The activation and induction of tryptophan pyrrolase during experimental porphyria and by amino-triazole

The administration of a porphyria causing agent, allylisopropylacetamide, to intact or adrenalectomized rats results in four- and two-fold increases in the level of liver tryptophan pyrrolase. Administration of 3-amino-1,2,4-triazole to adrenalectomized rats causes a similar change in the level of liver tryptophan pyrrolase. The induction of the enzyme by both compounds is associated with its activation, presumably due to an increased availability of the endogenous iron-protoporphyrin activator of the enzyme. Thus, these results, together with the previously observed mechanism of substrate induction, suggest that the process of activation of tryptophan pyrrolase may be the stimulus for its induction. Liver tryptophan pyrrolase from 3-amino-1,2,4-triazole-treated rats need be assayed in the absence of fresh microsomes since the latter seem to catalyze the formation of a metabolite of 3-amino-1,2,4-triazole which inhibits the activity of tryptophan pyrrolase.