TAILIEUCHUNG - Báo cáo khoa học: Mammalian xanthine oxidoreductase – mechanism of transition from xanthine dehydrogenase to xanthine oxidase

Reactive oxygen species are generated by various biological systems, including NADPH oxidases, xanthine oxidoreductase, and mitochondrial respiratory enzymes, and contribute to many physiological and pathologi-cal phenomena. | ễFEBS Journal REVIEW ARTICLE Mammalian xanthine oxidoreductase - mechanism of transition from xanthine dehydrogenase to xanthine oxidase Tomoko Nishino1 Ken Okamoto1 Bryan T. Eger2 Emil F. Pai2 and Takeshi Nishino1 1 Department of Biochemistry and Molecular Biology Nippon Medical School Tokyo Japan 2 Departments of Biochemistry MedicalBiophysics and Molecular Genetics University of Toronto and Division of Cancer Genomics Proteomics Ontario Cancer Institute University Health Network Toronto Canada Keywords p-cation interaction flavin semiquinone hydrogen peroxide iron-sulfur center molybdopterin cofactor reactive oxygen species superoxide xanthine dehydrogenase xanthine oxidase xanthine oxidoreductase Correspondence Takeshi Nishino Department of Biochemistry and Molecular Biology Nippon Medical School 1-1-5 Sendagi Bunkyo-ku Tokyo 113-8602 Japan Fax 81 3 5685 3054 Tel 81 3 3822 2131 E-mail nishino@ Reactive oxygen species are generated by various biological systems including NADPH oxidases xanthine oxidoreductase and mitochondrial respiratory enzymes and contribute to many physiological and pathological phenomena. Mammalian xanthine dehydrogenase XDH can be converted to xanthine oxidase XO which produces both superoxide anion and hydrogen peroxide. Recent X-ray crystallographic and site-directed mutagenesis studies have revealed a highly sophisticated mechanism of conversion from XDH to XO suggesting that the conversion is not a simple artefact but rather has a function in mammalian organisms. Furthermore this transition seems to involve a thermodynamic equilibrium between XDH and XO disulfide bond formation or proteolysis can then lock the enzyme in the XO form. In this review we focus on recent advances in our understanding of the mechanism of conversion from XDH to XO. Received 8 January 2008 revised 2 April 2008 accepted 28 April 2008 doi Introduction Xanthine oxidoreductase XOR catalyzes the oxidation of hypoxanthine to

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