人肝脏中与NADPH相关的醛还原酶的动力学研究。

Kinetic studies on NADPH-linked aldehyde reductase from human liver.

作者信息

Wermuth B, von Wartburg J P

出版信息

Adv Exp Med Biol. 1980;132:189-95. doi: 10.1007/978-1-4757-1419-7_20.

Abstract

The mechanism of D-glucuronate reduction by human liver NADPH-dependent aldehyde reductase was investigated. At pH 7.4 the Km values for NADPH, NADP+, D-glucuronate and L-gulonate were 2.2 microM, 6 microM, 3.2 mM and 6 mM, respectively. Product inhibition studies in the forward direction (reduction of glucuronate) gave a competitive pattern for the inhibition of NADPH oxidation by NADP+ and non-competitive patterns for the other three inhibitions. In the backward direction all patterns appeared to be competitive. Deuterium isotope effects were dependent on the concentration of D-glucuronate and decreased to unity at infinite concentrations of D-glucuronate. Our findings suggest for aldehyde reductase a kinetic mechanism with sequential ordered binding of NADPH and D-glucuronate and random dissociation of NADP+ and L-gulonate.

摘要

对人肝脏NADPH依赖性醛还原酶还原D-葡萄糖醛酸的机制进行了研究。在pH 7.4时，NADPH、NADP⁺、D-葡萄糖醛酸和L-古洛糖酸的Km值分别为2.2微摩尔、6微摩尔、3.2毫摩尔和6毫摩尔。正向（葡萄糖醛酸还原）的产物抑制研究显示，NADP⁺对NADPH氧化的抑制呈竞争性模式，而其他三种抑制呈非竞争性模式。在反向反应中，所有模式似乎都是竞争性的。氘同位素效应取决于D-葡萄糖醛酸的浓度，并在D-葡萄糖醛酸无限浓度时降至1。我们的研究结果表明，醛还原酶的动力学机制是NADPH和D-葡萄糖醛酸依次有序结合，NADP⁺和L-古洛糖酸随机解离。