Participation of Xanthine Oxidase in the Activation of Liver Tryptophan Pyrrolase

Xanthine oxidase appears to be the endogenous activating agent of inactive holotryptophan pyrrolase. Injection of 4-hydroxypyrazolo[3,4-d]pyrimidine (allopurinol), a competitive inhibitor of xanthine oxidase, in control, hydrocortisone-treated, or tryptophan-treated rats is followed by inhibition of the activity of tryptophan pyrrolase in whole liver homogenates and high speed supernatants. This inhibition is not caused by a direct effect on tryptophan pyrrolase, because allopurinol does not inhibit the activity or conjugation with its prosthetic group in purified preparations of tryptophan pyrrolase. Nor is the synthesis de novo of tryptophan pyrrolase caused by hydrocortisone impaired by allopurinol. Furthermore, removal of xanthine oxidase from high speed liver supernatants by addition of homologous antibody is followed by a loss of activation of the inactive holotryptophan pyrrolase by purines. The degree of activation of the inactive enzyme by purines is dependent upon the level of xanthine oxidase activity. Because this activation by purines is not dependent upon addition of hemoglobin, the xanthine oxidase is apparently activating the inactive holoenzyme.