Mutations in xanthine dehydrogenase gene in subjects with hereditary xanthinuria.

Abstract

Xanthine dehydrogenase is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and uric acid from xanthine during the final stage of purine metabolism. Xanthine dehydrogenase exists as a dimer and each subunit has a molecular weight of 145000. Human xanthine dehydrogenase cDNA consists of 4002 nucleotides (1) and the gene is mapped to chromosome 2p23 (2). Mapping of the functions on xanthine dehydrogenase was performed for 3 peptide domains generated by the protein cleavage (1). The N-terminal 20 kD domain includes a 2Fe/2S non-heme iron binding site while the adjacent 40 kD and the C-terminal 85 kD domains include flavin binding and molybdenum cofactor binding domains, respectively (1). Most of xanthine dehydrogenase usually exist as the dehydrogenase form and the enzyme is converted to the oxidase form, xanthine oxidase, by the proteolytic cleavage and the oxidation of cystein residues under certain conditions (3). Xanthine dehydrogenase has recently been attracting attention for its possible involvement in triggering tissue damage by producing free radicals. It is exhibited in many studies that xanthine oxidase injured the tissues on the conditions, such as post-ischemic reperfusion tissue injury, adult respiratory distress syndrome and lung injury resulting from influenza virus infection (4–8).KeywordsXanthine OxidaseAdult Respiratory Distress SyndromeInfluenza Virus InfectionDuodenal MucosaAldehyde OxidaseThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.