Association of Mutations Identified in Xanthinuria with the Function and Inhibition Mechanism of Xanthine Oxidoreductase
Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the two-step reaction from hypoxanthine to xanthine and from xanthine to uric acid in purine metabolism. XOR generally carries dehydrogenase activity (XDH) but is converted into an oxidase (XO) under various pathophysiologic conditions. The c...
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MDPI AG
2021-11-01
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| Online Access: | https://www.mdpi.com/2227-9059/9/11/1723 |
| _version_ | 1797511104612532224 |
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| author | Mai Sekine Ken Okamoto Kimiyoshi Ichida |
| author_facet | Mai Sekine Ken Okamoto Kimiyoshi Ichida |
| author_sort | Mai Sekine |
| collection | DOAJ |
| description | Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the two-step reaction from hypoxanthine to xanthine and from xanthine to uric acid in purine metabolism. XOR generally carries dehydrogenase activity (XDH) but is converted into an oxidase (XO) under various pathophysiologic conditions. The complex structure and enzymatic function of XOR have been well investigated by mutagenesis studies of mammalian XOR and structural analysis of XOR–inhibitor interactions. Three XOR inhibitors are currently used as hyperuricemia and gout therapeutics but are also expected to have potential effects other than uric acid reduction, such as suppressing XO–generating reactive oxygen species. Isolated XOR deficiency, xanthinuria type I, is a good model of the metabolic effects of XOR inhibitors. It is characterized by hypouricemia, markedly decreased uric acid excretion, and increased serum and urinary xanthine concentrations, with no clinically significant symptoms. The pathogenesis and relationship between mutations and XOR activity in xanthinuria are useful for elucidating the biological role of XOR and the details of the XOR reaction process. In this review, we aim to contribute to the basic science and clinical aspects of XOR by linking the mutations in xanthinuria to structural studies, in order to understand the function and reaction mechanism of XOR in vivo. |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T05:41:40Z |
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| spelling | doaj.art-d586605759dc4e769e6e572f0fc34d032023-11-22T22:32:36ZengMDPI AGBiomedicines2227-90592021-11-01911172310.3390/biomedicines9111723Association of Mutations Identified in Xanthinuria with the Function and Inhibition Mechanism of Xanthine OxidoreductaseMai Sekine0Ken Okamoto1Kimiyoshi Ichida2Department of Pathophysiology, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanDepartment of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, JapanDepartment of Pathophysiology, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanXanthine oxidoreductase (XOR) is an enzyme that catalyzes the two-step reaction from hypoxanthine to xanthine and from xanthine to uric acid in purine metabolism. XOR generally carries dehydrogenase activity (XDH) but is converted into an oxidase (XO) under various pathophysiologic conditions. The complex structure and enzymatic function of XOR have been well investigated by mutagenesis studies of mammalian XOR and structural analysis of XOR–inhibitor interactions. Three XOR inhibitors are currently used as hyperuricemia and gout therapeutics but are also expected to have potential effects other than uric acid reduction, such as suppressing XO–generating reactive oxygen species. Isolated XOR deficiency, xanthinuria type I, is a good model of the metabolic effects of XOR inhibitors. It is characterized by hypouricemia, markedly decreased uric acid excretion, and increased serum and urinary xanthine concentrations, with no clinically significant symptoms. The pathogenesis and relationship between mutations and XOR activity in xanthinuria are useful for elucidating the biological role of XOR and the details of the XOR reaction process. In this review, we aim to contribute to the basic science and clinical aspects of XOR by linking the mutations in xanthinuria to structural studies, in order to understand the function and reaction mechanism of XOR in vivo.https://www.mdpi.com/2227-9059/9/11/1723xanthine oxidoreductase (XOR)xanthine dehydrogenase (XDH)xanthine oxidase (XO)xanthinuria |
| spellingShingle | Mai Sekine Ken Okamoto Kimiyoshi Ichida Association of Mutations Identified in Xanthinuria with the Function and Inhibition Mechanism of Xanthine Oxidoreductase Biomedicines xanthine oxidoreductase (XOR) xanthine dehydrogenase (XDH) xanthine oxidase (XO) xanthinuria |
| title | Association of Mutations Identified in Xanthinuria with the Function and Inhibition Mechanism of Xanthine Oxidoreductase |
| title_full | Association of Mutations Identified in Xanthinuria with the Function and Inhibition Mechanism of Xanthine Oxidoreductase |
| title_fullStr | Association of Mutations Identified in Xanthinuria with the Function and Inhibition Mechanism of Xanthine Oxidoreductase |
| title_full_unstemmed | Association of Mutations Identified in Xanthinuria with the Function and Inhibition Mechanism of Xanthine Oxidoreductase |
| title_short | Association of Mutations Identified in Xanthinuria with the Function and Inhibition Mechanism of Xanthine Oxidoreductase |
| title_sort | association of mutations identified in xanthinuria with the function and inhibition mechanism of xanthine oxidoreductase |
| topic | xanthine oxidoreductase (XOR) xanthine dehydrogenase (XDH) xanthine oxidase (XO) xanthinuria |
| url | https://www.mdpi.com/2227-9059/9/11/1723 |
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