5 beta-hydroxylation by the liver. Identification of 3,5,7-trihydroxy nor-bile acids as new major biotransformation products of 3,7-dihydroxy nor-bile acids in rodents.
24-Norursodeoxycholic acid (nor-UDCA), when administered into the anesthetized biliary fistula hamster or injected into the perfusate of an isolated liver, was hydroxylated at C-5 to give 5 beta-hydroxynorursodeoxycholic acid 2 (3 alpha,5,7 beta-trihydroxy-24-nor-5 beta-cholan-23-oic acid), which was secreted into bile mainly as such. Similarly, 24-norchenodeoxycholic acid (nor-CDCA) was 5 beta-hydroxylated to give 5 beta-hydroxynor-chenodeoxycholic acid 4 (3 alpha,5,7 alpha-trihydroxy-24-nor-5 beta-cholan-23-oic acid), which was also secreted into bile without appreciable further biotransformation. The site of hydroxylation was assigned by 13C and 1H NMR and mass spectrometry. 5-Hydroxylation was a major biotransformation pathway at physiological bile acid loads. 5-Hydroxylation of UDCA also occurred in the perfused rat liver but to a lesser extent. 5-Hydroxylation of nor-UDCA was not observed in rabbit, dog, or man, indicating that its formation is species-specific. 5-Hydroxylation of nor-CDCA and nor-UDCA is the first reported example of hydroxylation of a tertiary carbon atom of bile acids. Nor-dihydroxy bile acids appear to be useful for the detection of minor hydroxylation pathways, because their prolonged hepatobiliary retention exposes them repeatedly to hydroxylases present in the hepatobiliary system.
Department of Medicine, University of California, San Diego, La Jolla 92093.
C D
CD
Schteingart
L R
LR
Hagey
K D
KD
Setchell
A F
AF
Hofmann
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001652:Bile Ducts / Q000502:physiology; D001711:Biotransformation; D002250:Carbon Radioisotopes; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D006224:Cricetinae; D004285:Dogs; D008401:Gas Chromatography-Mass Spectrometry; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes; D013654:Taurine / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000031:analogs & derivatives* / Q000378:metabolism
D001647:Bile Acids and Salts; D002250:Carbon Radioisotopes; D013431:Sulfates; D013462:Sulfur Radioisotopes; D002635:Chenodeoxycholic Acid; D013654:Taurine; D014580:Ursodeoxycholic Acid; C081330:24-norchenodeoxycholic acid; C081331:24-norursodeoxycholic acid; D005947:Glucose