The Synthesis of Taurocholic and Glycocholic Acids in Human Liver Homogenates and Subcellular Fractions in Obstructive Jaundice

Abstract

The synthesis of taurocholic and glycocholic acids was studied in the whole homogenate and in subcellular fractions of livers from 18 patients operated on for cholestasis and compared with a control material with clinically normal liver function. A considerable decrease of synthesis of cholic acid conjugates was found in icteric homogenates, while no significant alteration of the synthesis was found in subcellular fractions containing the bile acid activating and transferring enzyme. The synthesis of cholic acid conjugates in icteric homogenates showed an inverse significant correlation to serum bilirubin values. Cholic acid conjugates added in vitro inhibited the synthesis of conjugates in homogenates and subcellular fractions. Bilirubin added in vitro brought about a significant decrease in synthesis of conjugates in homogenates but no changes of synthesis in the subcellular fractions mentioned. Soluble fraction as well as isolated mitochondria obtained from icteric human liver inhibited the synthesis of conjugates in microsome fraction and in combined microsome fraction and L-fraction. Oligomycin significantly increased the synthesis of conjugates in icteric homogenates but did not influence the synthesis in the mentioned subcellular fractions from icteric livers, or in homogenates from livers with clinically normal function. In no case, however, did oligomycin raise the synthesis of bile acid conjugates in icteric homogenate to that of controls. It is suggested that the bile acid conjugating enzyme system is intact in cases of cholestasis of short duration (<14 days) and that the decreased synthesis of conjugates in icteric homogenates might be the result of a product inhibition of the conjugation reaction by retained bile acid conjugates and of stimulated mitochondrial ATPase activity caused by retention of bile components.