title: Evidence for kinetically distinct forms of corticosteroid 11 beta-dehydrogenase in rat liver microsomes.
abstract: In this paper we have characterized the 11 beta-dehydrogenase component of the 11 beta-hydroxysteroid dehydrogenase complex in rat liver microsomes. This enzyme oxidized cortisol and corticosterone to cortisone and 11-dehydrocorticosterone, respectively. Corticosterone was oxidized 10-20 times faster than cortisol to its 11-oxo product. In freshly isolated microsomes enzyme activity was partially suppressed. Exposure of the microsomes to detergent or to prolonged incubation (24 h) released latent enzyme activity. Latency release was dependent on steroid concentration. The pH-activity profiles of latent and stimulated enzymes differed in shape (concave vs convex) and in pH optimum (pH 10 vs pH 8.5-9.5). Magnitude of latency release was greatest at pH 7. Corticosterone was a potent inhibitor of cortisol oxidation, but cortisol inhibited corticosterone oxidation poorly. With cortisol or corticosterone as substrates, low and high Km species were found. The high Km form represented about 90% of total enzyme activity in untreated microsomes. When latency was released, the low Km form was not detected. Our results suggest that at least two isozymic forms of corticosterone 11 beta-dehydrogenase reside in rat liver microsomes, or that a single enzyme coexists in two kinetically distinguishable forms.
authors.affiliation: Population Council, NY 10021.
authors.forename: C
authors.initials: C
authors.lastname: Monder
authors.forename: V
authors.initials: V
authors.lastname: Lakshmi
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D004795:Enzyme Stability; D006863:Hydrogen-Ion Concentration; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013256:Steroids / Q000494:pharmacology; D013379:Substrate Specificity
chemical_list: D007527:Isoenzymes; D013256:Steroids; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases