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

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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 - 1990
Externally publishedYes

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Lithocholic Acid
Glucuronides
Metabolism
Bile
Rats
Metabolites
Taurolithocholic Acid
Nuclear magnetic resonance
High pressure liquid chromatography
Biliary Fistula
Thin layer chromatography
Glucuronidase
Reverse-Phase Chromatography
Thin Layer Chromatography
Chromatography
Intravenous Infusions
Isotopes
Purification
Protons
Hydrolysis

Keywords

  • Bile acid
  • cholestasis
  • glucuronide

ASJC Scopus subject areas

  • Endocrinology

Cite this

Metabolism of lithocholic acid in the rat : formation of lithocholic acid 3-O-glucuronide in vivo. / Little, J. M.; Zimniak, P.; Shattuck, Karen; Lester, R.; Radominska, A.

In: Journal of Lipid Research, Vol. 31, No. 4, 1990, p. 615-622.

Research output: Contribution to journalArticle

Little, JM, Zimniak, P, Shattuck, K, Lester, R & Radominska, A 1990, 'Metabolism of lithocholic acid in the rat: formation of lithocholic acid 3-O-glucuronide in vivo', Journal of Lipid Research, vol. 31, no. 4, pp. 615-622.
Little, J. M. ; Zimniak, P. ; Shattuck, Karen ; Lester, R. ; Radominska, A. / Metabolism of lithocholic acid in the rat : formation of lithocholic acid 3-O-glucuronide in vivo. In: Journal of Lipid Research. 1990 ; Vol. 31, No. 4. pp. 615-622.
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