Oxidation of hypoxanthines, bearing 8-aryl or 8-pyridyl substituents, by bovine milk xanthine oxidase.
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. 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. In 8-(3'-N-methylpyridinio)xanthine betaine, 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-methyl-8-(3'-N-methylpyridinio)-hypoxanthine betaine, which is not attacked in the pyrimidine ring. 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.
D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D002417:Cattle; D006863:Hydrogen-Ion Concentration; D007042:Hypoxanthines / Q000378:metabolism; D007700:Kinetics; D008892:Milk / Q000201:enzymology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D007042:Hypoxanthines; D000644:Quaternary Ammonium Compounds; D014969:Xanthine Oxidase