MOLECULAR GENETIC-STUDIES ON THE BIOSYNTHESIS OF ALDOSTERONE IN HUMANS

被引:12
作者
SHIZUTA, Y
KAWAMOTO, T
MITSUUCHI, Y
TODA, K
MIYAHARA, K
ICHIKAWA, Y
IMURA, H
ULICK, S
机构
[1] KAGAWA MED SCH,DEPT BIOCHEM,KAGAWA 76107,JAPAN
[2] VET ADM MED CTR,NEW YORK,NY 10468
[3] KYOTO UNIV,FAC MED,DEPT MED,KYOTO 606,JAPAN
关键词
D O I
10.1016/0960-0760(92)90326-E
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
Corticosterone methyl oxidase Type I (CMO I) and II (CMO II) have been postulated to be the enzymes involved in the final two steps of aldosterone biosynthesis in humans. We have isolated human cDNAs for P450c11 and P450c18 as well as the corresponding genes, CYP11B1 and CYP11B2. Both protein products of these two genes as expressed in COS-7 cells exhibit steroid 11beta -hydroxylase activity, but only P450c 1 8, a product of CYP11B2, carried steroid 18-hydroxylase activity to form aldosterone. These results indicate that CYP11B2 encodes CMO, the actual catalytic function of which is retained by P450c18, a multifunctional enzyme. This conclusion is further supported by the finding that the P450c18 gene, CYP11B2, is mutated at several different loci in patients deficient in CMO I or II.
引用
收藏
页码:981 / 987
页数:7
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