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人胎盘5-烯-3β-羟类固醇氧化还原酶的类固醇特异性

Steroid specificity of human placental 5-ene-3 beta-hydroxysteroid oxidoreductase.

作者信息

Yoshida N

出版信息

Steroids. 1979 Jan;33(1):9-21. doi: 10.1016/s0039-128x(79)80002-1.

DOI:10.1016/s0039-128x(79)80002-1
PMID:36690
Abstract

The properties of 5-ene-3 beta hydroxysteroid oxidoreductase (3 beta-HSD) from human placental homogenates were studied in vitro. The apparent Michaelis constants for 3 beta-HSD with the substrates pregnenolone (delta 5P) and dehydroepiandrosterone (DHA) were 170 nM and nM respectively. The optimal pH for both these substrates was between 10 and 12. With NAD as the substrate, the Km for the pregnenolone was 20 microM and for DHA, 17 microM. The activity of 3 beta-HSD was inhibited by various steroids. Competitive inhibitors (pregnenolone substrate) included: ethynylestradiol (inhibition constant Ki=7.3 nM), DHA (Ki=46 nM), estradiol-17 beta (Ki=46 nM), cholesterol (Ki=0.68 microM) and 16 alpha-hydroxydehydroepiandrosterone (16 alphaOHDHA) (Ki=2.2 microM). When the substrate was DHA, competitive inhibition occurred with the following steroids: ethynylestradiol (Ki=6.4 nM), estradiol-17 beta (Ki=69 nM), pregnenolone (Ki=91 nM), cholesterol (Ki=1.3 microM) and 16 alphaOHDHA (Ki=1.9 microM). 4-Ene-3-ketosteroids such as androstenedione, progesterone (delta 4P), norethindrone and chlormadinone acetate acted as noncompetitive inhibitors towards both substrates.

摘要

对人胎盘匀浆中的5-烯-3β-羟基类固醇氧化还原酶(3β-HSD)的特性进行了体外研究。3β-HSD对孕烯醇酮(δ5P)和脱氢表雄酮(DHA)这两种底物的表观米氏常数分别为170 nM和 nM。这两种底物的最适pH值在10至12之间。以NAD作为底物时,孕烯醇酮的Km为20 μM,DHA的Km为17 μM。3β-HSD的活性受到多种类固醇的抑制。竞争性抑制剂(孕烯醇酮底物)包括:乙炔雌二醇(抑制常数Ki = 7.3 nM)、DHA(Ki = 46 nM)、雌二醇-17β(Ki = 46 nM)、胆固醇(Ki = 0.68 μM)和16α-羟基脱氢表雄酮(16αOHDHA)(Ki = 2.2 μM)。当底物为DHA时,以下类固醇会产生竞争性抑制作用:乙炔雌二醇(Ki = 6.4 nM)、雌二醇-17β(Ki = 69 nM)、孕烯醇酮(Ki = 91 nM)、胆固醇(Ki = 1.3 μM)和16αOHDHA(Ki = 1.9 μM)。4-烯-3-酮类固醇,如雄烯二酮、孕酮(δ4P)、炔诺酮和醋酸氯地孕酮,对这两种底物均起非竞争性抑制剂的作用。

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