THE INHIBITION OF TRYPTOPHAN PYRROLASE BY ALLOPURINOL, AN INHIBITOR OF XANTHINE OXIDASE

Abstract

The effect of allopurinol (4-hydroxypyrazolo(3,4-d)pyrimidine) on tryptophan pyrrolase activity of rats and mice was determined. After a single intraperitoneal injection of allopurinol at levels equal to or slightly greater than those given orally for the treatment of gout in humans, the drug was found to be an inhibitor of tryptophan pyrrolase activity. After injection of allopurinol, rats excreted significantly less kynurenine, but the drug did not alter plasma tryptophan levels. A study was made of the in vitro inhibition of tryptophan pyrrolase by allopurinol. The drug was found to be a very potent noncompetitive inhibitor of tryptophan pyrrolase with a K_i value of 8 × 10⁻⁷ M. Allopurinol at 1.5 × 10⁻⁶ M concentration inhibited the enzyme 50%.