Copyright © 2000-2003 Mark Brandt, Ph.D.7BioenergeticsCatabolism involves more than the simple breakdown of compounds. Combustion ofglucose yields large amounts of energy (∆G´° = –2870 kJ/mol for glucose conversionto carbon dioxide and water); however, most of this energy is released as heat.Metabolic processes occur in many steps to allow both the diversion of energy inusable form and the diversion of catabolic pathway intermediates for biosyntheticprocesses.One major method for diverting energy in usable form involves the use of “high-energy phosphate” compounds.High-energy phosphate compoundsPhosphate-containing compounds are considered “high-energy” if they have large–∆G° for hydrolysis (“large” meaning “more negative than –20 to –25 kJ/mol”).High-energy phosphate compounds are not used for long-term energy storage. Theyare temporary forms of stored energy, and are used to carry energy from onereaction to another.High-energy phosphate compounds are not necessarily unstable. Remember that∆G´° does not indicate anything about the rate of a reaction; most “high-energycompounds” are quite stable, because the hydrolysis reaction activation energy isquite large. In most cases, the conversion of a high-energy compound to a low-energy compound at detectable rates requires the intervention of an enzyme.Examples of high-energy compoundsOrganisms use a number of high-energy compounds. The following includes a fewexamples. The ∆G´° for the hydrolysis reaction are included for each reaction. Notethat, in most cases, the hydrolysis reaction as drawn rarely occurs in cells.One of these compounds deserves your special attention: ATP. Anyone studyingbiochemistry will become very familiar with ATP. ATP is an extremely usefulmolecule for exchanging energy between enzymes.The hydrolysis of ATP has a ∆G´° of –30.5 kJ/mol (note that the precise value issomewhat variable, depending on the presence of magnesium and other non-reactant species that alter the energetics of the reaction). In addition, because incells the concentration of ATP is typically considerably higher than that of ADP, the∆G for the reaction is more negative than the ∆G´° value. Recall that ∆G is ameasure of the amount of energy available to do work; ATP hydrolysis can thereforeCopyright © 2000-2003 Mark Brandt, Ph.D.8donate energy to other systems to allow those systems to perform reactions thatwould otherwise be thermodynamically unfavorable.Among phosphate-containing molecules, ATP has a central location. Although itcontains high-energy phosphate bonds, the energy in each of the ATPphosphoanhydride bonds is somewhat lower than the energy of a few otherbiological molecules.For example, the hydrolysis of phosphoenolpyruvate has a large negative ∆G´°, dueto the fact that the covalent bond to the phosphate traps pyruvate in the energeticenol configuration.Phosphoenolpyruvate has a much higher ∆G´° than ATP. In cells, the directhydrolysis of phosphoenolpyruvate does not occur; instead, the energy stored in thismolecule is transferred to ATP in a reaction catalyzed by the enzyme pyruvatekinase.In this case, the two reactions (i.e. the hydrolysis of phosphoenolpyruvate and thereverse of the hydrolysis of ATP) are coupled. The normally unfavorable reaction(the conversion of ADP + phosphate to ATP) becomes a spontaneous process.A second interesting reaction is:Note that the ∆G´° for phosphocreatine hydrolysis is also strongly negative. In cells,the reaction catalyzed by creatine kinase (below) is reversible (this reaction isimportant in muscle as a method for rapidly generating ATP under conditions ofrapid utilization; resting muscles replenish their supply of phosphocreatine usingthe right-to-left reaction).Copyright © 2000-2003 Mark Brandt, Ph.D.9The ∆G´° for the reaction is –12.8 kJ/mol. Note that this is the sum of the hydrolysis∆G´° values: –43.3 kJ/mol + 30.5 kJ/mol. For this calculation, the ADP conversion toATP is the reverse of the hydrolysis reaction, and therefore has a +∆G´°.If you consider the moderately large ∆G´° for the creatine kinase reaction, it issomewhat surprising that this reaction is reversible. Once again, however, it isnecessary to remember that ∆G´° does not determine whether a reaction isspontaneous. Instead, it is the ∆G for the reaction that determines whethera reaction is spontaneous. The normal concentration of ATP in the cell is muchhigher than the concentration of ADP. In resting cells, the relative concentrations ofADP and ATP are such that the ∆G for hydrolysis of ATP is about –50 kJ/mol.The creatine kinase reaction thus illustrates two important points. The first point isthat the actual physiological value of ∆G varies depending on the cellularconditions. Reactions may therefore be reversible or irreversible under cellularconditions, in spite of sizable ∆G´° values. The second point is that, formultisubstrate reactions, it is possible to couple a favorable reaction to anunfavorable one. When this is done, the overall ∆G´° is the sum of the ∆G´° for theindividual reactions (as shown above).The coupled reactions shown thus far involve the transfer of phosphate from onemolecule to another (or the hydrolysis of phosphate compounds). ATP is heavilyinvolved in these phosphate transfer reactions, and most kinase2 reactions use ATPas the phosphate donor.However, in some cases, cleavage of the high-energy bond is used entirely as adriving force, and the reaction does result in hydrolysis of the bond. Once again,ATP is the most commonly used energy source for these reactions. An example ofthis is the reaction catalyzed by the biotin-dependent enzyme pyruvate carboxylase.The product oxaloacetate does not contain a phosphate. Instead, thethermodynamically unfavorable addition of carbonate to the pyruvate is coupled tothe thermodynamically favorable ATP hydrolysis by the enzyme.ATP hydrolysis is also widely used by active transport pump proteins that move 2 A “kinase” is an enzyme that phosphorylates its substrate. The name of the enzyme usually comesfrom the phosphate acceptor. In some cases, confusion as to the physiological substrate results