Int. J. Mol. Sci. 2012, 13(11), 15475-15495; doi:10.3390/ijms131115475
Review

Mutations Associated with Functional Disorder of Xanthine Oxidoreductase and Hereditary Xanthinuria in Humans

1email, 2email, 3email and 3,4,* email
Received: 7 October 2012; in revised form: 26 October 2012 / Accepted: 29 October 2012 / Published: 21 November 2012
(This article belongs to the Special Issue Flavins)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Xanthine oxidoreductase (XOR) catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid with concomitant reduction of either NAD+ or O2. The enzyme is a target of drugs to treat hyperuricemia, gout and reactive oxygen-related diseases. Human diseases associated with genetically determined dysfunction of XOR are termed xanthinuria, because of the excretion of xanthine in urine. Xanthinuria is classified into two subtypes, type I and type II. Type I xanthinuria involves XOR deficiency due to genetic defect of XOR, whereas type II xanthinuria involves dual deficiency of XOR and aldehyde oxidase (AO, a molybdoflavo enzyme similar to XOR) due to genetic defect in the molybdenum cofactor sulfurase. Molybdenum cofactor deficiency is associated with triple deficiency of XOR, AO and sulfite oxidase, due to defective synthesis of molybdopterin, which is a precursor of molybdenum cofactor for all three enzymes. The present review focuses on mutation or chemical modification studies of mammalian XOR, as well as on XOR mutations identified in humans, aimed at understanding the reaction mechanism of XOR and the relevance of mutated XORs as models to estimate the possible side effects of clinical application of XOR inhibitors.
Keywords: xanthine dehydrogenase; xanthine oxidase; xanthine oxidoreductase; xanthine oxidoreductase deficiency; flavoproteins; xanthinuria; hereditary xanthinuria; gout
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MDPI and ACS Style

Ichida, K.; Amaya, Y.; Okamoto, K.; Nishino, T. Mutations Associated with Functional Disorder of Xanthine Oxidoreductase and Hereditary Xanthinuria in Humans. Int. J. Mol. Sci. 2012, 13, 15475-15495.

AMA Style

Ichida K, Amaya Y, Okamoto K, Nishino T. Mutations Associated with Functional Disorder of Xanthine Oxidoreductase and Hereditary Xanthinuria in Humans. International Journal of Molecular Sciences. 2012; 13(11):15475-15495.

Chicago/Turabian Style

Ichida, Kimiyoshi; Amaya, Yoshihiro; Okamoto, Ken; Nishino, Takeshi. 2012. "Mutations Associated with Functional Disorder of Xanthine Oxidoreductase and Hereditary Xanthinuria in Humans." Int. J. Mol. Sci. 13, no. 11: 15475-15495.

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