Formation of ursodeoxycholic acid from chenodeoxycholic acid in the human colon: studies of the role of 7-ketolithocholic acid as an intermediate.

The formation of ursodeoxycholic acid from che- nodeoxycholic acid and the role of 7-ketolithocholic acid as an intermediate in this biotransformation were studied in vitro in fecal incubations as well as in vivo in the human colon. (24- "C)-Labeled 7-ketolithocholic and chenodeoxycholic acids were studied at various concentrations, and the biotransfor- mation products were analyzed by thin-layer chromatography, gas-liquid chromatography, and mass spectrometry. There was rapid colonic conversion of 7-ketolithocholic acid to ur- sodeoxycholic acid and, to a lesser extent, to chenodeoxycholic acid. The reduction of 7-ketolithocholic to ursodeoxycholic acid proceeded significantly faster anaerobically and at acid pH than under aerobic and alkaline conditions. When che- nodeoxycholic acid was incubated in vitro or instilled into the colon, various amounts of 7-ketolithocholic and ursodeoxy- cholic acids were formed. The formation of 7-ketolithocholic acid was favored by alkaline conditi0ns.l Isotope dilution studies, in which trace amounts of laheled 7-ketolithocholic acid were incubated with unlabeled chenodeoxycholic acid, indicate 7-ketolithocholic acid to be the major intermediate in the intestinal bacterial conversion of chenodeoxycholic to ursodeoxycholic acid.-Fmmm, H., R. P. Sarva, and F. Baz- zoli. Formation of ursodeoxycholic acid from chenodeoxy- cholic acid in the human colon: studies of the role of 7-ke- tolithocholic acid as an intermediate. J. Lipid Res. 1983. 24 84 1-853.