Hult M, Jörnvall H, Oppermann U C
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
FEBS Lett. 1998 Dec 11;441(1):25-8. doi: 10.1016/s0014-5793(98)01515-4.
Functional analyses were performed with microsomal human 11beta-hydroxysteroid dehydrogenase type 1 overexpressed in the yeast Pichia pastoris. Cell extracts or microsomes from transformed strains displayed dehydrogenase and reductase activities, which were up to 10 times higher than in human liver microsomes, while for whole cells cortisone reduction but no dehydrogenase activity was observed. The synthetic glucocorticoids prednisolone and prednisone were efficiently metabolized by subcellular fractions, whereas no activity was observed with dexamethasone, budesonide and deflazacort. Inhibitors found to be effective towards the recombinant 11beta-hydroxysteroid dehydrogenase include synthetic steroids and xenobiotic compounds, revealing selective inhibition of the reaction direction, useful for development of specific inhibitors.
利用在毕赤酵母中过表达的人微粒体11β-羟基类固醇脱氢酶1进行功能分析。来自转化菌株的细胞提取物或微粒体表现出脱氢酶和还原酶活性，其活性比人肝微粒体中的活性高10倍，而对于全细胞，观察到可的松还原但未观察到脱氢酶活性。合成糖皮质激素泼尼松龙和泼尼松可被亚细胞组分有效代谢，而地塞米松、布地奈德和去氟可特未观察到活性。发现对重组11β-羟基类固醇脱氢酶有效的抑制剂包括合成类固醇和外源性化合物，揭示了对反应方向的选择性抑制，这对于开发特异性抑制剂很有用。
