Conjugation with taurine prevents side-chain desaturation of ursodeoxycholic and β-muricholic acids in bile fistula rats
The metabolism of intravenously infused bile salts, tauroursodeoxycholate, tauro‐β‐muricholate and their corresponding unconjugated forms in the liver was investigated in bile salt‐depleted bile fistula rats. The biliary bile salt composition was determined by gas chromatography–mass spectrometry us...
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Published in | Fundamental & clinical pharmacology Vol. 18; no. 4; pp. 457 - 464 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Science Ltd
01.08.2004
Blackwell |
Subjects | |
Online Access | Get full text |
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Summary: | The metabolism of intravenously infused bile salts, tauroursodeoxycholate, tauro‐β‐muricholate and their corresponding unconjugated forms in the liver was investigated in bile salt‐depleted bile fistula rats. The biliary bile salt composition was determined by gas chromatography–mass spectrometry using chemical positive ionization and electron‐impact methods. For an infusion rate of 2 μmol/min/kg, all bile salts were efficiently secreted in bile, inducing similar choleresis. Only tauroconjugated bile salts were recovered; no glucuronide or glyco derivatives were detected. The infusion of free ursodeoxycholate led to the appearance of a metabolite identified as a Δ22 derivative (12%). A similar biotransformation rate (11%) was observed following free β‐muricholate infusion. In contrast, no metabolite was observed after infusion of the tauroconjugated form of ursodeoxycholate and β‐muricholate. The unsaturation process probably depends on the availability of the carboxyl group for the starting step of the β‐oxidation mechanism. In conclusion, the current in vivo study demonstrates a hepatic origin for Δ22 bile salts. It also shows that free bile salts were sensitive to Δ22 formation while conjugation with taurine totally prevented the side‐chain oxidation of the two 7β‐hydroxylated bile salts. |
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Bibliography: | ark:/67375/WNG-RVF112SQ-C ArticleID:FCP266 istex:CA58399ABC9B5470D645DD51639320FE3D02FE37 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0767-3981 1472-8206 |
DOI: | 10.1111/j.1472-8206.2004.00266.x |