《生物化学原理》（英文版）BIOENERGETICS AND METABOLISM

Part l Bioenergetics and Metabolism decarboxylations(as in the acetoacetate decarboxylase electrons results in isomerization, transposition of dou- eaction; see Fig 17-18). Entire metabolic pathways are ble bonds, or cis-trans rearrangements of double bonds organized around the introduction of a carbonyl group An example of isomerization is the formation of fruc in a particular location so that a nearby carbon-carbon tose 6-phosphate from glucose 6-phosphate during bond can be formed or cleaved. In some reactions, this sugar metabolism(Fig ga; this reaction is discussed in sle is played by an imine group or a specialized cofac. detail in Chapter 14). Carbon-l is reduced(from alde- tor such as pyridoxal phosphate, rather than by a car- hyde to alcohol) and C-2 is oxidized(from alcohol to bonyl group ketone). Figure 9b shows the details of the electron movements that result in isomerization 3. Internal rearrangements, isomerizations, and eliminations A simple transposition of a C=C bond occurs dur- Another common type of cellular reaction is an in- ing metabolism of the common fatty acid oleic acid(see tramolecular rearrangement, in which redistribution of Fig 17-9), and you will encounter some spectacular ex amples of double-bond repositioning in the synthesis of cholesterol(see Fig 21-35) Elimination of water introduces a c=c bond be. tween two carbons that previously were saturated (as in the enolase reaction; see Fig 6-23). Similar reactions can result in the elimination of alcohols and amines Po (b-C-C H OH o R2 Roh R2 4. Group transfer reactions The transfer of acyl, glycosyl, and phosphoryl groups from one nucleophile to another is common in living cells. Acyl group transfer generally involves the addition of a nucleophile to the carbonyl OH R1H O H RI carbon of an acyl group to form a tetrahedral interme- CoAS-C-C:→C=0 CoA-S Claisen ester condensation R-C-X 一R-C-C-H+co Y Tetrahedral Decarboxylation of a B-keto acid The chymotrypsin reaction is one example of acyl group transfer(see Fig. 6-21). Glycosyl group transfers in- 8 Carbon-carbon bond formation reactions. (a)The carbon volve nucleophilic substitution at C-1 of a sugar ring. carbonyl group is an electrophile by virtue of the electron- which is the central atom of an acetal. In principle, the awing capacity of the electronegative oxygen atom, which results substitution could proceed by an SNl or SN2 path, in a resonance hybrid structure in which the carbon has a partial pos- described for the enzyme lysozyme(see Fig. 6-25) itive charge.(b)Within a molecule, delocalization of electrons into a Phosphoryl group transfers play a special role in carbonyl group facilitates the transient formation of a carbanion on an metabolic pathways. A general theme in metabolism is adjacent carbon (c)Some of the major reactions involved in the for mation and breakage of C-c bonds in biological systems. For both the the attachment of a god Idol condensation and the claisen condensation a carbanion serves intermediate to "activate"the intermediate for subse- as nucleophile and the carbon of a carbonyl group serves as elec. quent reaction. Among the better leaving groups in rophile. The carbanion is stabilized in each case by another carbony nucleophilic substitution reactions are inorganic or at the carbon adjoining the carbanion carbon. In the decarboxylation thophosphate(the ionized form of H PO, at neutral pH, leaves. The reaction would not occur at an appreciable rate but for Pi) and inorganic pyrophosphate(P207, abbreviated the stabilizing effect of the carbonyl adjacent to the carbanion car. PP); esters and anhydrides of phosphoric acid are bon. Wherever a carbanion is shown, a stabilizing resonance with the effectively activated for reaction. Nucleophilic substi- adjacent carbonyl, as shown in(a), is assumed. The formation of the tution is made more favorable by the attachment of a carbanion is highly disfavored unless the stabilizing carbonyl group, phosphoryl group to an otherwise poor leaving group or a group of similar function such such as-OH. Nucleophilic substitutions in which th

decarboxylations (as in the acetoacetate decarboxylase reaction; see Fig. 17–18). Entire metabolic pathways are organized around the introduction of a carbonyl group in a particular location so that a nearby carbon–carbon bond can be formed or cleaved. In some reactions, this role is played by an imine group or a specialized cofac￾tor such as pyridoxal phosphate, rather than by a car￾bonyl group. 3. Internal rearrangements, isomerizations, and eliminations Another common type of cellular reaction is an in￾tramolecular rearrangement, in which redistribution of electrons results in isomerization, transposition of dou￾ble bonds, or cis-trans rearrangements of double bonds. An example of isomerization is the formation of fruc￾tose 6-phosphate from glucose 6-phosphate during sugar metabolism (Fig 9a; this reaction is discussed in detail in Chapter 14). Carbon-1 is reduced (from alde￾hyde to alcohol) and C-2 is oxidized (from alcohol to ketone). Figure 9b shows the details of the electron movements that result in isomerization. A simple transposition of a CUC bond occurs dur￾ing metabolism of the common fatty acid oleic acid (see Fig. 17–9), and you will encounter some spectacular ex￾amples of double-bond repositioning in the synthesis of cholesterol (see Fig. 21–35). Elimination of water introduces a CUC bond be￾tween two carbons that previously were saturated (as in the enolase reaction; see Fig. 6–23). Similar reactions can result in the elimination of alcohols and amines. 4. Group transfer reactions The transfer of acyl, glycosyl, and phosphoryl groups from one nucleophile to another is common in living cells. Acyl group transfer generally involves the addition of a nucleophile to the carbonyl carbon of an acyl group to form a tetrahedral interme￾diate. The chymotrypsin reaction is one example of acyl group transfer (see Fig. 6–21). Glycosyl group transfers in￾volve nucleophilic substitution at C-1 of a sugar ring, which is the central atom of an acetal. In principle, the substitution could proceed by an SN1 or SN2 path, as described for the enzyme lysozyme (see Fig. 6–25). Phosphoryl group transfers play a special role in metabolic pathways. A general theme in metabolism is the attachment of a good leaving group to a metabolic intermediate to “activate” the intermediate for subse￾quent reaction. Among the better leaving groups in nucleophilic substitution reactions are inorganic or￾thophosphate (the ionized form of H3PO4 at neutral pH, a mixture of H2PO4  and HPO4 2, commonly abbreviated Pi ) and inorganic pyrophosphate (P2O7 4, abbreviated PPi ); esters and anhydrides of phosphoric acid are effectively activated for reaction. Nucleophilic substi￾tution is made more favorable by the attachment of a phosphoryl group to an otherwise poor leaving group such as OOH. Nucleophilic substitutions in which the R C Tetrahedral intermediate O Y X R C O Y X R C O Y X R C C H H OH R1 H2O H H C H2O H R C R1 486 Part II Bioenergetics and Metabolism C C C C C
(a) (b) (c) O
 O O  R1 C Aldol condensation C O R2 H C R3 R4 O H R1 C C O R2 H C R3 R4 OH CoA-S C Claisen ester condensation C O H H C R1 R2 O H CoA-S C C O H H C R1 R2 OH R C Decarboxylation of a -keto acid C O H H C O O H R C C O H H H CO2  FIGURE 8 Carbon–carbon bond formation reactions. (a) The carbon atom of a carbonyl group is an electrophile by virtue of the electron￾withdrawing capacity of the electronegative oxygen atom, which results in a resonance hybrid structure in which the carbon has a partial pos￾itive charge. (b) Within a molecule, delocalization of electrons into a carbonyl group facilitates the transient formation of a carbanion on an adjacent carbon. (c) Some of the major reactions involved in the for￾mation and breakage of COC bonds in biological systems. For both the aldol condensation and the Claisen condensation, a carbanion serves as nucleophile and the carbon of a carbonyl group serves as elec￾trophile. The carbanion is stabilized in each case by another carbonyl at the carbon adjoining the carbanion carbon. In the decarboxylation reaction, a carbanion is formed on the carbon shaded blue as the CO2 leaves. The reaction would not occur at an appreciable rate but for the stabilizing effect of the carbonyl adjacent to the carbanion car￾bon. Wherever a carbanion is shown, a stabilizing resonance with the adjacent carbonyl, as shown in (a), is assumed. The formation of the carbanion is highly disfavored unless the stabilizing carbonyl group, or a group of similar function such as an imine, is present.

Part l Bioenergetics and Metabolism H OHH HH OHH H-C-2C--C-C-C-C-0-P-o H--C-C-C-C-C-C-0-P- O H OHOHH OH O H OHoHH O Glucose 6-pho Fructose 6-phosphate H H② This allows t a c-hbo formation of a C=C o by B B, abstracts a proton, allawi H the hydrogen ion aC=O bond. donated by b FIGURE 9 Isomerization and elimination reactions.(a) The conver- rows represent the movement of bonding electrons from nucleophile sion of glucose 6-phosphate to fructose 6-phosphate, a reaction of(pink] to electrophile(blue). B, and B2 are basic groups on the sugar metabolism catalyzed by phosphohexose isomerase(b)This re. enzyme: they are capable of donating and accepting hydrogen ions action proceeds through an enediol intermediate. The curved blue ar.(protons)as the reaction progresses. phosphoryl group (P03")serves as a leaving group charge and can therefore act as an electrophile. Ina very occur in hundreds of metabolic reactions large number of metabolic reactions, a phosphoryl group Phosphorus can form five covalent bonds. The con-(P03)is transferred from atP to an alcohol(form- ventional representation of Pi( Fig. 10a), with three ing a phosphate ester)(Fig. 10c)or to a carboxylic acid P-O bonds and one P=0 bond, is not an accurate pic- (forming a mixed anhydride). When a nucleophile at ture.In P. four equivalent phosphorus-oxygen bonds tacks the electrophilic phosphorus atom in ATP, a rela share some double-bond character, and the anion has a tively stable pentacovalent structure is formed as a re tetrahedral structure( Fig. 10b). As oxygen is more elec- action intermediate (Fig. 10d). With departure of the tronegative than phosphorus, the sharing of electrons is leaving group (ADP), the transfer of a phosphoryl group unequal: the central phosphorus bears a partial positive complete. The large family of enzymes that catalyze o-P=0 O-P-0 Adenine HRiboseF0-P-0-P-0-P-0 HO-R ATP 0→P-0 O=P-0- Adenine H Ribose 0-P-0-P-0+-0-P-0-R Glucose 6-phosphate. Z---P--w Z=R-OH FIGURE 10 Altermative ways of showing the structure of inorganic all four phosphorus-oxygen bonds with some double-bond character; orthophosphate (a) In one(inadequate)representation, three oxygens the hybrid orbitals so represented are arranged in a tetrahedron with are single- bonded to phosphorus, and the fourth is double -bonded, P at its center. (c)When a nucleophile Z (in this case, the-OH on allowing the four different resonance structures shown. (b)The four C-o of glucose)attacks ATP, it displaces ADP (W). In this SN2 reac. resonance structures can be represented more accurately by showing tion, a pentacovalent intermediate(d) forms transiently

phosphoryl group (OPO3 2) serves as a leaving group occur in hundreds of metabolic reactions. Phosphorus can form five covalent bonds. The con￾ventional representation of Pi (Fig. 10a), with three POO bonds and one PUO bond, is not an accurate pic￾ture. In Pi , four equivalent phosphorus–oxygen bonds share some double-bond character, and the anion has a tetrahedral structure (Fig. 10b). As oxygen is more elec￾tronegative than phosphorus, the sharing of electrons is unequal: the central phosphorus bears a partial positive charge and can therefore act as an electrophile. In a very large number of metabolic reactions, a phosphoryl group (OPO3 2) is transferred from ATP to an alcohol (form￾ing a phosphate ester) (Fig. 10c) or to a carboxylic acid (forming a mixed anhydride). When a nucleophile at￾tacks the electrophilic phosphorus atom in ATP, a rela￾tively stable pentacovalent structure is formed as a re￾action intermediate (Fig. 10d). With departure of the leaving group (ADP), the transfer of a phosphoryl group is complete. The large family of enzymes that catalyze Part II Bioenergetics and Metabolism 487 H 1 C 2 C B1 H O OH Glucose 6-phosphate B2 H C C H O OH C OH H C H OH C H OH C H H O P O O O H 1 C 2 C OH O Fructose 6-phosphate Enediol intermediate H C OH H C H OH C H OH C H H O P O O O (a) (b) phosphohexose isomerase 1 B1 abstracts a proton. 4 B2 abstracts a proton, allowing the formation of a C 2 This allows the formation of a C double bond. 3 Electrons from carbonyl form an 5 An electron leaves the C the hydrogen ion donated by B2. C C O bond. C bond to form a O H bond with C H bond with the proton donated by B1. B1 H H C H O O H C OH H C O B1 B2 B2 rows represent the movement of bonding electrons from nucleophile (pink) to electrophile (blue). B1 and B2 are basic groups on the enzyme; they are capable of donating and accepting hydrogen ions (protons) as the reaction progresses. FIGURE 9 Isomerization and elimination reactions. (a) The conver￾sion of glucose 6-phosphate to fructose 6-phosphate, a reaction of sugar metabolism catalyzed by phosphohexose isomerase. (b) This re￾action proceeds through an enediol intermediate. The curved blue ar￾O P O O O O O O P O O O P O O O O O O P O O O 3 O P (a) (b) O P O O O O O O Z P W (d) (c) Adenine Ribose O O P O P O HO R O P O O O O O Glucose ATP Adenine Ribose O O P O  O O P O  O P R O O O O ADP Glucose 6-phosphate, a phosphate ester Z  R OH W  ADP FIGURE 10 Alternative ways of showing the structure of inorganic orthophosphate. (a) In one (inadequate) representation, three oxygens are single-bonded to phosphorus, and the fourth is double-bonded, allowing the four different resonance structures shown. (b) The four resonance structures can be represented more accurately by showing all four phosphorus–oxygen bonds with some double-bond character; the hybrid orbitals so represented are arranged in a tetrahedron with P at its center. (c) When a nucleophile Z (in this case, the OOH on C-6 of glucose) attacks ATP, it displaces ADP (W). In this SN2 reac￾tion, a pentacovalent intermediate (d) forms transiently.

Part l Bioenergetics and Metabolism phosphoryl group transfers with ATP as donor are called chemiosmotic energy coupling, a universal mechanism kinases(Greek kinein. " to move"). Hexokinase, for ex- in which a transmembrane electrochemical potential ample, "moves"a phosphoryl group from ATP to glucose. produced either by substrate oxidation or by light ab- Phosphoryl groups are not the only activators of this sorption, drives the synthesis of ATP type. Thioalcohols(thiols), in which the oxygen atom Chapters 20 through 22 describe the major anabolic of an alcohol is replaced with a sulfur atom, are also pathways by which cells use the energy in atP to pro- good leaving groups. Thiols activate carboxylic acids by duce carbohydrates, lipids, amino acids, and nucleotides forming thioesters(thiol esters)with them. We will dis- from simpler precursors. In Chapter 23 we step back cuss a number of cases, including the reactions cat- from our detailed look at the metabolic pathways-as alyzed by the fatty acyl transferases in lipid synthesis they occur in all organisms, from Escherichia coli to (see Fig 21-2), in which nucleophilic substitution at the humans-and consider how they are regulated and in carbonyl carbon of a thioester results in transfer of the tegrated in mammals by hormonal mechanisms. acyl group to another moiety As we undertake our study of intermediary metab olism, a final word. Keep in mind that the myriad re- 5. Free radical reactions Once thought to be rare, the actions described in these pages take place in, and play homolytic cleavage of covalent bonds to generate free crucial roles in, living organisms. As you encounter each adicals has now been found in a range of biochemical reaction and each pathway ask, What does this chemi processes. Some examples are the reactions of methyl- cal transformation do for the organism? How does this malonyl-CoA mutase(see Box 17-2), ribonucleotide pathway interconnect with the other pathways operat- reductase(see Fig. 22-41), and DNa photolyase(see ing simultaneously in the same cell to produce the en Fig25-25) ergy and products required for cell maintenance and growth? How do the multilayered regulatory mecha- We begin Part II with a discussion of the basic en- nisms cooperate to balance metabolic and energy in- ergetic principles that govern all metabolism( Chapter puts and outputs, achieving the dynamic steady state 13). We then consider the major catabolic pathways by of life? Studied with this perspective, metabolism pro which cells obtain energy from the oxidation of various vides fascinating and revealing insights into life, with fuels( Chapters 14 through 19). Chapter 19 is the piv- countless applications in medicine, agriculture, and otal point of our discussion of metabolism; it concerns biotechnology

phosphoryl group transfers with ATP as donor are called kinases (Greek kinein, “to move”). Hexokinase, for ex￾ample, “moves” a phosphoryl group from ATP to glucose. Phosphoryl groups are not the only activators of this type. Thioalcohols (thiols), in which the oxygen atom of an alcohol is replaced with a sulfur atom, are also good leaving groups. Thiols activate carboxylic acids by forming thioesters (thiol esters) with them. We will dis￾cuss a number of cases, including the reactions cat￾alyzed by the fatty acyl transferases in lipid synthesis (see Fig. 21–2), in which nucleophilic substitution at the carbonyl carbon of a thioester results in transfer of the acyl group to another moiety. 5. Free radical reactions Once thought to be rare, the homolytic cleavage of covalent bonds to generate free radicals has now been found in a range of biochemical processes. Some examples are the reactions of methyl￾malonyl-CoA mutase (see Box 17–2), ribonucleotide reductase (see Fig. 22–41), and DNA photolyase (see Fig. 25–25). We begin Part II with a discussion of the basic en￾ergetic principles that govern all metabolism (Chapter 13). We then consider the major catabolic pathways by which cells obtain energy from the oxidation of various fuels (Chapters 14 through 19). Chapter 19 is the piv￾otal point of our discussion of metabolism; it concerns chemiosmotic energy coupling, a universal mechanism in which a transmembrane electrochemical potential, produced either by substrate oxidation or by light ab￾sorption, drives the synthesis of ATP. Chapters 20 through 22 describe the major anabolic pathways by which cells use the energy in ATP to pro￾duce carbohydrates, lipids, amino acids, and nucleotides from simpler precursors. In Chapter 23 we step back from our detailed look at the metabolic pathways—as they occur in all organisms, from Escherichia coli to humans—and consider how they are regulated and in￾tegrated in mammals by hormonal mechanisms. As we undertake our study of intermediary metab￾olism, a final word. Keep in mind that the myriad re￾actions described in these pages take place in, and play crucial roles in, living organisms. As you encounter each reaction and each pathway ask, What does this chemi￾cal transformation do for the organism? How does this pathway interconnect with the other pathways operat￾ing simultaneously in the same cell to produce the en￾ergy and products required for cell maintenance and growth? How do the multilayered regulatory mecha￾nisms cooperate to balance metabolic and energy in￾puts and outputs, achieving the dynamic steady state of life? Studied with this perspective, metabolism pro￾vides fascinating and revealing insights into life, with countless applications in medicine, agriculture, and biotechnology. 488 Part II Bioenergetics and Metabolism

chapter PRINCIPLES OF BIOENERGETICS 13.1 Bioenergetics and Thermodynamics 490 heat and that this process of 13.2 Phosphoryl Group Transfers and AIP 496 respiration is essential to life He observed that 13.3 Biological Oxidation-Reduction Reactions 507 in general, respiration The total energy of the universe is constant; the total bustion of carbon and hy entropy is continually increasing drogen, which is entirely -Rudolf Clausius, The Mechanical Theory of Heat with Its similar to that which oc- m-Engine and to the Physic urs in a lighted lamp or Properties of Bodies, 1865(trans. 1867) candle, and that, from this int of view. animals that respire are true com- 1743-1794 The isomorphism of entropy and information establishes a bustible bodies that burn link between the two forms of power: the power to do and and consume themselves.. One may say that this the power to direct what is done analogy between combustion and respiration has francois Jacob, La logique du vivant: une histoire de Iheredite not escaped the notice of the poets, or rather (The Logic of Life: A History of Heredity), 1970 philosophers of antiquity, and which they had heaven, this torch of Prometheus, does not only rep sent an ingenious and poetic idea, it is a faithful picture of the operations of nature, at least for an ness energy and to channel it into biological work is a imals that breathe: one may therefore say, with the fundamental property of all living organisms; it must ancients, that the torch of life lights itself at the mo- have been acquired very early in cellular evolution. Mod ment the infant breathes for the first time. and it ern organisms carry out a remarkable variety of energy does not extinguish itself except at death. transductions, conversions of one form of energy to an- In this century, biochemical studies have revealed other. They use the chemical energy in fuels to bring much of the chemistry underlying that"torch of life about the synthesis of complex, highly ordered macro- Biological energy transductions obey the same physical molecules from simple precursors. They also convert the laws that govern all other natural processes. It is there. chemical energy of fuels into concentration gradients fore essential for a student of biochemistry to under- and electrical gradients, into motion and heat, and, in a stand these laws and how they apply to the flow of few organisms such as fireflies and some deep-sea fish, energy in the biosphere. In this chapter we first review to light. Photosynthetic organisms transduce light en. the laws of thermodynamics and the quantitative rela- ergy into all these other forms of energy The chemical mechanisms that underlie biologica tionships among free energy, enthalpy, and entropy. We hen describe the special role of ATP in biologi energy transductions have fascinated and challenged Mlogists for centuries. Antoine Lavoisier, before he lost his head in the French Revolution, recognized that an- avoisier,a( 1862)Oeuvres de lavoisier, imals somehow transform chemical fuels(foods) into Imperiale,Paris

chapter Living cells and organisms must perform work to stay alive, to grow, and to reproduce. The ability to har￾ness energy and to channel it into biological work is a fundamental property of all living organisms; it must have been acquired very early in cellular evolution. Mod￾ern organisms carry out a remarkable variety of energy transductions, conversions of one form of energy to an￾other. They use the chemical energy in fuels to bring about the synthesis of complex, highly ordered macro￾molecules from simple precursors. They also convert the chemical energy of fuels into concentration gradients and electrical gradients, into motion and heat, and, in a few organisms such as fireflies and some deep-sea fish, into light. Photosynthetic organisms transduce light en￾ergy into all these other forms of energy. The chemical mechanisms that underlie biological energy transductions have fascinated and challenged biologists for centuries. Antoine Lavoisier, before he lost his head in the French Revolution, recognized that an￾imals somehow transform chemical fuels (foods) into heat and that this process of respiration is essential to life. He observed that ... in general, respiration is nothing but a slow com￾bustion of carbon and hy￾drogen, which is entirely similar to that which oc￾curs in a lighted lamp or candle, and that, from this point of view, animals that respire are true com￾bustible bodies that burn and consume themselves . . . One may say that this analogy between combustion and respiration has not escaped the notice of the poets, or rather the philosophers of antiquity, and which they had ex￾pounded and interpreted. This fire stolen from heaven, this torch of Prometheus, does not only rep￾resent an ingenious and poetic idea, it is a faithful picture of the operations of nature, at least for an￾imals that breathe; one may therefore say, with the ancients, that the torch of life lights itself at the mo￾ment the infant breathes for the first time, and it does not extinguish itself except at death.* In this century, biochemical studies have revealed much of the chemistry underlying that “torch of life.” Biological energy transductions obey the same physical laws that govern all other natural processes. It is there￾fore essential for a student of biochemistry to under￾stand these laws and how they apply to the flow of energy in the biosphere. In this chapter we first review the laws of thermodynamics and the quantitative rela￾tionships among free energy, enthalpy, and entropy. We then describe the special role of ATP in biological PRINCIPLES OF BIOENERGETICS 13.1 Bioenergetics and Thermodynamics 490 13.2 Phosphoryl Group Transfers and ATP 496 13.3 Biological Oxidation-Reduction Reactions 507 The total energy of the universe is constant; the total entropy is continually increasing. —Rudolf Clausius, The Mechanical Theory of Heat with Its Applications to the Steam-Engine and to the Physical Properties of Bodies, 1865 (trans. 1867) The isomorphism of entropy and information establishes a link between the two forms of power: the power to do and the power to direct what is done. —François Jacob, La logique du vivant: une histoire de l’hérédité (The Logic of Life: A History of Heredity), 1970 13 489 *From a memoir by Armand Seguin and Antoine Lavoisier, dated 1789, quoted in Lavoisier, A. (1862) Oeuvres de Lavoisier, Imprimerie Impériale, Paris. Antoine Lavoisier, 1743–1794

490 Chapter 13 Principles of Bioenergetics energy exchanges. Finally, we consider the importance not violate the second law, they operate strictly within of oxidation-reduction reactions in living cells, the en- it. To discuss the application of the second law to bio rgetics of electron-transfer reactions, and the electron logical systems, we must first define those systems and carriers commonly employed as cofactors of the en- their surroundings zymes that catalyze these reactions The reacting system is the collection of matter that is undergoing a particular chemical or physical process: it may be an organism, a cell, or two reacting com- 13.1 Bioenergetics and Thermodynamics pounds. The reacting system and its surroundings to- gether constitute the universe. In the laboratory, some Bioenergetics is the quantitative study of the energy chemical or physical processes can be carried out in iso transductions that occur in living cells and of the nature lated or closed systems, in which no material or energy and function of the chemical processes underlying these is exchanged with the surroundings. Living cells and or- modynamics have been introduced in earlier chapters material and energy with their surroundings: living sys- and the constant transactions between system and sur- Biological Energy Transformations Obey the Laws roundings explain how organisms can create order within themselves while operating within the second law of Thermodynamics of thermodynamics Many quantitative observations made by physicists and In Chapter 1(p. 23)we defined three thermody chemists on the interconversion of different forms of namic quantities that describe the energy changes oc energy led, in the nineteenth century. to the formula- curring in a chemical reaction tion of two fundamental laws of thermodynamics. The first law is the principle of the conservation of energy. Gibbs free energy, G, expresses the amount of for any physical or chemical change, the tota energy capable of doing work during a reaction amount of energy in the universe remains constant, at constant temperature and pressure. When a energy may change form or it may be transported reaction proceeds with the release of free energy from one region to another, but it cannot be created (that is, when the system changes so as to or destroyed. The second law of thermodynamics, which possess less free energy), the free-energy change, can be stated in several forms, says that the universe AG, has a negative value and the reaction is said always tends toward increasing disorder: in all natu- exergonIc endergonic reactions, the ral processes, the entropy of the universe increases. system gains free energy and AG is positive Living organisms consist of collections of molecules Enthalpy, H, is the heat content of the reacting much more highly organized than the surrounding ma system. It reflects the number and kinds of terials from which they are constructed, and organisms chemical bonds in the reactants and products. maintain and produce order, seemingly oblivious to the When a chemical reaction releases heat, it is second law of thermodynamics. But living organisms do said to be exothermic. the heat content of the products is less than that of the reactants an AHhas, by convention, a negative value. Reacting systems that take up heat from their surroundings are endothermic and have positive values of AH. Entropy, S, is a quantitative expression for the randomness or disorder in a system(see Box 1-3) When the products of a reaction are less complex and more disordered than the reactants the reaction is said to proceed with a gain in entropy. The units of AG and aH are joules/mole or calories/mole (recall that 1 cal= 4.184 J); units of entropy ar joules/mole. Kelvin(J/mol K)(Table 13-1) Under the conditions existing in biological systen (including constant temperature and pressure changes in free energy, enthalpy, and entropy are re- "Now, in the second law of thermodynamics lated to each other quantitatively by the equation △G=△H-TAS (13-1)

energy exchanges. Finally, we consider the importance of oxidation-reduction reactions in living cells, the en￾ergetics of electron-transfer reactions, and the electron carriers commonly employed as cofactors of the en￾zymes that catalyze these reactions. 13.1 Bioenergetics and Thermodynamics Bioenergetics is the quantitative study of the energy transductions that occur in living cells and of the nature and function of the chemical processes underlying these transductions. Although many of the principles of ther￾modynamics have been introduced in earlier chapters and may be familiar to you, a review of the quantitative aspects of these principles is useful here. Biological Energy Transformations Obey the Laws of Thermodynamics Many quantitative observations made by physicists and chemists on the interconversion of different forms of energy led, in the nineteenth century, to the formula￾tion of two fundamental laws of thermodynamics. The first law is the principle of the conservation of energy: for any physical or chemical change, the total amount of energy in the universe remains constant; energy may change form or it may be transported from one region to another, but it cannot be created or destroyed. The second law of thermodynamics, which can be stated in several forms, says that the universe always tends toward increasing disorder: in all natu￾ral processes, the entropy of the universe increases. Living organisms consist of collections of molecules much more highly organized than the surrounding ma￾terials from which they are constructed, and organisms maintain and produce order, seemingly oblivious to the second law of thermodynamics. But living organisms do not violate the second law; they operate strictly within it. To discuss the application of the second law to bio￾logical systems, we must first define those systems and their surroundings. The reacting system is the collection of matter that is undergoing a particular chemical or physical process; it may be an organism, a cell, or two reacting com￾pounds. The reacting system and its surroundings to￾gether constitute the universe. In the laboratory, some chemical or physical processes can be carried out in iso￾lated or closed systems, in which no material or energy is exchanged with the surroundings. Living cells and or￾ganisms, however, are open systems, exchanging both material and energy with their surroundings; living sys￾tems are never at equilibrium with their surroundings, and the constant transactions between system and sur￾roundings explain how organisms can create order within themselves while operating within the second law of thermodynamics. In Chapter 1 (p. 23) we defined three thermody￾namic quantities that describe the energy changes oc￾curring in a chemical reaction: Gibbs free energy, G, expresses the amount of energy capable of doing work during a reaction at constant temperature and pressure. When a reaction proceeds with the release of free energy (that is, when the system changes so as to possess less free energy), the free-energy change, G, has a negative value and the reaction is said to be exergonic. In endergonic reactions, the system gains free energy and G is positive. Enthalpy, H, is the heat content of the reacting system. It reflects the number and kinds of chemical bonds in the reactants and products. When a chemical reaction releases heat, it is said to be exothermic; the heat content of the products is less than that of the reactants and H has, by convention, a negative value. Reacting systems that take up heat from their surroundings are endothermic and have positive values of H. Entropy, S, is a quantitative expression for the randomness or disorder in a system (see Box 1–3). When the products of a reaction are less complex and more disordered than the reactants, the reaction is said to proceed with a gain in entropy. The units of G and H are joules/mole or calories/mole (recall that 1 cal  4.184 J); units of entropy are joules/mole  Kelvin (J/mol  K) (Table 13–1). Under the conditions existing in biological systems (including constant temperature and pressure), changes in free energy, enthalpy, and entropy are re￾lated to each other quantitatively by the equation G  H  T S (13–1) 490 Chapter 13 Principles of Bioenergetics