Oxidation and reduction of bile acid precursors by rat hepatic 3 alpha-hydroxysteroid dehydrogenase and inhibition by bile acids and indomethacin.
Enzyme kinetics of purified rat hepatic 3 alpha-hydroxysteroid dehydrogenase for bile acid precursors and effects of bile acids and indomethacin on those activities were studied. This enzyme catalyzed the oxidoreduction of the C3 position of bile acid precursors. Km for 7 alpha, 12 alpha-dihydroxy-5 beta-cholestan-3-one (1.6 microM) was markedly lower than Km for 7 alpha-hydroxy-5 beta-cholestan-3-one (28 microM) but Vmax was similar. Km for 3 alpha, 7 alpha-dihydroxy-5 beta-cholestane (12 microM) was lower than Km for 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestane (150 microM) although Vmax/Km values were similar for both compounds. Bile acids and indomethacin inhibited the reduction of 3-oxo bile acid precursors. NADPH inhibited the binding of lithocholic acid (3 alpha-hydroxy-5 beta-cholanic acid) by 3 alpha-hydroxysteroid dehydrogenase. These data suggest that intrahepatic bile acid concentrations may affect the reduction of 3-oxo-bile acid precursors and intrahepatic redox conditions may affect intracellular bile acid transfer.
Takikawa
H
H
Liver Research Laboratory, West Los Angeles Veterans Administration Hospital Center Wadsworth Division, CA.
Stolz
A
A
Kuroki
S
S
Kaplowitz
N
N
D015096:3-Hydroxysteroid Dehydrogenases / Q000494:pharmacology*; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002793:Cholic Acids / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology*; D007700:Kinetics; D008095:Lithocholic Acid / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009249:NADP / Q000378:metabolism / Q000502:physiology*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001647:Bile Acids and Salts; D002793:Cholic Acids; D009249:NADP; D008095:Lithocholic Acid; D010088:Oxidoreductases; D015096:3-Hydroxysteroid Dehydrogenases; D007213:Indomethacin