STUDIES IN KERNICTERUS. I. THE PROTEIN BINDING OF BILIRUBIN*

Abstract

Protein binding of bilirubin was studied in serum from 20 patients with hyperbilirubinemia of various causestin the neonatal period. Alterations in the degree of protein binding of the serum bilirubin were produced by the addition of various organic anions used in clinical medicine. Sulfadiazine, sulfanilic acid, sulfisoxazole, and salicylate were increasingly effective in producing dissociation of protein-bound bilirubin. Loss of protein-bound bilirubin was demonstrated by decrease in optical absorption at 460 dim, the absorption maximum of protein-bound bilirubin, and by simultaneous increase in absorption at 420 m/x, the absorption maximum of free bilirubin. Similar results were found with a model serum of bovine albumin or with crystalline human albumin and bilirubin. The dissociation induced appeared to result from competition between the anions and bilirubin for a common locus on the albumin molecule. The bilirubin dissociated from serum albumin was diffusible and could enhance the likelihood of clinical kernicterus. The diffusible bilirubin concentration rather than total bilirubin concen-tration of extracellular fluids, determines how much bilirubin will get into cells. Consequently, kernicterus may occur at low plasma bilirubin concentrations.