Molecular Pharmacology, Vol 7, 511-518, Copyright © 1971 by the American Society for Pharmacology and Experimental Therapeutics

Effect of Free Fatty Acid Concentration on the Transport and Utilization of Other Albumin-Bound Compounds: Hydroxyphenylazobenzoic Acid

¹ Departments of Internal Medicine and Biochemistry and the Clinical Research Center, University of Iowa, Iowa City, Iowa 52240

The purpose of this study was to determine whether changes in long-chain free fatty acid concentration would alter the transport and utilization of another organic ligand that was bound to human plasma albumin. Ehrlich ascites cells were incubated in medium containing human albumin, and the uptake of 2-(4'-hydroxyphenylazo)benzoic acid was measured relative to the free fatty acid concentration of the medium. As the molar ratio of free fatty acid to albumin was raised from 1 to 4, hydroxyphenylazobenzoic acid uptake by the cells increased. In contrast, cells "loaded" with large quantities of fatty acid took up no more hydroxyphenylazobenzoic acid from an albumin-free medium than did cells loaded with only small amounts of fatty acid. Equilibrium dialysis binding measurements indicated that the binding capacity of human albumin for hydroxyphenylazobenzoic acid decreased as the molar ratio of free fatty acid to albumin was raised. Therefore, it is likely that the free fatty acid-induced increase in hydroxyphenylazobenzoic acid uptake by the Ehrlich cells was due to displacement of this compound from strong to weaker albumin binding sites rather than to a direct effect of fatty acids on the cells. These results suggest that variations in the molar ratio of free fatty acid to albumin may influence the transport and utilization of other albumin-bound metabolites or drugs.