Biosynthesis of 5α- and 5β-cholanoic acid derivatives during metabolism of [1,1- 2H]- and [2,2,2- 2H]ethanol in the rat

Abstract

Female bile fistula rats were given [1,1- 2H]ethanol in a single dose or [2,2,2- 2H]ethanol repeatedly for 24 h and incorporation of deuterium into the following bile acids was determined: taurine conjugates of 3α,7α,12α-trihydroxy-5(α and β)-cholanoic, 3α,7α-dihydroxy-5(α and β)-cholanoic and 3α,6β,7α-trihydroxy-5β-cholanoic acids; sulphates of 3(α and β),7α,12α-trihydroxy-5α-cholanoic, and 3(α and β),7α-dihydroxy-5α-cholanoic acids. The kinetics of deuterium incorporation from [2,2,2- 2H]ethanol was the same for all bile acids indicating that they were formed from a single pool of cholesterol. The labelling pattern of bile acids formed during metabolism of [1,1- H]-ethanol indicated that the hydrogen at C-5 was labelled in all bile acids. Taken together with previous results this indicates that 3-oxo-4-cholenoic acid is not an intermediate in the formation of allo bile acids. The results support the view that formation of allo bile acids via a mitochondrial pathway is of little importance in the bile fistula rat.