Interaction of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, an inhibitor of plasma protein binding in uraemia, with human albumin.

The furan dicarboxylic acid 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (5-propyl FPA) accumulates in uraemic plasma and is a potent inhibitor of the binding of other anionic ligands to albumin. The interaction of 5-propyl FPA with human albumin has been investigated by equilibrium dialysis at 37 degrees and pH 7.4. Analysis of the binding data on the basis of a two-site model gave binding parameters of n1 = 0.6 and K1 = 4.8 x 10(6) M-1 for the primary binding site. 5-Propyl FPA binding was observed to decrease as the pH was raised from 6.4 to 8.3 which emphasizes the need for pH control of whole plasma or serum. Temperature, however, had little effect on binding as assessed by equilibrium dialysis at 10 degrees, 25 degrees and 37 degrees. The high affinity of 5-propyl FPA for albumin explains its retention in uraemic plasma, its potency as a binding inhibitor and points to active tubular secretion as the mechanism by which it is normally excreted by the kidney.