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Mammalian xanthine oxidoreductase – mechanism of transition from xanthine dehydrogenase to xanthine oxidase
Author(s) -
Nishino Tomoko,
Okamoto Ken,
Eger Bryan T.,
Pai Emil F.,
Nishino Takeshi
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06489.x
Subject(s) - xanthine dehydrogenase , xanthine oxidase , superoxide , oxidoreductase , chemistry , biochemistry , reactive oxygen species , enzyme , hydrogen peroxide , xanthine , dehydrogenase
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.