title: Suicide inactivation of xanthine oxidoreductase during reduction of inorganic nitrite to nitric oxide.
abstract: Xanthine oxidoreductase (XOR) is progressively inactivated while catalysing the reduction of inorganic nitrite to NO by xanthine. Inactivation results from conversion of the enzyme into its desulpho-form. The rate of inactivation increases with nitrite concentration. Similar behaviour was shown when NADH replaced xanthine as reducing substrate. A kinetic model is proposed incorporating a 'suicide' inactivation involving an enzyme-substrate (product) complex, rather than inactivation by free NO. The model provides a good fit to progress curves of the reaction of xanthine or NADH with nitrite in the presence of the oxidase or dehydrogenase forms of the enzyme. Inorganic nitrate, like nitrite, was shown to be reduced at the molybdenum site of XOR. With xanthine as reducing substrate, nitrite was produced in essentially a 1:1 stoichiometric ratio with respect to urate. Unlike the case of nitrite, the enzyme was not significantly inactivated, implying that inactivation during nitrite reduction depends on the presence of nascent NO in its enzyme complex.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: B L
authors.initials: BL
authors.lastname: Godber
authors.forename: J J
authors.initials: JJ
authors.lastname: Doel
authors.forename: T A
authors.initials: TA
authors.lastname: Goult
authors.forename: R
authors.initials: R
authors.lastname: Eisenthal
authors.forename: R
authors.initials: R
authors.lastname: Harrison
mesh_terms: D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D002417:Cattle; D007700:Kinetics; D008956:Models, Chemical; D008982:Molybdenum / Q000737:chemistry; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D010084:Oxidation-Reduction; D019820:Xanthine / Q000378:metabolism; D014968:Xanthine Dehydrogenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D009573:Nitrites; D019820:Xanthine; D009569:Nitric Oxide; D008982:Molybdenum; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase