Biochemistry - The Chemical Reactions of Living Cells, Volume 2 - D. Metzler 1980

Types of enzyme-catalyzed reactions
Multiple displacement reactions and the coupling of ATP cleavage with endergonic processes
Acyl phosphates

The transfer of a phosphoryl or adenylyl group from ATP to the oxygen atom of a carboxyl group yields an acyl phosphate—a metabolite of exceptional biological importance:

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In acyl phosphates, both the acyl and phosphoryl residues possess a high group transfer potential. Consequently, acyl phosphates can serve as intermediate metabolites through which the group transfer potential of an ATP molecule is transmitted to other molecules to drive chemical work.

A typical example of coupling ATP Hydrolysis with a synthesis reaction involving The formation of an acyl phosphate is the synthesis of acetyl-CoA (see also Chapter 8, Section B):

Since the acetyl group in the product of this reaction also features a high group transfer potential, the ∆G' for this reaction has a large positive value; hence, the spontaneous Formation of Acetyl-CoA will not occur.

At the same time, the sum of the standard free-energy changes for reaction (7-27) and the ATP hydrolysis reaction (7-28) is approximately zero (0.6 kJ/mol):

The coupling of these two reactions is achieved via a specialized mechanism in which, During the first stage [stage a in equation (7-29)], the oxygen atom of the nucleophilic carboxyl group attacks the P_y atom of the ATP molecule to yield acetylphosphate, while In the second stage (stage b), the sulfur atom of the —SH group of coenzyme A attacks the carbon atom of acetylphosphate, displacing P_i, which is an excellent leaving group. Although the ∆G' for stage a is quite high (meaning that acetylphosphate will be produced in relatively low concentrations unless the [ATP]/[ADP] ratio becomes high), at equilibrium, stage b is strongly driven toward product formation.

The two reactions of equation (7-29) are catalyzed by acetate kinase and S-acetyltransferase, respectively. This reaction sequence represents a crucial initial step in the utilization of acetate required for bacterial growth. In some Bacteria, this sequence operates in reverse to generate

ATP during Fermentation. Conversely, in most Eukaryotic Cells, acetyl-CoA is synthesized from acetate by coupling acetyl-CoA synthesis with the Cleavage of ATP to AMP and P_i. Both stages of equation (7-30) are catalyzed by the same enzyme—acetate-thiokinase.

This reaction sequence is identical to sequence (7-29) with the sole exception that the initial displacement occurs at the P_a atom of the ATP molecule, leading to the formation of acetyl adenylate. This intermediate remains tightly bound to the enzyme until the Second Stage of the reaction sequence takes place. It has been demonstrated that the ¹⁸O of the acetate molecule [indicated by an asterisk in equation (7-30)] is incorporated into the phosphate group of AMP, which is fully consistent with the proposed mechanism.