The regulation of tryptophan pyrrolase activity by tryptophan

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Abstract

Tryptophan pyrrolase accumulates in the livers of hydrocortisone-treated rats as the inactive apoenzyme. Treatment with tryptophan activates the apoenzyme by conjugating it with hematin and permitting its conversion to the active, reduced holoenzyme form of tryptophan pyrrolase. The same activation reactions occur in vitro and in vivo. They require l-tryptophan in the concentrations which are operative in vivo. The rate of degradation of tryptophan in the rat is proportional to the amount of the reduced holoenzyme present in the liver. Thus the chemical, biochemical and physiological conditions are appropriate for tryptophan to regulate its own metabolism by activating the enzyme which oxidizes it. This regulation by activation is combined with regulation of the amount of enzyme by induction, and together these constitute a vital mechanism. The enzyme in intact animals given tryptophan is induced by endogenously released glucocorticoids as well as by tryptophan, the apoenzyme formed is activated, the tryptophan is degraded, and the initial state is restored. This hierarchy of regulation fails in adrenalectomized rats, who lack the hormonal induction mechanism. The enzyme formed, though active, is insufficient to dispose of the tryptophan, and the rats die.

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