Ursodeoxycholic Acid, 7-Ketolithocholic Acid, and Chenodeoxycholic Acid Are Primary Bile Acids of the Nutria (Myocastor copus)

Abstract

Because ursodeoxycholic and chenodeoxycholic acids are interconverted in humans via 7-ketolithocholic acid, bile acid metabolism was studied in the nutria (Myocastor coypus), the bile of which is known to contain these three bile acids. Relative concentrations of ursodeoxycholic (37% +/- 20%), 7-ketolithocholic (33% +/- 17%), and chenodeoxycholic (17% +/- 9%) acids in gallbladder bile were unchanged by 5-20 h of complete biliary diversion (n = 7). Injection of either [14C]cholesterol, [14C]ursodeoxycholic, [14C]7-ketolithocholic acid, or a mixture of [7 beta-3H]chenodeoxycholic acid and [14C]chenodeoxycholic acid into bile fistula nutria demonstrated that all three bile acids can be synthesized hepatically from cholesterol, that they are interconverted sparingly (2%-5%) by the liver, but that 7-ketolithocholic acid is an intermediate in the hepatic transformation of chenodeoxycholic acid to ursodeoxycholic acid. An animal that had been fed antibiotics showed an unusually elevated concentration of ursodeoxycholic acid in gallbladder and hepatic bile, suggesting that bacterial transformation of ursodeoxycholic acid in the intestine may be a source of some biliary chenodeoxycholic acid and 7-ketolithocholic acid.