Xanthine oxidase activity in human tissues and its inhibition by allopurinol (4-hydroxypyrazolo[3,4-d] pyrimidine).

Abstract

Abstract A sensitive radiochemical method of measuring xanthine oxidase suitable for use with small amounts of crude tissue preparation in described. It depends on the enzymatic oxidation of xanthine-6- 14 C to 14 CO 2 by xanthine oxidase and uricase, under conditions where the rate of 14 CO 2 evolution is proportional to the amount of xanthine oxidase present. The xanthine oxidase activity of body fluids and tissues which are accessible to biopsy in the living human subject, and of some human necropsy tissues, have been determined. Only liver and small intestine mucosa contain more than a trace of xanthine oxidase activity. The method has also been used to assess xanthine dehydrogenase activity, to evaluate the Michaelis-Menten constant for the oxidation of xanthine by human small intestine xanthine oxidase (K M = 1.55 × 10 −5 M), and to study xanthine oxidase inhibition by allopurinol (4-hydroxypyrazolo [3, 4-d] pyrimidine) (Ki = 7.6 × 10 −9 M). Allopurinol inhibits the oxidation of hypoxanthine, as well as xanthine, by human small intestine mucosa xanthine oxidase.