Title

Formation, absorption, and biotransformation of Δ6-lithocholenic acid in humans

Document Type

Journal Article

Publication Date

1-1-1993

Journal

American Journal of Physiology - Gastrointestinal and Liver Physiology

Volume

264

Issue

1 27-1

Keywords

7-ketolithocholic acid; bile acid metabolism; chenodeoxycholic acid; lithocholic acid; unsaturated bile acids; ursodeoxycholic acid

Abstract

Δ6-Lithocholenic acid was identified in small amounts in fecal samples in vitro after incubation with ursodeoxycholic acid and in vivo in controls and after chenodeoxycholic and ursodeoxycholic acid ingestion. Fourteen to 45.0% of Δ6-[24-14C]lithocholenic acid was biotransformed in vitro in feces within 30 s. After colonic instillation of Δ6-[24-14C]lithocholenic acid, 50% of the radioactivity appeared in bile acids, most of it in lithocholic acid, within 3 h. Jejunal perfusions with Δ6-[24-14C]lithocholenic acid showed 33-92% absorption. One hour after jejunal instillation of 1 mmol, 4.4- 27.5% of the biliary radioactivity was found in ursodeoxycholic, chenodeoxycholic, lithocholic, and 7-ketolithocholic acids. A sulfated glycine conjugate of Δ6-lithocholenic acid was identified in bile. One hour after intravenous injection of Δ6-[24-14C]lithocholenic acid, 40.1-42.6% of biliary radioactivity appeared in 7-ketolithocholic, chenodeoxycholic, lithocholic/isolithocholic, and ursodeoxycholic acids. The studies show that Δ6-lithocholenic acid is 1) formed in colonic lumen from chenodeoxycholic and ursodeoxycholic acids, 2) well absorbed in small intestine, and 3) biotransformed in both the colonic lumen and liver. The studies also identified Δ6-lithocholenic acid as a new intermediate in formation of lithocholic acid. Finally, the studies showed that a small portion of Δ6- lithocholenic acid is excreted as a sulfated glycine conjugate in bile.

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