Metabolism in man of 7-ketolithocholic acid: precursor of cheno- and ursodeoxycholic acids

To define the metabolism of 7-ketolithocholic acid in man, studies were carried out in gallstone patients with normal liver function. 7-[24-14C]ketolithocholic acid or its glycine or taurine conjugates were injected intravenously, and the chemical form of radioactivity appearing in bile was determined to define hepatic biotransformation. To study intestinal absorption 7-[24-14C]ketolithocholic acid was infused into the jejunum and ileum, respectively, and the chemical form of radioactivity appearing in peripheral blood and bile was assessed. 7-Ketolithocholic acid was extensively reduced in the liver to chenic acid and, to lesser extent, to ursodeoxycholic acid. Hepatic reduction was similar for both unconjugated as well as glycine- and taurine-conjugated 7-ketolithocholic acid. 7-Ketolithocholic acid was well absorbed. There was no biotransformation in the small intestinal lumen or during absorption, because all radioactivity recovered from the lumen or in peripheral blood was in unchanged 7-ketolithocholic acid. Biotransformation products in bile after jejunal infusion were similar to those after intravenous injection. The studies indicate that 7-ketolithocholic acid is likely to be a physiological precursor of ursodeoxycholic acid in healthy man.