Displacement of albumin-bound bilirubin by free fatty acids. Implications for neonatal hyperbilirubinemia

Abstract

The interaction of bilirubin, linoleate and human plasma albumin was investigated in an isolated model system, designed to evaluate the competitive effect of free fatty acids (FFA) on the binding of unconjugated bilirubin by albumin. Increasing amounts of linoleate were added to bilirubin-albumin solutions at a constant molar ratio, and the mixtures passed through Sephadex G-25 columns to absorb the displaced bilirubin, which was then eluted and determined. In solutions with molar ratio bilirubin/albumin of 0.5 or 1.0 no displacement was evident when the molar ratio of linoleate relative to albumin was below 5. Above molar ratio of linoleate/albumin of 6, free bilirubin in the system rose sharply. In solutions with molar ratio bilirubin/albumin of 1.8, bilirubin dissociated from albumin markedly when the molar ratio of linoleate relative to albumin approached 4. Thus, the displacement of bilirubin starts only after most of the FFA binding sites on albumin with high association constants become saturated, and the competition involves mainly multiple binding sites with low association constants. In two groups of infants without or with hyperbilirubinemia requiring exchange transfusion, the molar ratio FFA/albumin in plasma ranged from 1.07 to 2.37. These values are much lower than those initiating the displacement of bilirubin in the in vitro system. The significance of FFA in causing shifts of bilirubin between intra- and extravascular pools is briefly discussed. It is suggested that FFA in neonates, although elevated, do not seem to reach concentrations, relative to albumin, which are effective in bilirubin dissociation.