Conjugation with taurine prevents side-chain desaturation of ursodeoxycholic and beta-muricholic acids in bile fistula rats.
The metabolism of intravenously infused bile salts, tauroursodeoxycholate, tauro-beta-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 micromol/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 Delta22 derivative (12%). A similar biotransformation rate (11%) was observed following free beta-muricholate infusion. In contrast, no metabolite was observed after infusion of the tauroconjugated form of ursodeoxycholate and beta-muricholate. The unsaturation process probably depends on the availability of the carboxyl group for the starting step of the beta-oxidation mechanism. In conclusion, the current in vivo study demonstrates a hepatic origin for Delta22 bile salts. It also shows that free bile salts were sensitive to Delta22 formation while conjugation with taurine totally prevented the side-chain oxidation of the two 7beta-hydroxylated bile salts.
Faculté de Pharmacie, UPRES EA 3286, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 5, France.
Mustapha
M
Guitaoui
Michel
M
Parquet
Claude
C
Aubert
Anne-Marie
AM
Montet
Jean-Claude
JC
Montet
D000818:Animals; D001647:Bile Acids and Salts / Q000172:deficiency / Q000378:metabolism*; D001658:Biliary Fistula / Q000378:metabolism*; D001711:Biotransformation; D008401:Gas Chromatography-Mass Spectrometry; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000494:pharmacology*
D001647:Bile Acids and Salts; D013654:Taurine