-phosphoglycerate The two molecules of glyceraldehyde 3-phosphate are oxidized. The energy-generation phase of glycolysis begins, as NADH and a new high-energy anhydride linkage to phosphate are formed (see Figure 13–5). H++ ++ glyceraldehyde 3-phosphate dehydrogenaseOHCCHOHCH2Oglyceraldehyde 3-phosphate OOCCHOHCH2O1,3-bisphosphoglycerate H++ The transfer to ADP of the high-energy phosphate group that was generated in step 6 forms ATP. The remaining phosphate ester linkage in 3-phosphoglycerate, which has a relatively low free energy of hydrolysis, is moved from carbon 3 to carbon 2 to form	Cell_Biology_Alberts. P P P P P P P CH2OStep 1 Step 2 Step 3 Step 4 104 PaNel 2–8: Details of the 10 Steps of Glycolysis + + enolase phosphoglycerate mutase + OO–CCHOHCH2O3-phosphoglycerate OO–CCHOCH2OH2-phosphoglycerate OO–CCHOCH2OH2-phosphoglycerate OO–CCOCH2H2Ophosphoenolpyruvate OO–CCOCH2phosphoenolpyruvate OO–CCOCH3pyruvate + phosphoglycerate kinaseOCCHOHCH2O1,3-bisphosphoglycerate + OO–CCHOHCH2O3-phosphoglycerate The two molecules of glyceraldehyde 3-phosphate are oxidized. The energy-generation phase of glycolysis begins, as NADH and a new high-energy anhydride linkage to phosphate are formed (see Figure 13–5). H++ ++ glyceraldehyde 3-phosphate dehydrogenaseOHCCHOHCH2Oglyceraldehyde 3-phosphate OOCCHOHCH2O1,3-bisphosphoglycerate H++ The transfer to ADP of the high-energy phosphate group that was generated in step 6 forms ATP. The remaining phosphate ester linkage in 3-phosphoglycerate, which has a relatively low free energy of hydrolysis, is moved from carbon 3 to carbon 2 to form
Cell_Biology_Alberts_439	Cell_Biology_Alberts	that was generated in step 6 forms ATP. The remaining phosphate ester linkage in 3-phosphoglycerate, which has a relatively low free energy of hydrolysis, is moved from carbon 3 to carbon 2 to form 2-phosphoglycerate. The removal of water from 2-phosphoglycerate creates a high-energy enol phosphate linkage. The transfer to ADP of the high-energy phosphate group that was generated in step 9 forms ATP, completing glycolysis. + pyruvate kinase 1 2 3 ATPADPATPADPNADHNAD+Pi P P P P P P P P P P P OStep 6 Step 7 Step 8 Step 9 Step 10 105	Cell_Biology_Alberts. that was generated in step 6 forms ATP. The remaining phosphate ester linkage in 3-phosphoglycerate, which has a relatively low free energy of hydrolysis, is moved from carbon 3 to carbon 2 to form 2-phosphoglycerate. The removal of water from 2-phosphoglycerate creates a high-energy enol phosphate linkage. The transfer to ADP of the high-energy phosphate group that was generated in step 9 forms ATP, completing glycolysis. + pyruvate kinase 1 2 3 ATPADPATPADPNADHNAD+Pi P P P P P P P P P P P OStep 6 Step 7 Step 8 Step 9 Step 10 105
Cell_Biology_Alberts_440	Cell_Biology_Alberts	In addition to the pyruvate, the net products are two molecules glucose two molecules of ATP and two molecules of NADH. of pyruvate Step 2 An isomerization COO–	Cell_Biology_Alberts. In addition to the pyruvate, the net products are two molecules glucose two molecules of ATP and two molecules of NADH. of pyruvate Step 2 An isomerization COO–
Cell_Biology_Alberts_441	Cell_Biology_Alberts	After the enzyme removes a proton from the CH3 group on acetyl CoA, the negatively charged CH2 – forms a bond to a carbonyl carbon of oxaloacetate. The subsequent loss by hydrolysis of the coenzyme A (HS–CoA) drives the reaction strongly forward. acetyl CoA S-citryl-CoA intermediate citrateoxaloacetate COO–COO–OOCCSCoAcitrate synthase CH3CH2H2OOCSCoACH2COO–COO–CHOCH2CH2COO–COO–COO–CCH2CoAHSH+CoAHO+++Details of these eight steps are shown below. In this part of the panel, for each step, the part of the molecule that undergoes a change is shadowed in blue, and the name of the enzyme that catalyzes the reaction is in a yellow box. CH2COO–COO–COO–CHOCH2H2OH2OH2OCH2CO2CO2CO2COO–COO–COO–HCCHHOCH2COO–COO–COCH2CH2COO–COO–CH2CHCOO–COO–CHHOHCCOO–COO–CH2COO–COCH2SCoAOCH3SCoAacetyl CoA coenzyme A HSCoAHSHSCoAHSCoACH2OCCOO–COO–CH2OOCCOO–COO–COO–CH2CH3Cnext cycle + Step 1 Step 2 Step 3 Step 4 Step 6 Step 7 Step 8 Step 5 citrate (6C) isocitrate (6C) succinyl CoA (4C)succinate (4C) fumarate (4C)	Cell_Biology_Alberts. After the enzyme removes a proton from the CH3 group on acetyl CoA, the negatively charged CH2 – forms a bond to a carbonyl carbon of oxaloacetate. The subsequent loss by hydrolysis of the coenzyme A (HS–CoA) drives the reaction strongly forward. acetyl CoA S-citryl-CoA intermediate citrateoxaloacetate COO–COO–OOCCSCoAcitrate synthase CH3CH2H2OOCSCoACH2COO–COO–CHOCH2CH2COO–COO–COO–CCH2CoAHSH+CoAHO+++Details of these eight steps are shown below. In this part of the panel, for each step, the part of the molecule that undergoes a change is shadowed in blue, and the name of the enzyme that catalyzes the reaction is in a yellow box. CH2COO–COO–COO–CHOCH2H2OH2OH2OCH2CO2CO2CO2COO–COO–COO–HCCHHOCH2COO–COO–COCH2CH2COO–COO–CH2CHCOO–COO–CHHOHCCOO–COO–CH2COO–COCH2SCoAOCH3SCoAacetyl CoA coenzyme A HSCoAHSHSCoAHSCoACH2OCCOO–COO–CH2OOCCOO–COO–COO–CH2CH3Cnext cycle + Step 1 Step 2 Step 3 Step 4 Step 6 Step 7 Step 8 Step 5 citrate (6C) isocitrate (6C) succinyl CoA (4C)succinate (4C) fumarate (4C)
Cell_Biology_Alberts_442	Cell_Biology_Alberts	HSCoAHSHSCoAHSCoACH2OCCOO–COO–CH2OOCCOO–COO–COO–CH2CH3Cnext cycle + Step 1 Step 2 Step 3 Step 4 Step 6 Step 7 Step 8 Step 5 citrate (6C) isocitrate (6C) succinyl CoA (4C)succinate (4C) fumarate (4C) malate (4C) oxaloacetate (4C) oxaloacetate (4C) pyruvate ˜-ketoglutarate (5C) + H+ + H+ + H+ + H+ (2C) CITRIC ACID CYCLE Overview of the complete citric acid cycle. The two carbons from acetyl CoA that enter this turn of the cycle (shadowed in red ) will be converted to CO2 in subsequent turns of the cycle: it is the two carbons shadowed in blue that are converted to CO2 in this cycle. CGTPGDPNADHNADHNADHNAD+NAD+NAD+Pi FADFADH2Step 1 106 PaNel 2–9: The Complete Citric acid Cycle NADHNAD+ reaction, in which water is aconitaseadded back, moves the hydroxyl group from one carbon atom to its neighbor.	Cell_Biology_Alberts. HSCoAHSHSCoAHSCoACH2OCCOO–COO–CH2OOCCOO–COO–COO–CH2CH3Cnext cycle + Step 1 Step 2 Step 3 Step 4 Step 6 Step 7 Step 8 Step 5 citrate (6C) isocitrate (6C) succinyl CoA (4C)succinate (4C) fumarate (4C) malate (4C) oxaloacetate (4C) oxaloacetate (4C) pyruvate ˜-ketoglutarate (5C) + H+ + H+ + H+ + H+ (2C) CITRIC ACID CYCLE Overview of the complete citric acid cycle. The two carbons from acetyl CoA that enter this turn of the cycle (shadowed in red ) will be converted to CO2 in subsequent turns of the cycle: it is the two carbons shadowed in blue that are converted to CO2 in this cycle. CGTPGDPNADHNADHNADHNAD+NAD+NAD+Pi FADFADH2Step 1 106 PaNel 2–9: The Complete Citric acid Cycle NADHNAD+ reaction, in which water is aconitaseadded back, moves the hydroxyl group from one carbon atom to its neighbor.
Cell_Biology_Alberts_443	Cell_Biology_Alberts	In the frst of four oxidation steps in the cycle, the carbon carrying the hydroxyl group is converted to a carbonyl group. The immediate product is unstable, losing CO2 while still bound to the enzyme. The ˜-ketoglutarate dehydrogenase complex closely resembles the large enzyme complex that converts pyruvate to acetyl CoA, the pyruvate dehydrogenase complex in Figure 13–10. It likewise catalyzes an oxidation that produces NADH, CO2, and a high-energy thioester bond to coenzyme A (CoA). A phosphate molecule from solution displaces the CoA, forming a high-energy phosphate linkage to succinate. This phosphate is then passed to GDP to form GTP. (In bacteria and plants, ATP is formed instead.) In the third oxidation step in the cycle, FAD accepts two hydrogen atoms from succinate. The addition of water to fumarate places a hydroxyl group next to a carbonyl carbon. COO–COO–HOHHHHCCCisocitrate isocitrate dehydrogenase CO2COO–COO–COO–HHHOCCCoxalosuccinate intermediate COO–+ H+	Cell_Biology_Alberts. In the frst of four oxidation steps in the cycle, the carbon carrying the hydroxyl group is converted to a carbonyl group. The immediate product is unstable, losing CO2 while still bound to the enzyme. The ˜-ketoglutarate dehydrogenase complex closely resembles the large enzyme complex that converts pyruvate to acetyl CoA, the pyruvate dehydrogenase complex in Figure 13–10. It likewise catalyzes an oxidation that produces NADH, CO2, and a high-energy thioester bond to coenzyme A (CoA). A phosphate molecule from solution displaces the CoA, forming a high-energy phosphate linkage to succinate. This phosphate is then passed to GDP to form GTP. (In bacteria and plants, ATP is formed instead.) In the third oxidation step in the cycle, FAD accepts two hydrogen atoms from succinate. The addition of water to fumarate places a hydroxyl group next to a carbonyl carbon. COO–COO–HOHHHHCCCisocitrate isocitrate dehydrogenase CO2COO–COO–COO–HHHOCCCoxalosuccinate intermediate COO–+ H+
Cell_Biology_Alberts_444	Cell_Biology_Alberts	The addition of water to fumarate places a hydroxyl group next to a carbonyl carbon. COO–COO–HOHHHHCCCisocitrate isocitrate dehydrogenase CO2COO–COO–COO–HHHOCCCoxalosuccinate intermediate COO–+ H+ H+COO–COO–HHHHOCCC˜-ketoglutarate succinate dehydrogenase COO–COO–HHHHCCsuccinate COO–COO–HHCCfumarate fumarase COO–COO–HOHHHCCmalate COO–COO–HHCCfumarate H2O˜-ketoglutarate dehydrogenase complex CO2 + H+ COO–COO–HHHHOCCC˜-ketoglutarate COO–HHHHOCCCsuccinyl-CoA HSCoASCoA+ H2OCOO–HHHHOCCCsuccinyl-CoA SCoACOO–COO–HHHHCCsuccinate HSCoA+ succinyl-CoA synthetase GTPGDPFADNADHFADH2NAD+NADHNAD+Pi Step 3 Step 4 Step 5 Step 6 Step 7 107	Cell_Biology_Alberts. The addition of water to fumarate places a hydroxyl group next to a carbonyl carbon. COO–COO–HOHHHHCCCisocitrate isocitrate dehydrogenase CO2COO–COO–COO–HHHOCCCoxalosuccinate intermediate COO–+ H+ H+COO–COO–HHHHOCCC˜-ketoglutarate succinate dehydrogenase COO–COO–HHHHCCsuccinate COO–COO–HHCCfumarate fumarase COO–COO–HOHHHCCmalate COO–COO–HHCCfumarate H2O˜-ketoglutarate dehydrogenase complex CO2 + H+ COO–COO–HHHHOCCC˜-ketoglutarate COO–HHHHOCCCsuccinyl-CoA HSCoASCoA+ H2OCOO–HHHHOCCCsuccinyl-CoA SCoACOO–COO–HHHHCCsuccinate HSCoA+ succinyl-CoA synthetase GTPGDPFADNADHFADH2NAD+NADHNAD+Pi Step 3 Step 4 Step 5 Step 6 Step 7 107
Cell_Biology_Alberts_445	Cell_Biology_Alberts	Step 8 In the last of four malate dehydrogenaseoxidation steps in the cycle, the carbon carrying the hydroxyl group is converted to a carbonyl group, regenerating the oxaloacetate + H+ needed for step 1. COO– Berg Jm, Tymoczko Jl & stryer l (2011) Biochemistry, 7th ed. new York: Wh freeman. Garrett Rh & Grisham Cm (2012) Biochemistry, 5th ed. philadelphia: Thomson Brooks/Cole. moran la, horton hR, scrimgeour G & perry m (2011) principles of Biochemistry, 5th ed. Upper saddle River, nJ: prentice hall. nelson Dl & Cox mm (2012) lehninger principles of Biochemistry, 6th ed. new York: Worth. van holde Ke, Johnson WC & ho ps (2005) principles of physical Biochemistry, 2nd ed. Upper saddle River, nJ: prentice hall. Van Vranken D & Weiss G (2013) introduction to Bioorganic Chemistry and Chemical Biology. new York: Garland science. Voet D, Voet JG & pratt Cm (2012) fundamentals of Biochemistry, 4th ed. new York: Wiley.	Cell_Biology_Alberts. Step 8 In the last of four malate dehydrogenaseoxidation steps in the cycle, the carbon carrying the hydroxyl group is converted to a carbonyl group, regenerating the oxaloacetate + H+ needed for step 1. COO– Berg Jm, Tymoczko Jl & stryer l (2011) Biochemistry, 7th ed. new York: Wh freeman. Garrett Rh & Grisham Cm (2012) Biochemistry, 5th ed. philadelphia: Thomson Brooks/Cole. moran la, horton hR, scrimgeour G & perry m (2011) principles of Biochemistry, 5th ed. Upper saddle River, nJ: prentice hall. nelson Dl & Cox mm (2012) lehninger principles of Biochemistry, 6th ed. new York: Worth. van holde Ke, Johnson WC & ho ps (2005) principles of physical Biochemistry, 2nd ed. Upper saddle River, nJ: prentice hall. Van Vranken D & Weiss G (2013) introduction to Bioorganic Chemistry and Chemical Biology. new York: Garland science. Voet D, Voet JG & pratt Cm (2012) fundamentals of Biochemistry, 4th ed. new York: Wiley.
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