Metabolism of the bile acid analogues 7 beta-methyl-cholic acid and 7 alpha-methyl-ursocholic acid.
The metabolism of two new bile acid analogues, 7 beta-methyl-cholate and 7 alpha-methyl-ursocholate, was compared with that of cholate in the hamster. After intraduodenal administration of 14C-labeled compounds into bile fistula hamsters, radioactivity was exclusively recovered in bile; the more hydrophobic bile acid was absorbed more rapidly. Hepatic extraction of intravenously infused compounds was efficient and administered analogues became major biliary bile acids. Amidation of cholate was essentially complete, whereas 39% of 7 beta-methyl-cholate and 65% of 7 alpha-methyl-ursocholate were secreted in unconjugated form. After intragastric administration of the compounds, radioactivity was quantitatively recovered in feces. Cholate was 7-dehydroxylated to deoxycholate, whereas 31% of 7 beta-methyl-cholate and 78% of 7 alpha-methyl-ursocholate were recovered unchanged. Fifty percent of 7 beta-methyl-cholate and 15% of 7 alpha-methyl-ursocholate were transformed into ketonic derivatives, without loss of the 7-hydroxyl group. It is concluded that the introduction of the 7-methyl group did not interfere with intestinal absorption, hepatic extraction, and biliary secretion but did affect enzymatic amidation and bacterial 7-dehydroxylation of the analogues.
D000818:Animals; D001711:Biotransformation; D002250:Carbon Radioisotopes; D019826:Cholic Acid; D002793:Cholic Acids / Q000008:administration & dosage / Q000378:metabolism*; D006224:Cricetinae; D004333:Drug Administration Routes; D004386:Duodenum; D005998:Glycine / Q000378:metabolism; D007262:Infusions, Intravenous; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D013270:Stomach; D013654:Taurine / Q000378:metabolism
D002250:Carbon Radioisotopes; D002793:Cholic Acids; C051656:3,7,12-trihydroxy-7-methylcholanoic acid; D013654:Taurine; D019826:Cholic Acid; C030712:ursocholic acid; D005998:Glycine