Introduction and Overview of the Aldo-Keto Reductase Superfamily
Introduction and Overview of the Aldo-Keto Reductase Superfamily
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DOI：
10.1021/bk-2003-0865.ch001
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发表时间：
2003-10
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影响因子：
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通讯作者：
T. Penning
中科院分区：
文献类型：
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作者：
T. Penning
醛酮还原酶（AKR）是一个快速增长的基因超家族，参与高渗糖的形成，这可能有助于糖尿病并发症。它们还代谢活性醛类、甘草素、类固醇激素、化学致癌物和药物。这些酶（>115）通常是单体的、胞质的、NAD（P）H依赖性氧化还原酶，其具有高序列同一性（<40%）和相似的三维结构，例如，（α/β）8桶形，分属14科。有关14个家庭的完整列表，请访问：www.med.upenn.edu/akr。AKR使内源性毒物解毒，例如，衍生自脂质氢过氧化物分解的细胞毒性/致突变双功能亲电体。AKR还代谢外源性有毒物质。它们在烟草致癌中起作用，因为它们催化尼古丁衍生的亚硝胺酮的解毒并活化多环芳香族反式二氢二醇以产生反应性和氧化还原活性的邻醌。离散的同工酶也能使真菌毒素代谢物解毒，例如，黄曲霉毒素二醛和防止肝细胞癌。黄曲霉毒素还原酶由癌症化学预防剂诱导，乙氧喹越来越多的证据表明，AKR是应激调控基因，在细胞对渗透压、亲电和氧化应激的反应中起着重要作用。
Aldo-Keto Reductases (AKRs) are a rapidly growing gene superfamily involved in the formation of hyperosmotic sugars, which can contribute to diabetic complications. They also metabolize reactive aldehydes, prostaglandins, steroid hormones, chemical carcinogens and drugs. These enzymes (>115) are generally monomeric, cytosolic, NAD(P)H-dependent-oxidoreductases, that share high sequence identity (<40%) and similar three-dimensional-structures e.g., (α/β)8-barrels and belong to 14 families. For a complete listing of the 14 families visit: www.med.upenn.edu/akr. AKRs detoxify endogenous toxicants, e.g., cytotoxic/mutagenic bifunctional electrophiles derived from the decomposition of lipid hydroperoxides. AKRs also metabolize exogenous toxic substances. They play a role in tobacco-carcinogenesis since they catalyze the detoxication of nicotine derived nitrosamino-ketones and activate polycyclic aromatictrans-dihydrodiols to yield reactive and redox activeortho-quinones. Discrete isozymes also detoxify mycotoxin metabolites, e.g., aflatoxin dialdehyde and protect against hepatocellular carcinoma. The aflatoxin reductases are induced by cancer chemopreventive agents, e.g., ethoxyquin. Evidence is mounting that AKRs are stress regulated genes and play a central role in the cellular response to osmotic, electrophilic and oxidative stress.