Hepatic bile acid uptake: effect of conjugation, hydroxyl and keto groups, and albumin binding.
Hepatic extraction of trihydroxy (free, glyco- and tauro-conjugated) dihydroxy, and monohydroxy bile acids has been evaluated in single pass liver perfusion experiments in rats. The percentage of each bile acid bound to albumin was also evaluated by equilibrium dialysis. Conjugation increased bile acid liver extraction, without relevant differences in the percentage of bile acid bound to albumin. Among the free bile acids, trihydroxy bile acids were more efficiently cleared by the liver than the dihydroxy acids, and the latter more than monohydroxy bile acids. 7-Ketolithocholic acid uptake was slightly less than that of cholic acid. Conversely, among dihydroxy bile acids, the percentage of the bile acid bound to albumin decreased from lithocholic acid to cholic acid. Decreasing the albumin concentration in the medium, and hence the fraction of the bile acid bound to albumin, resulted in an increase in bile acid liver extraction. Therefore besides differences in the chemical structure of bile acids, the extent of bile acid-albumin binding may be a determinant in bile acid liver uptake.
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D003956:Dialysis; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D010101:Oxygen Consumption; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism; D013997:Time Factors
D001647:Bile Acids and Salts; D012709:Serum Albumin