Polymorphisms of human aldehyde dehydrogenases - Consequences for drug metabolism and disease
Polymorphisms of human aldehyde dehydrogenases - Consequences for drug metabolism and disease
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DOI：
10.1159/000028400
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发表时间：
2000-01-01
期刊：
影响因子：
3.1
通讯作者：
Pappa, A
中科院分区：
文献类型：
--
作者：
Vasiliou, V;Pappa, A
乙醛脱氢酶（ALDH）是一类一级结构相似的NAD（P）（+）依赖性酶超家族，催化多种内源性和外源性脂肪醛和芳香醛的氧化。ALDH 2的多态性与乙醛代谢改变、酒精中毒风险降低和乙醇诱导的癌症风险增加有关。ALDH 3A 2、ALDH 4A 1、ALDH 5A 1和ALDH 6A 1的多态性与通常以神经系统并发症为特征的代谢疾病相关。ALDH 3A 2突变导致酶活性丧失，是Sjogren-Larsson综合征的分子基础。ALDH 4A 1的突变与II型高脯氨酸血症有关，ALDH 5A 1的缺乏导致4-羟丁酸尿症。缺乏ALDH 6A 1似乎与发育迟缓有关。还观察到ALDH 1A 1、ALDH 1B 1、ALDH 3A 1和ALDH 9A 1基因的等位基因变体，但尚未表征。本文综述了ALDH多态性与药物代谢和疾病的关系。版权所有（C）2000 S. Karger AG.巴塞尔。
Aldehyde dehydrogenases (ALDHs), a superfamily of NAD(P)(+)-dependent enzymes with similar primary structures, catalyze the oxidation of a wide spectrum of endogenous and exogenous aliphatic and aromatic aldehydes, Thus far, 16 ALDH genes with distinct chromosomal locations have been identified in the human genome. Polymorphism in ALDH2 is associated with altered acetaldehyde metabolism, decreased risk of alcoholism and increased risk of ethanol-induced cancers. Polymorphisms in ALDH3A2, ALDH4A1, ALDH5A1 and ALDH6A1 are associated with metabolic diseases generally characterized by neurologic complications. Mutations in ALDH3A2 cause loss of enzymatic activity and are the molecular basis of Sjogren-Larsson syndrome. Mutations in ALDH4A1 are associated with type II hyperprolinemia, Deficiency in ALDH5A1 causes 4-hydroxybutyric aciduria. Lack of ALDH6A1 appears to be associated with developmental delay. Allelic variants of the ALDH1A1, ALDH1B1, ALDH3A1 and ALDH9A1 genes have also been observed but not yet characterized. This review describes consequences of ALDH polymorphisms with respect to drug metabolism and disease. Copyright (C) 2000 S. Karger AG. Basel.