Xanthine dehydrogenase

Many cases of gout are successfully treated by the antimetabolite allopurinol, a structural analog of hypoxanthine in which the N7 and C8 positions are interchanged.

Xanthine dehydrogenase hydroxylates allopurinol at C2 (as it does hypoxanthine), giving alloxanthine, which remains tightly bound to the reduced form of the enzyme.

Allopurinol is thus a suicide substrate that strongly inhibits xanthine dehydrogenase.

This inhibition causes accumulation of hypoxanthine and xanthine, both of which are more soluble and, hence, more readily excreted than is uric acid.