Acetylation of Optical Isomers of S-benzylcysteine in Rats and Humans

Abstract

We reported the conversion of S-benzyl-l-cysteine to the corresponding acetyl derivative in the rat, rabbit, dog and man and suggested the possibility of the inversion of S-benzyl-d-cysteine to the acetylated l-derivative via Knoop's acetylation mechanism which postulates the formation of a keto acid from the d-amino acid followed by the interaction of the keto acid with ammonia and pyruvic acid to give the l-acetyl amino acid. duVigneaud, et al., reported results which apparently indicated such an inversion of S-benzyl-d-cysteine in the rat. On feeding the d-isomer to rats, some l-acetyl derivative together with dl-acetyl benzylcysteine were isolated from the urine. When d-benzylcysteine was fed to rats and humans, significantly smaller yields of the acetylated products could be isolated from the urine as compared to those obtained after the administration of comparable amounts of l-benzylcysteine. We drew the conclusion at the time that these findings did not conform to the postulates of Knoop's acetylation theory which presupposes that if the acetylation of an amino acid takes place via the keto acid, then the amounts of the acetylated product excreted in the urine of animals which were fed d- or l- amino acid should be the same. Indeed, du Vigneaud and Irish, who revived Knoop's theory, stated that “this would be expected if the theory were correct, since both enantiomorphs should be deaminated to the keto acid.” The lower yields of the acetyl derivatives in the urine after the feeding of d-benzylcysteine to rats and man we later attributed to a possible destruction of the intermediate keto acid which was presumably formed from d-benzyl-cysteine prior to its conversion to the acetyl derivative.