11β-Hydroxysteroid dehydrogenase type 1 from human liver: Dimerization and enzyme cooperativity support its postulated role as glucocorticoid reductase
11β-Hydroxysteroid dehydrogenase type 1 from human liver: Dimerization and enzyme cooperativity support its postulated role as glucocorticoid reductase
复制标题
来自人肝脏的 11β-羟基类固醇脱氢酶 1 型：二聚化和酶协同性支持其作为糖皮质激素还原酶的假设作用
DOI：
10.1021/bi015803t
复制
发表时间：
2002
期刊：
影响因子：
2.9
通讯作者：
J. Friebertshäuser
中科院分区：
文献类型：
--
作者：
Edmund Maser;Bernhard Völker;J. Friebertshäuser
11羟基类固醇脱氢酶1(11β-HSD1)是一种微粒体酶，催化受体活性的11-羟基糖皮质激素(皮质醇)可逆地相互转化为受体非活性的11-氧代谢物(可的松)。然而，由于11β-HSD1的低底物亲和力，在调节糖皮质激素对糖皮质激素受体的通路方面的生理作用仍然不清楚，这与低糖皮质激素血浆水平和受体对皮质醇的低Kd值形成对比。为了解开这个谜团，我们用从人肝脏中纯化的11个β-HSD1进行了详细的动力学分析。通过一种温和的增溶方法以及在各种层析步骤中提供良好的去污剂环境的纯化过程，成功地获得了活性状态的膜结合酶。纯化的11β-HSD1经N-末端、酶活性测定证明具有一定的同源性.
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD 1) is a microsomal enzyme that catalyzes the reversible interconversion of receptor-active 11-hydroxy glucocorticoids (cortisol) to their receptor-inactive 11-oxo metabolites (cortisone). However, the physiological role of 11β-HSD 1 as prereceptor control device in regulating access of glucocorticoid hormones to the glucocorticoid receptor remains obscure in light of its low substrate affinities, which is in contrast to low glucocorticoid plasma levels and low Kd values of the receptors to cortisol. To solve this enigma, we performed detailed kinetic analyses with a homogeneously purified 11β-HSD 1 from human liver. The membrane-bound enzyme was successfully obtained in an active state by a purification procedure that took advantage of a gentle solubilization method as well as providing a favorable detergent surrounding during the various chromatographic steps. The identity of purified 11β-HSD 1 was proven by determination of enzymatic activity, N-terminal ...