Induction of Histidine-degrading Enzymes in Protein-starved Rats and Regulation of Histidine Metabolism

Inbred weanling rats were maintained on diets containing low (6%), medium (lS%), and high (40%) levels of proteins. After 45 days they were killed and the activities of histidine ammonia lyase, urocanase, and histidine pyruvate aminotransferase in liver were assayed. Histidine ammonia lyase increased with age of the rat, and the increase was proportional to the level of protein in the diet. Animals on a low protein diet surviving the feeding period had negligible histidine ammonia lyase activity. In contrast, epidermal histidine ammonia lyase decreased with the growth of the animals and was highest in the group on a low protein diet. Hepatic urocanase activity did not show significant changes during growth, but the levels of the enzymes in animals receiving a high protein diet were higher than in animals on a low protein diet. In contrast to histidine ammonia lyase and urocanase, histidine pyruvate aminotransferase levels changed neither with growth nor with the protein level of the diet. Induction of histidine ammonia lyase and urocanase could be demonstrated in protein-depleted adult rats by administering casein hydrolysate along with histidine by intubation. In a 24-hour forced feeding period, histidine ammonia lyase levels showed a 2-fold increase over the starting activity. The pattern of response of male and female rats to induction was similar. Induction was inhibited by ethionine. Concurrent administration of glucose with the inducer repressed the levels of histidine ammonia lyase. Up to 1 g of the enzymic digest of casein was required to bring about optimal activity of induction. However, 50 mg of the same digest were adequate for induction when fed along with 200 mg of L-histidine hydrochloride.