title: Kinetic studies on rat liver 11 beta-hydroxysteroid dehydrogenase.
abstract: The kinetic behavior of homogeneous rat liver 11 beta-hydroxysteroid dehydrogenase (11-HSD) was investigated. The purified enzyme catalyzed oxidation of the 11 beta-hydroxy steroids, cortisol and corticosterone, to their 11-oxo products. The reverse 11-oxoreductase was not detected. Initial velocity studies of 11 beta-dehydrogenase were consistent with a sequential bireactant mechanism. Glycyrrhetinic acid, a competitive inhibitor of corticosterone oxidation, was uncompetitive with respect to NADP+. The observed inhibition patterns were consistent with an ordered sequential mechanism with NADP+ adding to the enzyme first. Analogs of NADP+ and NAD+ did not inhibit steroid oxidation by 11-HSD, nor did the products of the 11 beta-dehydrogenase reaction slow oxidation, or catalyze reduction. Ligand binding studies generated patterns that supported the ordered sequential mechanism derived from kinetic studies. The kinetic behavior of 11-HSD is therefore similar to other alcohol dehydrogenases. The basis for the apparent inability of homogeneous 11-HSD to catalyze reduction remains to be established.
authors.affiliation: Population Council, New York 10021.
authors.forename: C
authors.initials: C
authors.lastname: Monder
authors.forename: V
authors.initials: V
authors.lastname: Lakshmi
authors.forename: Y
authors.initials: Y
authors.lastname: Miroff
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D001667:Binding, Competitive; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D009243:NAD / Q000031:analogs & derivatives / Q000494:pharmacology; D009249:NADP / Q000031:analogs & derivatives / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats
chemical_list: D009243:NAD; D009249:NADP; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006034:Glycyrrhetinic Acid