Effect of colchicine and allopurinol on uricogenesis. I. Kinetics of their inhibitory action on hepatic xanthine dehydrogenase

Abstract

The inhibition induced by colchicine on chicken lixer xanthinedehydrogenase is of a reversible type, whereas allopurinol inhibits the enzyme pseudoirreversibly.

Xanthine and allopurinol compete for the same active site of the enzyme, so that the substrato xanthine protects the dehydrogenase from the inhibitor, apparent Ki = 8X X 10-t M. The interaction between allopurinol and the enzyme appears to satisfy a pseudofirst order kinetics. The second order constant found is 1.6 X 103 M-1 min-1. The relation between the inactivation rates and the concentration of inhibitor appears to be non rectilineal. The mechanism of the inhibitory action exerted by allopurinol upon chicken xanthinedehydrogenase, Km = 4X10"‘M, could be explained by the following sequence of reactions: E + I El (El).