Biomaterial Database

Oxypurinol as an inhibitor of xanthine oxidase-catalyzed production of superoxide radical. 1988

T Spector

Wellcome Research Laboratories, Research Triangle Park, NC 27709.

A recent study of the mechanism by which oxypurinol inhibits uric acid generation [T. Spector, W. W. Hall and T. A. Krenitsky, Biochem. Pharmac. 35, 3109(1986)] showed that xanthine is ineffective in impeding the binding of oxypurinol to reduced xanthine oxidase. This study prompted the present hypothesis that, at elevated concentrations of substrates, oxypurinol would be superior to allopurinol as an inhibitor of the xanthine oxidase-catalyzed production of superoxide radical. It was found that the potency of allopurinol was attenuated by elevated concentrations of xanthine and hypoxanthine, whereas the potency of oxypurinol was relatively unaffected. Oxypurinol produced immediate inhibition of superoxide radical production as well as progressive inhibition with time. In contrast, allopurinol, which is also a substrate for xanthine oxidase, produced very little immediate inhibition and caused progressive inhibition only after conversion to oxypurinol. The theoretical advantages of treating ischemic tissues with oxypurinol are discussed.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D010117	Oxypurinol	A xanthine oxidase inhibitor.	Alloxanthine,Oxipurinol
D011743	Pyrimidines	A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D000493	Allopurinol	A XANTHINE OXIDASE inhibitor that decreases URIC ACID production. It also acts as an antimetabolite on some simpler organisms.	Allohexal,Allohexan,Alloprin,Allopurin,Allorin,Allpargin,Allural,Apulonga,Apurin,Atisuril,Bleminol,Caplenal,Capurate,Cellidrin,Embarin,Foligan,Hamarin,Jenapurinol,Lopurin,Lysuron,Milurit,Milurite,Novopurol,Pan Quimica,Progout,Pureduct,Purinol,Remid,Rimapurinol,Roucol,Suspendol,Tipuric,Uribenz,Uridocid,Uripurinol,Urosin,Urtias,Xanthomax,Xanturic,Zygout,Zyloprim,Zyloric
D013481	Superoxides	Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.	Superoxide Radical,Superoxide,Superoxide Anion
D014969	Xanthine Oxidase	An iron-molybdenum flavoprotein containing FLAVIN-ADENINE DINUCLEOTIDE that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria.	Hypoxanthine Oxidase,Hypoxanthine Dehydrogenase,Hypoxanthine-Xanthine Oxidase,Purine-Xanthine Oxidase,Dehydrogenase, Hypoxanthine,Hypoxanthine Xanthine Oxidase,Oxidase, Hypoxanthine,Oxidase, Hypoxanthine-Xanthine,Oxidase, Purine-Xanthine,Oxidase, Xanthine,Purine Xanthine Oxidase