Bile acid metabolism during development: metabolism of lithocholic acid in human fetal liver.

The metabolism of [24-14C]lithocholic acid was studied in the microsomal fraction of fetal human liver homogenates. Fetal livers were obtained at legal abortions performed between wk 14 and 24. Product formation was analyzed by thin-layer chromatography, liquid chromatography, and gas chromatography-mass spectrometry. From wk 14 lithocholic acid was hydroxylated in several positions. Hyodeoxycholic acid (3 alpha,6 alpha-dihydroxy-5 beta-cholanoic) and 1 beta,3 alpha-dihydroxy-5 beta-cholanoic acid were identified among the products. The 3 beta-isomer of the former acid, 6 alpha-hydroxy-3-oxo-5 beta-cholanoic acid and a 2-hydroxylithocholic acid were tentatively identified. Two other metabolites carried a hydroxyl group in an unknown position, one of them probably at an angular methyl group. The highest total conversions per mg of microsomal protein were obtained with preparations from 18 wk fetuses. The results are discussed with particular reference to the role of lithocholic acid in fetal hepatotoxicity.