HUMAN HEPATIC CORTISOL REDUCTASE ACTIVITIES - ENZYMATIC-PROPERTIES AND SUBSTRATE SPECIFICITIES OF CYTOSOLIC CORTISOL DELTA-4-5-BETA-REDUCTASE AND DIHYDROCORTISOL-3-ALPHA-OXIDOREDUCTASE(S)

被引:22
作者
IYER, RB [1 ]
BINSTOCK, JM [1 ]
SCHWARTZ, IS [1 ]
GORDON, GG [1 ]
WEINSTEIN, BI [1 ]
SOUTHREN, AL [1 ]
机构
[1] NEW YORK MED COLL,DEPT MED,VALHALLA,NY 10595
关键词
STEROIDS; REDUCTASES; HEPATIC REDUCTASES; CORTISOL;
D O I
10.1016/0039-128X(90)90087-R
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
The metabolism of cortisol by human liver homogenates has been studied. Cortisol DELTA-4-reductase and dihydrocortisol-3-oxidoreductase activities were distributed in all subcellular fractions. The products of the soluble enzymes were identified. Cortisol and 5-beta-dihydrocortisol were reduced to 3-alpha,5-beta-tetrahydrocortisol, and 5-alpha-dihydrocortisol was reduced to 3-alpha, 5-alpha-tetrahydrocortisol. The soluble enzymes showed a wide range of substrate specificity. The 21 substituted cortisol derivatives were not metabolized. The apparent Km values of cortisol DELTA-4-5-beta-reductase and dihydrocortisol-3-alpha-oxidoreductase for their substrates (cortisol, 5-alpha-dihydrocortisol, and 5-beta-dihydrocortisol) all ranged from 18 to 27-mu-M. Dexamethasone inhibited the reduction of all of these substrates and the inhibition was abolished by 21 substitution of the dexamethasone. Testosterone was a competitive inhibitor of the reduction of cortisol, 5-alpha-dihydrocortisol, and 5-beta-dihydrocortisol with a K(i) ranging from 11 to 32-mu-M. NADPH was the preferred cofactor for the cortisol DELTA-4-5-beta-reductase and dihydrocortisol-3-alpha-oxidoreductase. No end product inhibition was observed.
引用
收藏
页码:495 / 500
页数:6
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