Peptide and keto acid utilization in replacing phenylalanine in adaptive enzyme synthesis.

Glycylasparagine has been found to be more effective than aspartic acid in reversing the inhibition of adaptive enzyme synthesis by cysteic acid or P-hydroxyaspartic acid or combinations of these synergistic inhibitors (1). The results were interpreted to indicate a pathway of utilization of the peptide not involving the inhibited enzymatic utilization of the free amino acid. Also, histidine peptides have been reported to be more effective than histidine in stimulating production of tetanus toxin (2). However, most reports concerning peptides and keto acids have involved growth experiments which have indicated in general that keto acids as well as peptides can perform essential functions for which they are utilized in some cases more effectively than the corresponding amino acids (3-10). Certain peptides and keto acids are antagonized by their specific analogues more effectively than by the corresponding free amino acid analogue (6, 7). Growth data, in many instances, do not permit a definite conclusion as to whether the separate routes of utilization of peptides and keto acids involve protein synthesis or essential functions of these compounds other than protein synthesis. A study of peptide and keto acid utilization in adaptive enzyme formation affords a more direct approach to this problem. The present investigation involves a study of the inhibitory effects of thienyl analogues on the utilization of phenylpyruvic acid and of peptides of phenylalanine in replacing phenylalanine in the synthesis of the adaptive malic enzyme in Lactobacillus arabinosus. The results indicate that peptides and the keto acid of phenylalanine are utilized for enzyme synthesis by routes which do not involve an essential site of utilization of phenylalanine.