title: Xanthine oxidase converts nitric oxide to nitroxyl that inactivates the enzyme.
abstract: Xanthine oxidase (XO) was found to convert nitric oxide (NO* ) released from spermine-NONOate to nitroxyl (HNO), the one-electron reduction product of NO*, in the presence of its substrate hypoxanthine under anaerobic conditions. Under these conditions, XO lost its activity. Upon aerobic incubation of XO with its substrate, neither conversion of NO* to HNO nor inactivation of the enzyme was observed. Angeli's salt (an HNO generator) or synthetic peroxynitrite inactivated XO at low concentrations, whereas high concentrations of diethylamine-NONOate (an NO* donor) and SIN-1 (which generates peroxynitrite by releasing both NO* and superoxide) were required to inactivate XO. These results suggest that HNO generated by XO under anaerobic conditions inactivates XO. As both XO and NO* synthase are activated and/or induced in ischemia-reperfusion injury, HNO formed by XO may contribute to pathogenesis by exerting its potent oxidation activity against a variety of biological compounds.
authors.affiliation: International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Saleem
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohshima
mesh_terms: D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D006454:Hemoglobins / Q000737:chemistry; D008981:Molsidomine / Q000031:analogs & derivatives / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000737:chemistry; D009589:Nitrogen Oxides / Q000737:chemistry*; D010100:Oxygen / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000737:chemistry; D011485:Protein Binding; D026361:Reactive Nitrogen Species; D013096:Spermine / Q000737:chemistry; D019820:Xanthine / Q000737:chemistry; D014969:Xanthine Oxidase / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
chemical_list: D006454:Hemoglobins; D009573:Nitrites; D009589:Nitrogen Oxides; D026361:Reactive Nitrogen Species; C008657:nitrosyl hemoglobin; D030421:Peroxynitrous Acid; D019820:Xanthine; D013096:Spermine; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D014969:Xanthine Oxidase; C039900:nitroxyl; D010100:Oxygen