Bile acid synthesis in man. In vivo activity of the 25-hydroxylation pathway

During biosynthesis of bile acid, carbons 25-26-27 are re-moved from the cholesterol side-chain. Side-chain oxidation begins either with hydroxylation at the 26-position, in which case the three-carbon fragment is released as propionic acid, or with hydroxylation at the 25-position, in which case the three-carbon fragment is released as acetone. We have previously shown in the rat that the contribution of the 25-hydroxylation pathway can be quantitated in vivo by measuring production of 1'4Cjacetone from I'4C126-cholesterol. In the present study, we adapted this method to human subjects. 4 d after oral adminis-tration of 100 gCi of ['4Cj26-cholesterol and 1 d after beginning a constant infusion of 16.6 Mmol/min unlabeled acetone, three men and two women underwent breath collections. Expired acetone was trapped and purified as the 2,4 dinitrophenylhy-drazine derivative. '4C02 was trapped quantitatively using phenethylamine. Specific activity of breath acetone was multi-plied by the acetone infusion rate to calculate production of 1'4Ciacetone. ['4CiAcetone production averaged 4.9 % of total release of '4C from 1'4(126-cholesterol, estimated by "CO2 output. The method was validated by showing that ['4qacetone production from I'4Ciisopropanol averaged 86.9 % of the i'4Ci-isopropanol infusion rate. We conclude that in man, as in the rat, the 25-hydroxylation pathway accounts for < 5 % of bile acid synthesis