Kinetic studies on rat liver 11 beta-hydroxysteroid dehydrogenase.
Kinetic studies on rat liver 11 beta-hydroxysteroid dehydrogenase.
复制标题
大鼠肝脏 11 β-羟基类固醇脱氢酶的动力学研究。
DOI：
10.1016/0304-4165(91)90006-3
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Miroff,Y
中科院分区：
文献类型：
--
作者：
Monder,C;Lakshmi,V;Miroff,Y
研究了均质大鼠肝脏11β-羟基类固醇脱氢酶（11-HSD）的动力学行为。纯化后的酶催化11β-羟基类固醇皮质醇和皮质酮氧化为11-氧产物。未检测到反11-氧还原酶。11β-脱氢酶的初始速度研究符合顺序双反应物机制。甘草次酸是一种竞争性皮质酮氧化抑制剂，对NADP+没有竞争性。观察到的抑制模式符合NADP+首先加入酶的有序顺序机制。NADP+和NAD+的类似物不能抑制类固醇被11-HSD氧化，11β-脱氢酶反应的产物也不能减缓氧化或催化还原。配体结合研究产生的模式支持从动力学研究中得出的有序顺序机制。因此，11-HSD的动力学行为与其他醇脱氢酶相似。均相11-HSD明显不能催化还原的依据仍有待确定。
The kinetic behavior of homogeneous rat liver 11β-hydroxysteroid dehydrogenase (11-HSD) was investigated. The purified enzyme catalyzed oxidation of the 11β-hydroxy steroids, cortisol and corticosterone, to their 11-oxo products. The reverse 11-oxoreductase was not detected. Initial velocity studies of 11β-dehydrogenase were consistent with a sequential bireactant mechanism. Glycyrrhetinic acid, a competitive inhibitor of corticosterone oxidation, was uncompetitive with respect to NADP+. The observed inhibition patterns were consistent with an ordered sequential mechanism with NADP+adding to the enzyme first. Analogs of NADP+and NAD+did not inhibit steroid oxidation by 11-HSD, nor did the products of the 11β-dehydrogenase reaction slow oxidation, or catalyze reduction. Ligand binding studies generated patterns that supported the ordered sequential mechanism derived from kinetic studies. The kinetic behavior of 11-HSD is therefore similar to other alcohol dehydrogenases. The basis for the apparent inability of homogeneous 11-HSD to catalyze reduction remains to be established.