3(20)alpha-hydroxysteroid dehydrogenase activity of monkey liver indanol dehydrogenase.
Homogeneous indanol dehydrogenase from monkey liver catalyzed the reversible conversion of 3 alpha- or 20 alpha-hydroxy groups of several bile acids and 5 beta-pregnanes to the corresponding 3- or 20-ketosteroids. The kcat values for the steroids determined at pH 7.4 were low, but the kcat/Km values for the 3-ketosteroids were comparable to or exceeded those for 1-indanol and xenobiotic carbonyl substrates. The enzyme transferred the 4-pro-R-hydrogen atom of NADPH to the 3 beta- or 20 beta-face of the ketosteroid substrate. Competitive inhibition of the hydroxysteroid dehydrogenase activity of the enzyme by medroxyprogesterone acetate, hexestrol, and 1,10-phenanthroline suggests that both 1-indanol and hydroxysteroid are oxidized at the same active site on the enzyme. The specific inhibitor of the enzyme, 1,10-phenanthroline, suppressed the 3 alpha-hydroxysteroid dehydrogenase activity in the crude extract of monkey liver by 50%. The results strongly suggest that indanol dehydrogenase acts as a 3(20)alpha-hydroxysteroid dehydrogenase in the metabolism of certain steroid hormones and bile acids.
Hara
A
A
Department of Biochemistry, Gifu Pharmaceutical University.
Nakagawa
M
M
Taniguchi
H
H
Sawada
H
H
D015089:20-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D006589:Hexestrol / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D008251:Macaca; D008297:Male; D008525:Medroxyprogesterone / Q000031:analogs & derivatives / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D010618:Phenanthrolines / Q000494:pharmacology; D013379:Substrate Specificity
D001647:Bile Acids and Salts; D010618:Phenanthrolines; D006589:Hexestrol; D017258:Medroxyprogesterone Acetate; D015096:3-Hydroxysteroid Dehydrogenases; D000429:Alcohol Oxidoreductases; D015089:20-Hydroxysteroid Dehydrogenases; C046532:indanol dehydrogenase; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D008525:Medroxyprogesterone; C025205:1,10-phenanthroline