Jin Yi, Penning Trevor M
Department of Pharmacology, Center of Excellence in Environmental Toxicology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Annu Rev Pharmacol Toxicol. 2007;47:263-92. doi: 10.1146/annurev.pharmtox.47.120505.105337.
Aldo-keto reductases (AKRs) are soluble NAD(P)(H) oxidoreductases that primarily reduce aldehydes and ketones to primary and secondary alcohols, respectively. The ten known human AKR enzymes can turnover a vast range of substrates, including drugs, carcinogens, and reactive aldehydes. They play central roles in the metabolism of these agents, and this can lead to either their bioactivation or detoxication. AKRs are Phase I drug metabolizing enzymes for a variety of carbonyl-containing drugs and are implicated in cancer chemotherapeutic drug resistance. They are involved in tobacco-carcinogenesis because they activate polycyclic aromatic trans-dihydrodiols to yield reactive and redox active o-quinones, but they also catalyze the detoxication of nicotine derived nitrosamino ketones. They also detoxify reactive aldehydes formed from exogenous toxicants, e.g., aflatoxin, endogenous toxicants, and those formed from the breakdown of lipid peroxides. AKRs are stress-regulated genes and play a central role in the cellular response to osmotic, electrophilic, and oxidative stress.
醛酮还原酶（AKRs）是可溶性的NAD(P)(H)氧化还原酶，主要分别将醛和酮还原为伯醇和仲醇。已知的十种人类AKR酶能够作用于大量底物，包括药物、致癌物和活性醛。它们在这些物质的代谢中起核心作用，这可能导致它们的生物活化或解毒。AKRs是多种含羰基药物的I相药物代谢酶，并与癌症化疗耐药性有关。它们参与烟草致癌过程，因为它们能将多环芳烃反式二氢二醇激活，生成具有反应性和氧化还原活性的邻醌，但它们也催化尼古丁衍生的亚硝基氨基酮的解毒。它们还能使由外源性毒物（如黄曲霉毒素）、内源性毒物以及脂质过氧化物分解形成的活性醛解毒。AKRs是应激调节基因，在细胞对渗透压、亲电试剂和氧化应激的反应中起核心作用。
