Metabolism of lithocholic acid in the rat: formation of lithocholic acid 3-O-glucuronide in vivo

J. M. Little, P. Zimniak, K. E. Shattuck, R. Lester, A. Radominska

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Abstract

Milligram amounts of [3β-3H]lithocholic (3α-hydroxy-5β-cholanoic) acid were administered by intravenous infusion to rats prepared with a biliary fistula. Analysis of sequential bile samples by thin-layer chromatography (TLC) demonstrated that lithocholic acid glucuronide was present in bile throughout the course of the experiments and that its secretion rate paralleled that of total isotope secretion. Initial confirmation of the identity of this metabolite was obtained by the recovery of labeled lithocholic acid after β-glucuronidase hydrolysis of bile samples. For detailed analysis of biliary metabolites of [3H]lithocholic acid, pooled bile samples from infused rats were subjected to reversed-phase chromatography and four major labeled peaks were isolated. After complete deconjugation, the two major compounds in the combined first two peaks were identified as murideoxycholic (3α,6β-dihydroxy-5β-cholanoic) and β-muricholic (3α,6β,7β-trihydroxy-5β-cholanoic) acids and the third peak was identified as taurolithocholic acid. The major component of the fourth peak, after isolation, derivatization (to the methyl ester acetate), and purification by high pressure liquid chromatography (HPLC), was positively identified by proton nuclear magnetic resonance as lithocholic acid 3α-O-(β-D-glucuronide). These studies have shown, for the first time, that lithocholic acid glucuronide is a product of in vivo hepatic metabolism of lithocholic acid in the rat.

Original languageEnglish (US)
Pages (from-to)615-622
Number of pages8
JournalJournal of Lipid Research
Volume31
Issue number4
StatePublished - Jun 7 1990
Externally publishedYes

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Keywords

  • Bile acid
  • cholestasis
  • glucuronide

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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