The synthesis of S-benzylthiopyruvic acid and its conversion to N-acetyl-S-benzyl-L-cysteine in the rat; unavailability of thiopyruvic acid to rats for growth purposes.

Some time ago we demonstrated the acetylation of S-benzyl-L-cysteine in the dog, rabbit, rat, and man (l-3). Administration of S-benzyl-ncysteine to rats (4, 5) or man (3) was followed by the excretion of some N-acetyl-S-benzyl-L-cysteine, thus indicating a partial inversion of the D derivative of cysteine to the optical antipode. Ample experimental evidence is available to show that oxidative deamination of n-amino acids occurs in vivo and in vitro. In an attempt to explain the inversion of Sbenzyl-D-cysteine in viva, it has been postulated that S-benzylthiopyruvic acid is formed in vivo as the intermediate (2-5). S-Benzyl-L-cysteine is readily deaminated oxidatively by rat kidney preparations (6), and a hydrazone of a keto acid has been isolated from rabbit urine following the administration of S-benzyl-L-cysteine, which was presumably the hydrazone of S-benzylthiopyruvic acid (7). Previous experiments have shown that the cr-hydroxy analogues of S-benzyl-nand S-benzyl-DL-cysteine are excreted unchanged by the rat, suggesting that the rat is unable to oxidize the hydroxy acid or to aminate it (8). In the present study we prepared S-benzylthiopyruvic acid and administered it to adult rats. From the urine of these animals we isolated N-acetyl-S-benzyl-L-cysteine and identified it in a conventional manner. The demonstration of the asymmetric synthesis of L-cysteine derivative from the corresponding keto acid raised the question of a similar synthesis of L-cysteine from thiopyruvic acid in vivo. It will be recalled from earlier studies that n-cystine could not replace L-cystine in the diet of the rat for growth purposes (9)) although n-cystine was shown to undergo ready oxidative deamination in vitro by rat kidney preparations (10). It thus appeared possible that n-cystine undergoes oxidative deamination in vivo also, but the resulting thiopyruvic acid is metabolized before the synthesis of Lcystine can occur. It should be pointed out, however, that in studies on