Rat NAD+-dependent 3alpha-hydroxysteroid dehydrogenase (AKR1C17): a member of the aldo-keto reductase family highly expressed in kidney cytosol.
Rat NAD+-dependent 3alpha-hydroxysteroid dehydrogenase (AKR1C17): a member of the aldo-keto reductase family highly expressed in kidney cytosol.
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大鼠 NAD 依赖性 3α-羟基类固醇脱氢酶 (AKR1C17)：醛酮还原酶家族的成员，在肾细胞质中高度表达。
DOI：
10.1016/j.abb.2007.04.003
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发表时间：
2007
影响因子：
3.9
通讯作者：
A. Harã
中科院分区：
文献类型：
--
作者：
Masaharu Sanai;S. Endo;T. Matsunaga;S. Ishikura;K. Tajima;O. El;A. Harã
哺乳动物3α-羟基类固醇脱氢酶（3α-HSDs）分为两类：醛酮还原酶家族的胞浆NADP（H）依赖性3α-HSDs和短链脱氢酶/还原酶家族的线粒体和微粒体NAD+依赖性3α-HSDs。在这项研究中，我们的特点是大鼠醛酮还原酶（AKR 1C 17），其功能是未知的。重组AKR 1C 17在pH7.4 -9.5范围内以NAD+为辅酶，能有效地氧化3α-羟基类固醇和胆汁酸，并能被氯胺酮和有机阴离子抑制。在大鼠肾脏中特异性检测到AKR 1C 17的mRNA，其中该酶作为胞浆蛋白的表达高于NADP（H）依赖性3α-HSD（AKR 1C 9）。因此，AKR 1C 17代表了一种新的NAD+依赖型细胞溶质3α-HSD，具有独特的抑制剂敏感性和组织分布。此外，AKR 1C 17的Gln 270和Glu 276被NADP（H）依赖性3α-HSD的相应残基取代导致有利于NADP+特异性的转换，表明它们在辅酶特异性中的关键作用。
Mammalian 3α-hydroxysteroid dehydrogenases (3α-HSDs) have been divided into two types: Cytosolic NADP(H)-dependent 3α-HSDs belonging to the aldo-keto reductase family, and mitochondrial and microsomal NAD+-dependent 3α-HSDs belonging to the short-chain dehydrogenase/reductase family. In this study, we characterized a rat aldo-keto reductase (AKR1C17), whose functions are unknown. The recombinant AKR1C17 efficiently oxidized 3α-hydroxysteroids and bile acids using NAD+as the preferred coenzyme at an optimal pH of 7.4–9.5, and was inhibited by ketamine and organic anions. The mRNA for AKR1C17 was detected specifically in rat kidney, where the enzyme was more highly expressed as a cytosolic protein than NADP(H)-dependent 3α-HSD (AKR1C9). Thus, AKR1C17 represents a novel NAD+-dependent type of cytosolic 3α-HSD with unique inhibitor sensitivity and tissue distribution. In addition, the replacement of Gln270 and Glu276 of AKR1C17 with the corresponding residues of NADP(H)-dependent 3α-HSD resulted in a switch in favor of NADP+specificity, suggesting their key roles in coenzyme specificity.
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影响因子：
5.8
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DOI：
--
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