Mutations associated with functional disorder of xanthine oxidoreductase and hereditary xanthinuria in humans.
Mutations associated with functional disorder of xanthine oxidoreductase and hereditary xanthinuria in humans.
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DOI：
10.3390/ijms131115475
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发表时间：
2012-11-21
影响因子：
5.6
通讯作者：
Nishino T
中科院分区：
文献类型：
--
作者：
Ichida K;Amaya Y;Okamoto K;Nishino T
黄嘌呤氧化还原酶（XOR）催化次黄嘌呤转化为黄嘌呤和黄嘌呤转化为尿酸，同时伴有NAD+或O2的还原。这种酶是治疗高尿酸血症、痛风和活性氧相关疾病的药物的靶点。与遗传决定的XOR功能障碍相关的人类疾病被称为黄嘌呤尿症，因为黄嘌呤在尿液中排泄。黄嘌呤尿分为两种亚型，I型和II型。I型黄嘌呤尿症涉及由于XOR的遗传缺陷而导致的XOR缺陷，而II型黄嘌呤尿症涉及由于钼辅因子硫酸化酶的遗传缺陷而导致的XOR和醛氧化酶（AO，一种类似于XOR的黄酮酶）的双重缺陷。钼辅因子缺乏症与XOR、AO和亚硫酸盐氧化酶的三重缺乏症相关，这是由于作为所有三种酶的钼辅因子的前体的白蝶呤的合成缺陷所致。本文综述了哺乳动物XOR的突变或化学修饰研究，以及在人类中发现的XOR突变，旨在了解XOR的反应机制和突变XOR作为模型的相关性，以估计临床应用XOR抑制剂可能产生的副作用。
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.
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影响因子：
2
作者：
Al-Eisa, A. A.;Al-Hunayyan, A.;Gupta, R.
通讯作者：
Gupta, R.
DOI：
10.1073/pnas.78.11.6858
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
AMES, BN;CATHCART, R;HOCHSTEIN, P
通讯作者：
HOCHSTEIN, P
影响因子：
56.9
作者：
ELION, GB
通讯作者：
ELION, GB
影响因子：
3
作者：
Arikyants, Nina;Sarkissian, Ashot;Steinmann, Beat
通讯作者：
Steinmann, Beat
影响因子：
168.9
作者：
DENT, CE;PHILPOT, GR
通讯作者：
PHILPOT, GR