Mammalian alcohol dehydrogenase functional and structural implications
Mammalian alcohol dehydrogenase functional and structural implications
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DOI：
10.1159/000054015
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发表时间：
2001-01-01
影响因子：
11
通讯作者：
Svensson, S
中科院分区：
文献类型：
--
作者：
Höög, JO;Hedberg, JJ;Svensson, S
哺乳动物醇脱氢酶（ADH）是一个形式多样、多样性广泛的复杂系统（ADH1-ADH6），可催化多种醇和醛的氧化和还原。ADH1酶，经典的肝脏形式，参与几种代谢途径除了乙醇的氧化，如去甲肾上腺素，多巴胺，血清素和胆汁酸代谢。这类化合物还能进一步将醛氧化成相应的羧酸，即失配。ADH2可分为两个亚组，一组由人酶和兔酶组成，另一组由啮齿动物酶组成。与人类相比，啮齿动物的酶几乎缺乏乙醇氧化能力，这表明啮齿动物是人类乙醇代谢的不良模型系统。ADH3（与谷胱甘肽依赖的甲醛脱氢酶相同）显然是ADH的祖先形式，s -羟甲基谷胱甘肽是主要的生理底物，但该酶仍然可以氧化高浓度的乙醇。ADH4仅在肝外表达，除参与视黄醇代谢外，还可能参与乙醇的首过代谢。更高级别的ADH5和ADH6的研究很少，它们的底物种类也未知。与细胞色素P450系统相比，整个ADH系统可以看作是一个对醇和醛的一般解毒系统，而不会产生有毒自由基。国家科学委员会版权所有ROC和S. Karger公司。巴塞尔协议。
Mammalian alcohol dehydrogenase (ADH) constitutes a complex system with different forms and extensive multiplicity (ADH1-ADH6) that catalyze the oxidation and reduction of a wide variety of alcohols and aldehydes. The ADH1 enzymes, the classical liver forms, are involved in several metabolic pathways beside the oxidation of ethanol, e.g. norepinephrine, dopamine, serotonin and bile acid metabolism. This class is also able to further oxidize aldehydes into the corresponding carboxylic acids, i.e, dismutation. ADH2, can be divided into two subgroups, one group consisting of the human enzyme together with a rabbit form and another consisting of the rodent forms. The rodent enzymes almost lack ethanol-oxidizing capacity in contrast to the human form, indicating that rodents are poor model systems for human ethanol metabolism. ADH3 (identical to glutathione-dependent formaldehyde dehydrogenase) is clearly the ancestral ADH form and S-hydroxymethylglutathione is the main physiological substrate, but the enzyme can still oxidize ethanol at high concentrations. ADH4 is solely extrahepatically expressed and is probably involved in first pass metabolism of ethanol beside its role in retinol metabolism. The higher classes, ADH5 and ADH6, have been poorly investigated and their substrate repertoire is unknown. The entire ADH system can be seen as a general detoxifying system for alcohols and aldehydes without generating toxic radicals in contrast to the cytochrome P450 system. Copyright (C) 2001 National Science Council. ROC and S. Karger AG. Basel.