title: Formation, absorption, and biotransformation of delta 6-lithocholenic acid in humans.
abstract: delta 6-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 delta 6-[24-14C]lithocholenic acid was biotransformed in vitro in feces within 30 s. After colonic instillation of delta 6-[24-14C]lithocholenic acid, 50% of the radioactivity appeared in bile acids, most of it in lithocholic acid, within 3 h. Jejunal perfusions with delta 6-[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 delta 6-lithocholenic acid was identified in bile. One hour after intravenous injection of delta 6-[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 delta 6-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 delta 6-lithocholenic acid as a new intermediate in formation of lithocholic acid. Finally, the studies showed that a small portion of delta 6-lithocholenic acid is excreted as a sulfated glycine conjugate in bile.
authors.affiliation: Department of Medicine, George Washington University Medical Center, Washington, DC 20037.
authors.forename: M
authors.initials: M
authors.lastname: Malavolti
authors.forename: H
authors.initials: H
authors.lastname: Fromm
authors.forename: E
authors.initials: E
authors.lastname: Nsien
authors.forename: K D
authors.initials: KD
authors.lastname: Setchell
authors.forename: M B
authors.initials: MB
authors.lastname: Albert
authors.forename: B
authors.initials: B
authors.lastname: Cohen
authors.forename: S
authors.initials: S
authors.lastname: Ceryak
mesh_terms: D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D005243:Feces / Q000737:chemistry; D006801:Humans; D007408:Intestinal Absorption; D008095:Lithocholic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D012016:Reference Values; D014580:Ursodeoxycholic Acid / Q000494:pharmacology
chemical_list: D002635:Chenodeoxycholic Acid; C046457:3-hydroxy-6-cholen-24-oic acid; D008095:Lithocholic Acid; D014580:Ursodeoxycholic Acid