The fluorescence of 1-anilinio-8-naphthalenesulfonate (ANS) bound to human plasma albumin was enhanced when up to 2 moles of palmitate were added. Larger amounts of palmitate produced a progressive reduction in ANS fluorescene. Saturated and unsaturated fatty acids containing 14-18 carbon atoms produced similar biphasic effects on ANS fluorescence with human albumin. Fatty acids containing 10-12 carbon atoms produced only a reduction in ANS fluorescence, and those containing 2-8 carbon atoms had no effect. Similar results were obtained with canine albumin, whereas with bovine and rabbit albumins, fatty acids in all concentrations reduced ANS fluorescence. The tryptophan fluorescence of human albumin was decreased markedly by ANS, but not by palmitate. However, palmitate partially protected the tyrptophan fluorescence against quenching by potassium iodide. Equilibrium dialysis measurements indicated that ANS binding to human albumin was reduced when 3 or more moles of long-chain fatty acid were added per mole of albumin, suggesting that the decrease in ANA fluorescence produced by high concentrations of fatty acid was due to displacement of ANS from albumin. ANS binding was essentially unchanged when 1 or 2 moles of fatty acid were present. Therefore the enhancement in ANS fluorescence produced by low concentrations of fatty acid appears to result from a change in the interaction of ANS with albumin rather than from an increase in the amount of ANS that is bound The data obtained with this fluorescent model compound suggest that the binding of some drugs to albumin may be influenced by changes in the plasma free fatty acid concentration. Small increases, such as those which occur under ordinary physiological conditions, are likely to alter the molecular interactions between albumin and the drug without appreciably affecting the strength of drug binding. When the molar ratio of fatty acid to albumin approaches 3, however, a decrease in drug binding is likely to occur.
- Copyright ©, 1974, by Academic Press, Inc.