Journal of Lipid Research, Vol 31, 615-622, Copyright © 1990 by Lipid Research, Inc.

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

JM Little, P Zimniak, KE Shattuck, R Lester and A Radominska
Department of Medicine, University of Arkansas for Medical Science, Little Rock 72205.

Milligram amounts of [3 beta-3H]lithocholic (3 alpha-hydroxy-5 beta- 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 beta-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 (3 alpha, 6 beta-dihydroxy- 5 beta-cholanoic) and beta-muricholic (3 alpha, 6 beta, 7 beta- trihydroxy-5 beta-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 3 alpha-O-(beta-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.
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