title: Exocyclic-keto reductase activities for progesterone and S-warfarin in hepatic microsomes from adult male rats.
abstract: 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.
authors.affiliation: Department of Chemistry, Kent State University, Ohio 44242.
authors.forename: D
authors.initials: D
authors.lastname: Apanovitch
authors.forename: S
authors.initials: S
authors.lastname: Kitareewan
authors.forename: F G
authors.initials: FG
authors.lastname: Walz
mesh_terms: 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*
chemical_list: 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