人肾11β羟类固醇脱氢酶II型酶的克隆

Cloning of the 11 beta HSD type II enzyme from human kidney.

作者信息

Albiston A L, Smith R E, Obeyesekere V R, Krozowski Z S

机构信息

Baker Institute of Medical Research, Melbourne, Australia.

出版信息

Endocr Res. 1995 Feb-May;21(1-2):399-409. doi: 10.3109/07435809509030456.

DOI:10.3109/07435809509030456

PMID:7588404

Abstract

The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) converts glucocorticoids to receptor inactive metabolites. Two isoforms of the enzyme exist. 11 beta HSD1 is a low affinity NADP dependent enzyme, while 11 beta HSD2 is a high affinity NAD dependent species thought to be responsible for endowing specificity on the mineralocorticoid receptor and for protecting the fetus from high circulating levels of maternal glucocorticoids. We have recently cloned the human renal 11 beta HSD2 enzyme. In this report we show that 11 beta HSD2 potently inactivates the synthetic glucocorticoid dexamethasone, producing a single product thought to be the 11-dehydrodexamethasone metabolite. Sequence analysis shows that the new isoform is a member of the short-chain alcohol dehydrogenase superfamily (SCAD), most closely related to 17 beta HSD2 and distantly related to 11 beta HSD1.

摘要

11β-羟基类固醇脱氢酶（11βHSD）可将糖皮质激素转化为受体无活性代谢产物。该酶存在两种同工型。11βHSD1是一种低亲和力的依赖烟酰胺腺嘌呤二核苷酸磷酸（NADP）的酶，而11βHSD2是一种高亲和力的依赖烟酰胺腺嘌呤二核苷酸（NAD）的酶，被认为赋予盐皮质激素受体特异性，并保护胎儿免受母体循环中高浓度糖皮质激素的影响。我们最近克隆了人肾11βHSD2酶。在本报告中，我们表明11βHSD2能有效使合成糖皮质激素地塞米松失活，产生一种单一产物，该产物被认为是11-脱氢地塞米松代谢物。序列分析表明，新的同工型是短链醇脱氢酶超家族（SCAD）的成员，与17βHSD2关系最密切，与11βHSD1关系较远。