The Metabolism of L-and D-histidine by Slices of Liver and Kidney*

Whether oxidative deamination is the favored initial step in the catabolism of histidine, as may be the case with many of the amino acids, is open to question. The supporting evidence of Krebs (1) is less striking with r,-histidine than with most other natural amino acids. Kidney slices yielded somewhat more ammonia in the presence of histidine and oxygen than in the absence of either, and liver slices produced small amounts of urea and ammonia, apparently at the expense of amino nitrogen and with a measurable oxygen uptake. According to Edlbacher and his associates (2) L-histidine is also attacked in the liver by histidase, an enzyme which leaves the or-amino group intact, but hydrolyzes the imidazole ring in such a way as to permit ultimate conversion of the histidine to glutamic acid. Like glutamic acid, L-histidine is glycogenic (3, 4). Production of urocanic acid from histidine by reductive cr-deamination has long been considered a possibility. Recently Edlbacher and Heitz (5) have isolated a hepatic enzyme (urocanicase) able to convert urocanic acid quantitatively to n-glutamic acid, presumably via isoglutamine, the a-carbon in this instance having its origin in the imidazole ring. That some oxidative or hydrolytic cr-deamination of histidine may occur seems likely. In the rat, imidazolelactic acid (6,7) and imidazolepyruvic acid (6) can serve as dietary substitutes for histidine, and n-histidine can be inverted to form the L isomer (8). Schoenheimer, Rittenberg, and Keston (9) noted that histidine isolated from the tissues of rats fed N16 as ammonia contained an excess of this isotope in its a-amino group. Without doubt n-histidine is less readily utilized than the natural isomer (4,8). It is said not to be attacked by histidase (2). According to Krebs (1) it is deaminized in the liver and kidney by n-amino acid oxidase. This has not been substantiated by tests with the reconstituted enzyme system. In such tests, Klein and Handler (10) observed only slow oxidation, Karrer and Frank (11) none.