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

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 3 alpha, 7 alpha, 12 alpha-trihydroxy-5(alpha and beta)-cholanoic, 3 alpha, 7 alpha-dihydroxy-5(alpha and beta)-cholanoic and 3 alpha, 6 beta, 7 alpha-trihydroxy-5 beta-cholanoic acids; sulphates of 3(alpha and beta), 7 alpha, 12 alpha-trihydroxy-5 alpha-cholanoic, and 3(alpha and beta), 7 alpha-dihydroxy-5 alpha-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 [1,1-2H]-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.