4 Обмен энергией (1160073), страница 6
Текст из файла (страница 6)
We can easily calculate AGP. For example, in human erythrocytes the concentrationsof ATP, ADP, and Pj are 2.25, 0.25, and 1.65 HIM,respectively (Table 13-5). Let us assume for simplicity that the pH is 7.0 and the temperature is25 °C, the standard pH and temperature. The actual free energy of hydrolysis of ATP in the erythrocyte under these conditions is given by the relationshipAG = AG°' +RT In[ADPKPJ[ATP]Substituting the appropriate values we obtainAG = -30,500 J/mol + (8.315 J/mol • KX298 K)(2.50 x JQ-4)(1.65 x 1Q-3)In2.25 x 10-3= -30,500 J/mol + (2,480 J/mol) In (1.83 x 10~4)= -30,500 J/mol - 21,300 J/mol = -51,800 J/mol= -51.8kJ/molTable 13-5 Adenine nucleotide, inorganic phosphate, andphosphocreatine concentrations in some cells*Concentration (HIM)Rat hepatocyteRat myocyteHuman erythrocyteRat neuronE. coli cell375ATPADPAMP3.388.052.252.597.901.320.930.250.731.040.290.040.020.060.82PiPCr4.802804.708.051.652.727.9* For erythrocytes the concentrations are those of the cytosol (human erythrocytes lack a nucleusand mitochondria).
In the other types of cells the data are for the entire cell contents, althoughthe cytosol and the mitochondria have very different concentrations of ADP. Phosphocreatine(PCr) is discussed later in this chapter.Thus AGP, the actual free-energy change for ATPhydrolysis in the intact erythrocyte (-51.8 kJ/mol),is much larger than the standard free-energychange (-30.5 kJ/mol). By the same token, the freeenergy required to synthesize ATP from ADP andPi under the conditions prevailing in the erythrocyte would be 51.8 kJ/mol.Because the concentrations of ATP, ADP, and Pimay differ from one cell type to another (Table 135), AGP for ATP hydrolysis likewise differs.
Moreover, in any given cell AGP can vary from time totime, depending on the metabolic conditions in thecell and how they influence the concentrations ofATP, ADP, Pi, and H + (pH). We can calculate theactual free-energy change for any given metabolicreaction as it occurs in the cell, providing we knowthe concentrations of all the reactants and products of the reaction and other factors (such as pH,temperature, and the concentration of Mg2+) thatmay affect the equilibrium constant and thus thefree-energy change.378Part III Bioenergetics and MetabolismTo summarize, compounds with large, negative, standard free energies of hydrolysis give products that are more stable than the reactantsbecause of one or more of the following: (1) the bond strain in reactantsdue to electrostatic repulsion is relieved by charge separation, as in thecase of ATP (described earlier), (2) the products are stabilized by ionization, as in the case of ATP, acyl phosphates, and thioesters, (3) theproducts are stabilized by isomerization (tautomerization), as for phosphoenolpyruvate, and/or (4) the products are stabilized by resonance,as for creatine from phosphocreatine, the carboxylate ion from acylphosphates and thioesters, and phosphate (Pi) from all of the phosphorylated compounds.ATP Provides Energy by Group Transfers,Not by Simple HydrolysisFigure 13-8 The contribution of ATP to a reactionis often shown with a single arrow (a), but is almost always a two-step process, such as that shownhere for the reaction catalyzed by ATP-dependentglutamine synthetase (b).Throughout this book we will refer to reactions or processes for whichATP supplies energy, and the contribution of ATP to these reactionswill commonly be indicated as in Figure 13-8a, with a single arrowshowing the conversion of ATP into ADP and Pi? or of ATP into AMPand PPi (pyrophosphate).
When written this way, these reactions ofATP appear to be simple hydrolysis reactions in which water displaceseither Pi or PPi, and one is tempted to say that an ATP-dependentreaction is "driven by the hydrolysis of ATP." This is not the case. ATPhydrolysis per se usually accomplishes nothing but the liberation ofheat, which cannot drive a chemical process in an isothermal system.Single reaction arrows such as those in Figure 13-8a almost invariably represent two-step processes (Fig.
13-8b) in which part of theATP molecule, either a phosphoryl group or the adenylate moiety(AMP), is first transferred to a substrate molecule or to an amino acidresidue in an enzyme, becoming covalently attached to and raising thefree-energy content of the substrate or enzyme. In the second step, thephosphate-containing moiety transferred in the first step is displaced,COO"H 3 N-CHCOO"ATPADP + PiH.N-CH(a) Written as aone-step reactionGlutamate(b) Actual reactionhas two steps©Enzyme-boundglutamyl phosphateChapter 13 Principles of Bioenergeticsgenerating either P^ or AMP. Thus ATP participates in the enzymecatalyzed reaction to which it contributes free energy. There is oneimportant class of exceptions to this generalization: those processes inwhich noncovalent binding of ATP (or of GTP), followed by its hydrolysis to ADP and Pi? provides the energy to cycle a protein between twoconformations, producing mechanical motion, as in muscle contractionor in the movement of enzymes along DNA (discussed below).The phosphate compounds found in living organisms can be divided arbitrarily into two groups, based on their standard free energiesof hydrolysis (Fig.
13-9). "High-energy" compounds have a AG°' of hydrolysis more negative than -25kJ/mol; "low-energy" compoundshave a less negative AG°'. ATP, for which AG°' of hydrolysis is-30.5 kJ/mol (-7.3 kcal/mol), is a high-energy compound; glucose-6phosphate, with a standard free energy of hydrolysis of -13.8 kJ/mol(-3.3 kcal/mol), is a low-energy compound.The term "high-energy phosphate bond," although long used bybiochemists, is incorrect and misleading, as it wrongly suggests thatthe bond itself contains the energy. In fact, the breaking of chemicalbonds requires an input of energy. The free energy released by hydrolysis of phosphate compounds thus does not come from the specific bondthat is broken but results from the products of the reaction having asmaller free-energy content than the reactants. For simplicity, we willsometimes use the term "high-energy phosphate compound" when referring to ATP or other phosphate compounds with a large, negative,standard free energy of hydrolysis.From the additivity of free-energy changes of sequential reactions,one can see that the synthesis of any phosphorylated compound can beaccomplished by coupling it to the breakdown of another phosphorylated compound with a more negative free energy of hydrolysis (Fig.13-9).
One can therefore describe phosphorylated compounds as having a high or low phosphate group transfer potential. The phosphate group transfer potential of phosphoenolpyruvate is very high,that of ATP is high, and that of glucose-6-phosphate is low.Figure 13—9 Flow of phosphate groups, represented by (P), from high-energy phosphate donorsvia ATP to acceptor molecules (such as glucose andglycerol) to form their low-energy phosphate derivatives. This flow of phosphate groups, which is catalyzed by enzymes called kinases, proceeds with anoverall loss of free energy under intracellular conditions. Hydrolysis of low-energy phosphate compounds releases Pi5 which has an even lower grouptransfer potential.-70COO"C—O—(P) Phosphoenolpyruvate-60-50c3-40CHOHCH 2 -O-(P)1,3-Bisphosphoglycerate-30High-energycompoundsLow-energycompounds-20 -Glucose-6-(P)-10 PiGlycerol-(P)379380Part III Bioenergetics and MetabolismMuch of catabolism is directed toward the synthesis of high-energyphosphate compounds, but their formation is not an end in itself; it isthe means of activating a very wide variety of compounds for furtherchemical transformation.
The transfer of a phosphoryl group to a compound effectively puts free energy into that compound, so that it hasmore free energy to give up during subsequent metabolic transformations. We described above how the synthesis of glucose-6-phosphate isaccomplished by phosphoryl group transfer from ATP. We shall see inthe next chapter that this phosphorylation of glucose activates or"primes" the glucose for catabolic reactions that occur in nearly everyliving cell.In some reactions that involve ATP, both of its terminal phosphategroups are released in one piece as PPi. Simultaneously, the remainderof the ATP molecule (adenylate) is joined to another compound, whichis thereby activated.
For example, the first step in the activation of afatty acid either for energy-yielding oxidation (Chapter 16) or for use inthe synthesis of more complex lipids (Chapter 20) is its attachment tothe carrier coenzyme A (Fig. 13-10). The direct condensation of a fattyacid with coenzyme A is endergonic, but the formation of fatty acylCoA is made exergonic by coupling it to the net breakdown, in twosteps, of ATP.0oFigure 13-10 Both phosphoric acid anhydridebonds in ATP are eventually broken in the formation of palmitoyl-coenzyme A.
In the first step ofthe reaction, ATP donates adenylate (AMP), forming the fatty acyl adenylate and releasing PPj. Thepyrophosphate is subsequently hydrolyzed by inorganic pyrophosphatase. The "energized" fatty acylgroup is then transferred to coenzyme A.CH3(CH2)i4—C00+ O —P—O —P—O—P—O— Rib — Adenine°"OOPalmitate0ATP2P,OOCH 3 (CH 2 ) 14 -CO---P-O—Rib —Adenine0Palmitoyl adenylate- CoASHCoenzyme AOCH 3 (CH 2 ) 14 -CS CoAPalmitoyl-CoAO+ O P O—Rib — AdenineOAMPOverall reaction:Palmitate + ATP + CoASH> palmitoyl-CoA + AMP + 2P,AG°' = -32.5 kJ/molChapter 13 Principles of Bioenergetics381In the first step, adenylate (AMP) is transferred from ATP to thecarboxyl group of the fatty acid, forming a mixed anhydride (fatty acyladenylate) and liberating PPi.
In the second step, the thiol group ofcoenzyme A displaces the adenylate group and forms a thioester withthe fatty acid. The sum of these two reactions is the exergonic hydrolysis of ATP to AMP and PPi (AGO/ = -32.2 kJ/mol) and the endergonicformation of fatty acyl-CoA (AGO/ = 31.4 kJ/mol).The formation of fatty acyl-CoA is made energetically favorable bya third step, in which the PPi formed in the first step is hydrolyzed bythe ubiquitous enzyme inorganic pyrophosphatase to yield 2 ^ :H2O2PiAG0' = -33.4kJ/molRNAchainThus, in the activation of a fatty acid, both of the phosphoric acid anhydride bonds of ATP are broken. The resulting AGO/ is the sum of theAG°' values for the breakage of these bonds:ATP + 2H2OAMP + 2PjAGO/ - -65.6 kJ/molThe activation of amino acids before their polymerization into proteins (Chapter 26) is accomplished by an analogous set of reactions.
![](https://s.studizba.com/z.php?f=/templates/si/i/noavatar.png&w=100&h=100&t=1"){kind=avatar}
