Oxidation of hypoxanthines, bearing 8-aryl or 8-pyridyl substituents, by bovine milk xanthine oxidase

Abstract

1. 1.|Hypoxanthines, bearing at position 8 aryl or pyridyl substituents, are converted by bovine milk xanthine oxidase (xanthine: oxygen oxidoreductase, EC 1.2.3.2) into the corresponding xanthines at low rates. Oxidation is accelerated considerably when the 8-pyridyl substituents are quaternised. 2. 2.|In the enzymic oxidation of quaternary 8-pyridylhypoxanthines a lag phase precedes the attainment of a constant, maximal reaction rate. It is assumed that the delay is due to a relatively slow conformational change in the active enzymic center. 3. 3.|In 8-(3′- N-methylpyridinio)xanthine bethane, also the pyridinium moiety is attacked at high pH (9–11) to yield an N-methyl-2-pyridone. The analogous pyridone is the only oxidation product of 1-ethyl-8-(3′- N-methylpyridinio)hypoxanthine betaine, which is not attacked in the pyrimidine ring. 4. 4.|The cationic substrates are attracted to the enzyme by an anionic group, which probably forms an ion pair with a protonated amino group in or near the active center.