Human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase is a single-domain multifunctional enzyme -: Characterization of a novel 17β-hydroxysteroid dehydrogenase
Human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase is a single-domain multifunctional enzyme -: Characterization of a novel 17β-hydroxysteroid dehydrogenase
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DOI：
10.1074/jbc.274.21.15014
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发表时间：
1999-05-21
影响因子：
4.8
通讯作者：
Yang, SY
中科院分区：
文献类型：
--
作者：
He, XY;Merz, G;Yang, SY
人脑短链L-3-羟酰辅酶A脱氢酶（SCHAD）被发现催化17 β-雌二醇和二氢雄酮以及醇类的氧化。线粒体已被证明是这种NAD（+）依赖性脱氢酶在细胞中的适当位置，尽管其一级结构与据报道与内质网（ERAB）相关的淀粉样β肽结合蛋白相同。这种脂肪酸β-氧化酶被鉴定为一种新的17 β-羟基类固醇脱氢酶，负责性类固醇激素的失活。纯化的酶的催化速率常数估计为0.66分钟（-1），对17 β-雌二醇和NAD（+）的表观Km值分别为43和50 μ M。该酶对17 β-雌二醇氧化的催化效率与过氧化物酶体17 β-羟基类固醇脱氢酶4型的催化效率相当。因此，人SCHAD基因产物，一种单结构域多功能酶，似乎在两种不同的脂质代谢途径中起作用。由于人脑短链L-3-羟酰辅酶A脱氢酶的催化功能可削弱雌激素的保护作用并在神经元中产生醛类，因此提出脑中高浓度的该酶是阿尔茨海默病的潜在危险因素。
Human brain short chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) was found to catalyze the oxidation of 17 beta-estradiol and dihydroandrosterone as well as alcohols. Mitochondria have been demonstrated to be the proper location of this NAD(+)-dependent dehydrogenase in cells, although its primary structure is identical to an amyloid beta-peptide binding protein reportedly associated with the endoplasmic reticulum (ERAB). This fatty acid beta-oxidation enzyme was identified as a novel 17 beta-hydroxysteroid dehydrogenase responsible for the inactivation of sex steroid hormones. The catalytic rate constant of the purified enzyme was estimated to be 0.66 min(-1) with apparent K-m values of 43 and 50 mu M for 17 beta-estradiol and NAD(+), respectively. The catalytic efficiency of this enzyme for the oxidation of 17 beta-estradiol was comparable with that of peroxisomal 17 beta-hydroxysteroid dehydrogenase type 4, As a result, the human SCHAD gene product, a single-domain multifunctional enzyme, appears to function in two different pathways of lipid metabolism. Because the catalytic functions of human brain short chain L-3-hydroxyacyl-CoA dehydrogenase could weaken the protective effects of estrogen and generate aldehydes in neurons, it is proposed that a high concentration of this enzyme in brain is a potential risk factor for Alzheimer's disease.