The Functional Significance of Changes in Activity of the Enzymes, Tryptophan Pyrrolase and Tyrosine Transaminase, after Induction in Intact Rats and in the Isolated, Perfused Rat Liver

Abstract

Abstract The possible functional significance of induction of the hepatic enzymes, tryptophan pyrrolase and tyrosine transaminase, has been studied in intact normal and adrenalectomized adult male rats and in the isolated perfused rat liver. In intact, normal rats, several-fold increases in tryptophan pyrrolase activity induced by treatment with hydrocortisone or tryptophan, or both, were associated with at most a 20% increase in the percentage dose of dl-tryptophan-3-14C converted to 14CO2. However, under conditions in which the activity of tryptophan pyrrolase did not increase further, for example, with increasing the tryptophan load from 17.5 to 35 mg, the conversion of labeled tryptophan to 14CO2 was substantially increased. In the adrenalectomized rat, hydrocortisone elicited a 6-fold increase in tryptophan pyrrolase activity without changing oxidation of a tracer dose of dl-tryptophan-3-14C to 14CO2. Although hydrocortisone added to the labeled tryptophan load led to a further 4-fold increase in tryptophan pyrrolase activity, no change in oxidation of tryptophan to 14CO2 was seen. In the adrenalectomized rat the percentage dose l-tyrosine-1-14C converted to 14CO2 increased substantially with a 10-mg or 30-mg load of l-tyrosine in spite of the fact that the level of hepatic tyrosine transaminase remains unchanged; in contrast, treatment with hydrocortisone leads to a 7- to 14-fold increase of enzyme activity, yet the increase in oxidation of l-tyrosine-1-14C to 14CO2 is trivial at several load levels. In the isolated perfused rat liver induction of tryptophan pyrrolase with hydrocortisone did not alter the rate of clearance of a graded load of l-tryptophan from the perfusate, did not enhance accumulation of kynurenine in the perfusate, and did not increase the rate of conversion of dl-tryptophan-3-14C to 14CO2. Thus, manifold increases in enzyme activity inducible in the intact or adrenalectomized rat and in the isolated perfused liver are not associated with parallel increases in oxidation of 14C-labeled amino acids to 14CO2. However, increasing the substrate load per se was associated with quantitatively large increases in oxidation to 14CO2 under conditions not associated with altered levels of enzyme activity.