摘要
The metabolism of steroids and retinoids has been studied in detail for a long time, as these compounds are involved in a broad spectrum of physiological processes. Many enzymes participating in the conversion of such compounds are members of the short-chain dehydrogenase/reductase (SDR) superfamily. Despite great effort, there still remain a number of poorly characterized SDR proteins. According to various bioinformatics predictions, many of these proteins may play a role in the metabolism of steroids and retinoids. Dehydrogenase/reductase (SDR family) member 7 (DHRS7) is one such protein. In a previous study, we determined DHRS7 to be an integral membrane protein of the endoplasmic reticulum facing the lumen which has shown at least in vitro NADPH-dependent reducing activity toward several eobiotics and xenobiotics bearing a carbonyl moiety. In the present paper pure DHRS7 was used for a more detailed study of both substrate screening and an analysis of kinetics parameters of the physiologically important substrates androstene-3,17-dione, cortisone and all-trans-retinal. Expression patterns of DHRS7 at the mRNA as well as protein level were determined in a panel of various human tissue samples, a procedure that has enabled the first estimation of the possible biological function of this enzyme. DHRS7 is expressed in tissues such as prostate, adrenal glands, liver or intestine, where its activity could be well exploited. Preliminary indications show that DHRS7 exhibits dual substrate specificity recognizing not only steroids but also retinoids as potential substrates and could be important in the metabolism of these signalling molecules.
摘要译文
类固醇和类视黄醇的代谢已详细研究了很长的时间，因为这些化合物参与生理过程的广谱参与这种化合物的转化多种酶是短链脱氢酶/还原酶（SDR）的成员superfamilyDespite很大的努力，仍然存在许多其特征很差SDR proteinsAccording的各种生物信息学预测，许多这些蛋白质可以以类固醇和类视黄酸的代谢中发挥作用脱氢酶/还原酶（SDR家族）成员7（DHRS7）就是这样的一个proteinIn先前的研究中，面对管腔内质网的人膜蛋白，其已经显示出至少在体外NADPH依赖性减少朝向几个eobiotics和异生素的轴承羰基部分的活性在本纸张纯DHRS7用于两个基板筛选的更详细的研究，并在生理上的重要底物雄甾烯-3,17-二酮的动力学参数的分析，在mRNA以及蛋白水平DHRS7可的松和全反式retinalExpression型态在各种人组织样品的一个面板进行测定，已启用该enzymeDHRS7的可能的生物功能的第一估计的过程在组织如前列腺，肾上腺，肝脏或肠表达，其中，它的活动能很好地利用离子显示DHRS7表现出双重底物特异性识别不仅类固醇而且类视色素的潜在底物，可以是在这些信号分子的代谢重要
Hana Štambergová[a]; Lucie Zemanová[a]; Tereza Lundová[a]; Beata Malčeková[a]; Adam Skarka[a]; Miroslav Šafr[b]; Vladimír Wsól[a]. Human DHRS7, promising enzyme in metabolism of steroids and retinoids?[J]. The Journal of Steroid Biochemistry and Molecular Biology, 2016,155(PartA): 112–119