IDENTIFICATION OF LANOSTEROL 14-ALPHA-METHYL DEMETHYLASE IN HUMAN TISSUES

被引：11

作者：

RAUCY, JL ^{[1
]}

CARPENTER, SJ ^{[1
]}

TRZASKOS, JM ^{[1
]}

机构：

[1] DUPONT MERCK PHARMACEUT CO,WILMINGTON,DE 19880

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1991年 / 177卷 / 01期

关键词：

D O I：

10.1016/0006-291X(91)92011-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Lanosterol 14α-methyl demethylase was investigated in human tissues using a radio-HPLC assay to detect the 4,4-dimethyl-5α-cholesta-8,14-dien-3β-ol (diene) metabolite. The sequence of events leading to the demethylated product in human liver microsomes involves the conversion of the diol to the aldehyde followed by diene formation. Enzyme activity displayed a greater than 10 fold variation among the 9 liver samples studied. Kinetic parameters were determined and shown to differ between two separate liver samples. Addition of inhibitors of yeast lanosterol 14α demethylase, ketoconazole and miconazole, resulted in extensive inhibition of formation of the demethylated metabolite. The enzyme, detected in microsomes isolated from human kidney and lymphocytes, also catalyzed the conversion of dihydrolanosterol to oxylanosterol intermediates and the diene. The presence of this enzyme in microsomes from various human tissues suggests that it may play a role in cellular regulation of cholesterol synthesis. © 1991.

引用

页码：497 / 503

页数：7

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