Reduction of 7-ketolithocholic acid by human liver enzyme preparations in vitro.
The formation of chenodeoxycholic and ursodeoxycholic acids from 7-ketolithocholic acid by human liver preparations was examined in vitro. Liver preparations were incubated with 7-ketolithocholic acid at pH 5.5 in a sodium-potassium-phosphate buffer containing NADPH or NADH. The products formed were analyzed by gas chromatography and gas chromatography-mass spectrometry. Results showed that chenodeoxycholic and ursodeoxycholic acids could be formed from 7-ketolithocholic acid by human liver enzyme(s). The enzyme(s) required NADPH but not NADH as coenzyme and was localized largely in the microsomes. The conjugated 7-ketolithocholic acid, especially the taurine conjugated, was predominantly reduced to chenodeoxycholic acid, whereas the unconjugated 7-ketolithocholic acid was not reduced well to either chenodeoxycholic acid or ursodeoxycholic acid. Thus the reduction of 7-ketolithocholic acid by human liver enzyme(s) was found to be dependent on whether the substrate was conjugated or not.
Amuro
Y
Y
Third Department of Internal Medicine, Hyogo College of Medicine, Japan.
Yamade
W
W
Kudo
K
K
Yamamoto
T
T
Hada
T
T
Higashino
K
K
D002635:Chenodeoxycholic Acid / Q000378:metabolism; D002849:Chromatography, Gas; D008401:Gas Chromatography-Mass Spectrometry; D005998:Glycine / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008095:Lithocholic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D013654:Taurine / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000378:metabolism
D002635:Chenodeoxycholic Acid; D009243:NAD; D013654:Taurine; C023020:7-ketolithocholic acid; D009249:NADP; D008095:Lithocholic Acid; D014580:Ursodeoxycholic Acid; D005998:Glycine