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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Autores principales:	Mai Sekine, Ken Okamoto, Kimiyoshi Ichida
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	xanthine oxidoreductase (XOR) xanthine dehydrogenase (XDH) xanthine oxidase (XO) xanthinuria Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d586605759dc4e769e6e572f0fc34d03
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spelling	oai:doaj.org-article:d586605759dc4e769e6e572f0fc34d032021-11-25T16:51:31ZAssociation of Mutations Identified in Xanthinuria with the Function and Inhibition Mechanism of Xanthine Oxidoreductase10.3390/biomedicines91117232227-9059https://doaj.org/article/d586605759dc4e769e6e572f0fc34d032021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1723https://doaj.org/toc/2227-9059Xanthine 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.Mai SekineKen OkamotoKimiyoshi IchidaMDPI AGarticlexanthine oxidoreductase (XOR)xanthine dehydrogenase (XDH)xanthine oxidase (XO)xanthinuriaBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1723, p 1723 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	xanthine oxidoreductase (XOR) xanthine dehydrogenase (XDH) xanthine oxidase (XO) xanthinuria Biology (General) QH301-705.5
spellingShingle	xanthine oxidoreductase (XOR) xanthine dehydrogenase (XDH) xanthine oxidase (XO) xanthinuria Biology (General) QH301-705.5 Mai Sekine Ken Okamoto Kimiyoshi Ichida Association of Mutations Identified in Xanthinuria with the Function and Inhibition Mechanism of Xanthine Oxidoreductase
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.
format	article
author	Mai Sekine Ken Okamoto Kimiyoshi Ichida
author_facet	Mai Sekine Ken Okamoto Kimiyoshi Ichida
author_sort	Mai Sekine
title	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_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_sort	association of mutations identified in xanthinuria with the function and inhibition mechanism of xanthine oxidoreductase
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d586605759dc4e769e6e572f0fc34d03
work_keys_str_mv	AT maisekine associationofmutationsidentifiedinxanthinuriawiththefunctionandinhibitionmechanismofxanthineoxidoreductase AT kenokamoto associationofmutationsidentifiedinxanthinuriawiththefunctionandinhibitionmechanismofxanthineoxidoreductase AT kimiyoshiichida associationofmutationsidentifiedinxanthinuriawiththefunctionandinhibitionmechanismofxanthineoxidoreductase
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Association of Mutations Identified in Xanthinuria with the Function and Inhibition Mechanism of Xanthine Oxidoreductase

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