EC 1.17.3.2

Reaction: xanthine + H₂O + O₂ = urate + H₂O₂

For diagram of reaction, click here

Glossary: 4-mercuribenzoate = (4-carboxylatophenyl)mercury

Other name(s): hypoxanthine oxidase; hypoxanthine:oxygen oxidoreductase; Schardinger enzyme; xanthine oxidoreductase; hypoxanthine-xanthine oxidase; xanthine:O₂ oxidoreductase; xanthine:xanthine oxidase

Systematic name: xanthine:oxygen oxidoreductase

Comments: An iron-molybdenum flavoprotein (FAD) containing [2Fe-2S] centres. Also oxidizes hypoxanthine, some other purines and pterins, and aldehydes, but is distinct from EC 1.2.3.1, aldehyde oxidase. Under some conditions the product is mainly superoxide rather than peroxide: RH + H₂O + 2 O₂ = ROH + 2 O₂^.- + 2 H⁺. The mammalian enzyme predominantly exists as an NAD-dependent dehydrogenase (EC 1.17.1.4, xanthine dehydrogenase). During purification the enzyme is largely converted to the O₂-dependent xanthine oxidase form (EC 1.17.3.2). The conversion can be triggered by several mechanisms, including the oxidation of cysteine thiols to form disulfide bonds [4,5,7,10] [which can be catalysed by EC 1.8.4.7, enzyme-thiol transhydrogenase (glutathione-disulfide) in the presence of glutathione disulfide] or limited proteolysis, which results in irreversible conversion. The conversion can also occur in vivo [4,6,10].

Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9002-17-9

References:

1. Avis, P.G., Bergel, F. and Bray, R.C. Cellular constituents. The chemistry of xanthine oxidase. Part I. The preparation of a crystalline xanthine oxidase from cow's milk. J. Chem. Soc. (Lond.) (1955) 1100-1105.

2. Battelli, M.G. and Lorenzoni, E. Purification and properties of a new glutathione-dependent thiol:disulphide oxidoreductase from rat liver. Biochem. J. 207 (1982) 133-138. [PMID: 6960894]

3. Bray, R.C. Xanthine oxidase. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Eds), The Enzymes, 2nd edn, vol. 7, Academic Press, New York, 1963, pp. 533-556.

4. Della Corte, E. and Stirpe, F. The regulation of rat liver xanthine oxidase. Involvement of thiol groups in the conversion of the enzyme activity from dehydrogenase (type D) into oxidase (type O) and purification of the enzyme. Biochem. J. 126 (1972) 739-745. [PMID: 4342395]

5. Ikegami, T. and Nishino, T. The presence of desulfo xanthine dehydrogenase in purified and crude enzyme preparations from rat liver. Arch. Biochem. Biophys. 247 (1986) 254-260. [PMID: 3459393]

6. Engerson, T.D., McKelvey, T.G., Rhyne, D.B., Boggio, E.B., Snyder, S.J. and Jones, H.P. Conversion of xanthine dehydrogenase to oxidase in ischemic rat tissues. J. Clin. Invest. 79 (1987) 1564-1570. [PMID: 3294898]

7. Saito, T., Nishino, T. and Tsushima, K. Interconversion between NAD-dependent and O₂-dependent types of rat liver xanthine dehydrogenase and difference in kinetic and redox properties between them. Adv. Exp. Med. Biol. 253B (1989) 179-183. [PMID: 2610112]

8. Carpani, G., Racchi, M., Ghezzi, P., Terao, M. and Garattini, E. Purification and characterization of mouse liver xanthine oxidase. Arch. Biochem. Biophys. 279 (1990) 237-241. [PMID: 2350174]

9. Eger, B.T., Okamoto, K., Enroth, C., Sato, M., Nishino, T., Pai, E.F. and Nishino, T. Purification, crystallization and preliminary X-ray diffraction studies of xanthine dehydrogenase and xanthine oxidase isolated from bovine milk. Acta Crystallogr. D Biol. Crystallogr. 56 (2000) 1656-1658. [PMID: 11092937]

10. Nishino, T., Okamoto, K., Eger, B.T., Pai, E.F. and Nishino, T. Mammalian xanthine oxidoreductase - mechanism of transition from xanthine dehydrogenase to xanthine oxidase. FEBS J. 275 (2008) 3278-3289. [PMID: 18513323]