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.
Schteingart
C D
CD
Department of Medicine, University of California, San Diego, La Jolla 92093.
Hagey
L R
LR
Setchell
K D
KD
Hofmann
A F
AF
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