Phosphoryl Group Transfers and ATP:- Other Phosphorylated Compounds and Thioesters Also Have Large Free Energies of Hydrolysis
Phosphoenolpyruvate (Fig. 13–3) contains a phosphate ester bond that undergoes hydrolysis to yield the enol form of pyruvate, and this direct product can immediately tautomerize to the more stable keto form of pyruvate. Because the reactant (phosphoenolpyruvate) has only one form (enol) and the product (pyruvate) has two possible forms, the product is stabilized relative to the reactant. This is the greatest contributing factor to the high standard free energy of hydrolysis of phospho enolpyruvate: ΔG0=-61.9 kJ/mol.
Another three-carbon compound, 1,3-bisphospho glycerate (Fig. 13–4), contains an anhydride bond between the carboxyl group at C-1 and phosphoric acid. Hydrolysis of this acyl phosphate is accompanied by a large, negative, standard free-energy change (ΔG0=- 49.3 kJ/mol), which can, again, be explained in terms of the structure of reactant and products. When H2O is added across the anhydride bond of 1,3-bisphospho glycerate, one of the direct products, 3-phosphoglyceric acid, can immediately lose a proton to give the carboxylate ion, 3-phosphoglycerate, which has two equally probable resonance forms (Fig. 13–4). Removal of the direct product (3-phosphoglyceric acid) and formation of the resonance-stabilized ion favor the forward reaction.
FIGURE 13–3 Hydrolysis of phosphoenol pyruvate (PEP). Catalyzed by pyruvate kinase, this reaction is followed by spontaneous tautomerization of the product, pyruvate. Tautomerization is not possible in PEP, and thus the products of hydrolysis are stabilized relative to the reactants. Resonance stabilization of Pi also occurs, as shown in Figure 13–1.
FIGURE 13–4 Hydrolysis of 1,3 bisphosphoglycerate. The direct product of hydrolysis is 3-phospho glyceric acid, with an undissociated carboxylic acid group, but dissociation occurs immediately. This ionization and the resonance structures it makes possible stabilize the product relative to the reactants. Resonance stabilization of Pi further contributes to the negative free energy change.
In phosphocreatine (Fig. 13–5), the PON bond can be hydrolyzed to generate free creatine and Pi. The re lease of Pi and the resonance stabilization of creatine favor the forward reaction. The standard free-energy change of phosphocreatine hydrolysis is again large, -43.0 kJ/mol.
In all these phosphate-releasing reactions, the several resonance forms available to Pi (Fig. 13–1) stabilize this product relative to the reactant, contributing to an already negative free-energy change. Table 13–6 lists the standard free energies of hydrolysis for a number of phosphorylated compounds. Thioesters, in which a sulfur atom replaces the usual oxygen in the ester bond, also have large, negative, standard free energies of hydrolysis. Acetyl-coenzyme A, or acetyl-CoA (Fig. 13–6), is one of many thioesters important in metabolism. The acyl group in these compounds is activated for transacylation, condensation, or oxidation-reduction reactions. Thioesters undergo much less resonance stabilization than do oxy gen esters; consequently, the difference in free energy between the reactant and its hydrolysis products, which are resonance-stabilized, is greater for thioesters than for comparable oxygen esters (Fig. 13–7). In both cases, hydrolysis of the ester generates a carboxylic acid, which can ionize and assume several resonance forms. Together, these factors result in the large, negative G (-31 kJ/mol) for acetyl-CoA hydrolysis. To summarize, for hydrolysis reactions with large, negative, standard free-energy changes, the products are more stable than the reactants for one or more of the following reasons: (1) the bond strain in reactants due to electrostatic repulsion is relieved by charge separation, as for ATP; (2) the products are stabilized by
FIGURE 13–5 Hydrolysis of phospho creatine. Breakage of the PON bond in phosphocreatine produces creatine, which is stabilized by formation of a resonance hybrid. The other product, Pi, is also resonance stabilized.
FIGURE 13–6 Hydrolysis of acetyl-coenzyme A. Acetyl-CoA is a thioester with a large, negative, standard free energy of hydrolysis. Thioesters contain a sulfur atom in the position occupied by an oxy gen atom in oxygen esters. The complete structure of coenzyme A (CoA, or CoASH) is shown in Figure 8–41.
ionization, as for ATP, acyl phosphates, and thioesters; (3) the products are stabilized by isomerization (tautomerization), as for phosphoenolpyruvate; and/or (4) the products are stabilized by resonance, as for creatine released from phosphocreatine, carboxylate ion released from acyl phosphates and thioesters, and phosphate (Pi) released from anhydride or ester linkages.
