Hippuric acid, synthesis

Coenzyme A has recently been implicated in the activation and transfer of acyl groups other than acetate. For example, CoA is required for the oxidative decarboxylation of a-ketoglutarate to form succinate (Kaufman, 1951 Sanadi and Littlefield, 1951). Succinyl-CoA was proposed as an intermediate in this reaction. Hippuric acid synthesis also requires CoA (Chantrenne, 1951). The postulated intermediate in this case was benzoyl-CoA. The formation of acyl-CoA complexes from acetyl-CoA and free fatty acids may also occur (Stadtman, 1950, 1951). 

Protein Turnover in Liver 586 Some Aspects of Amino Acid Metabolism 587 Hippuric Acid Synthesis Cholate Synthesis Amino Acid Acetylation T ransmethylation... 

Chantrenne (59) and Schachter and Taggert (60) have demonstrated that hippuric-acid synthesis is the result of a similar reaction between benzoyl-SCoA and glycine. Finally, extracts of C. kluyveri contain an enzyme system that catalyzes the acylation of various amino acids and amines (61, 62). Again acyl-SCoA derivatives are the acyl donors. The latter reactions are, however, unique in that they do not occur in the absence of relatively high concentrations of HCN. As yet the role of HCN is undetermined. 

The key to the mechanism of the reaction came from Chantrenne s discovery that Coenzyme A as well as ATP is needed for hippuric acid synthesis.He also found that benzoylphosphate was unable to replace benzoic acid plus ATP, thus excluding benzoylphosphate as an intermediate. On the basis of known reactions and interactions of ATP, Co A, and acyl groups it appears that the reaction mechanism is... 

Inhibitor Glutamo-amide transfer Synthesis of hippuric acid or of p-amino-hippuric acid Synthesis of glutathione Amino acid Synthesis incor-of serum poraton albumin ... 

The requirement of coenzyme A for hippuric acid synthesis may be taken as evidence for a benzoyl-coenzyme A complex, similar to the acetyl-coenzyme A compound for which good evidence has been obtained. It is possible that coenzyme A-amino acid addition products are the real intermediates in protein synthesis, rather than the acyl phosphates shown in equation 37. 

---