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 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 Δ 22 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 (3-oxidation mechanism. In conclusion, the current in vivo study demonstrates a hepatic origin for Δ 22 bile salts. It also shows that free bile salts were sensitive to Δ 22 formation while conjugation with taurine totally prevented the side-chain oxidation of the two 7β-hydroxylated bile salts.