Exocyclic-keto reductase activities for progesterone and S-warfarin in hepatic microsomes from adult male rats.
Hepatic microsomes from adult male rats representing six inbred strains catalyzed quantitatively significant, NADPH dependent reductions of progesterone to the 20 beta (20R) alcohol and S-warfarin to its 11S-OH product. Microsomes from mature females and immature rats of both sexes were essentially devoid of these activities. Two strains of rat evidenced about 21% of these activities compared with the other strains and both activities were 25-81% repressed by treatment of rats with phenobarbital (PB). An excellent linear correlation was demonstrated for the two activities considering sex, age, NADPH much greater than NADH preference, PB-repression and strain differences. However, detergent latency (71%) and resistance to trypsinolysis were only observed for the keto-reductase activity with S-warfarin. Microsomes also catalyzed the reduction of progesterone to its 20 alpha-OH derivative but this activity preferred NADH greater than NADPH, was induced 2.7-fold by PB and was essentially independent of age, sex and animal strain. Furthermore, unlike the 20 beta-OH activity, this reduction was resistant to proteolytic inactivation.
Apanovitch
D
D
Department of Chemistry, Kent State University, Ohio 44242.
Kitareewan
S
S
Walz
F G
FG
D015089:20-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D013045:Species Specificity; D014859:Warfarin / Q000378:metabolism*
D009243:NAD; D011374:Progesterone; D009249:NADP; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; D000429:Alcohol Oxidoreductases; D015089:20-Hydroxysteroid Dehydrogenases; C074128:S-warfarin keto reductase; C074127:progesterone 20-keto-reductase; D010634:Phenobarbital