He X Y, Merz G, Mehta P, Schulz H, Yang S Y
Departments of Pharmacology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA.
J Biol Chem. 1999 May 21;274(21):15014-9. doi: 10.1074/jbc.274.21.15014.
Human brain short chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) was found to catalyze the oxidation of 17beta-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 17beta-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 Km values of 43 and 50 microM for 17beta-estradiol and NAD+, respectively. The catalytic efficiency of this enzyme for the oxidation of 17beta-estradiol was comparable with that of peroxisomal 17beta-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.
人类脑短链L-3-羟酰基辅酶A脱氢酶（SCHAD）被发现可催化17β-雌二醇、二氢雄甾酮以及醇类的氧化。线粒体已被证明是该NAD⁺依赖性脱氢酶在细胞中的合适定位，尽管其一级结构与据报道与内质网相关的淀粉样β肽结合蛋白（ERAB）相同。这种脂肪酸β氧化酶被鉴定为一种新型的17β-羟类固醇脱氢酶，负责性甾体激素的失活。纯化酶的催化速率常数估计为0.66 min⁻¹，17β-雌二醇和NAD⁺的表观Km值分别为43和50 μM。该酶对17β-雌二醇氧化的催化效率与过氧化物酶体4型17β-羟类固醇脱氢酶相当。因此，人类SCHAD基因产物，一种单结构域多功能酶，似乎在脂质代谢的两条不同途径中发挥作用。由于人类脑短链L-3-羟酰基辅酶A脱氢酶的催化功能可能会削弱雌激素的保护作用并在神经元中产生醛类，因此有人提出脑中该酶的高浓度是阿尔茨海默病的潜在危险因素。
