Metabolism of 3 alpha, 7 alpha-dihydroxy-7 beta-methyl-5 beta-cholanoic acid and 3 alpha, 7 beta-dihydroxy-7 alpha-methyl-5 beta-cholanoic acid in hamsters.
The metabolic fate of the bile acid analogs, 3 alpha, 7 alpha-dihydroxy-7 beta-methyl-5 beta-cholanoic acid and 3 alpha, 7 beta-dihydroxy-7 alpha-methyl-5 beta-cholanoic acid, was investigated and compared with that of chenodeoxycholic acid in hamsters. Both bile acid analogs were absorbed rapidly from the intestine and excreted into bile at rates similar to that of chenodeoxycholic acid. In the strain of hamster studied, the biliary bile acids were conjugated with both glycine and taurine. After continuous intravenous infusion, chenodeoxycholic acid and the analogs became the major bile acid constituents in bile. After oral administration of a single dose of these compounds, fecal analysis revealed the existence of unchanged material (25-35%) as well as considerable amounts of metabolites (65-75%). The major metabolites excreted into feces were more polar than the starting material and were tentatively identified as trihydroxy-7-methyl compounds by radioactive thin-layer chromatography. However, monohydroxy compounds were also found in the fecal extracts. These results show that chenodeoxycholic acid and ursodeoxycholic acid with a methyl group at the 7-position are more resistant to bacterial 7-dehydroxylation than the normally occurring bile acids and that a certain proportion of these analogs is hydroxylated to give the corresponding trihydroxy compound(s). In a control experiment, about 5% of administered chenodeoxycholic acid was metabolized to a trihydroxy bile acid, but most of the compound (95%) was transformed into lithocholic acid.
D000818:Animals; D001646:Bile / Q000378:metabolism; D002793:Cholic Acids / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D006224:Cricetinae / Q000378:metabolism*; D005243:Feces / Q000032:analysis; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism; D008297:Male; D008647:Mesocricetus / Q000378:metabolism*; D014580:Ursodeoxycholic Acid / Q000031:analogs & derivatives*
D002793:Cholic Acids; D014580:Ursodeoxycholic Acid; C041636:3,7-dihydroxy-7-methylcholanoic acid