Hepatic Binding Protein: The Galactose-Specific Receptor of Mammalian Hepatocytes

Abstract

The membranes of the liver cell have been described as a protein mosaic within a lipid bilayer. Among the various pieces in this design are receptor proteins capable of recognizing and binding specific ligands. These receptors define much of the differentiated state of hepatocytes providing them with many specific functions. One of the most extensively studied of these receptor proteins is the hepatic binding protein or HBP. This membrane glycoprotein is responsible for the endocytosis of galactose-terminating glycoproteins leading to their lysosomal catabolism. While no physiologic function has yet been ascribed to HBP, its study has provided many insights into the biology and pathobiology of the liver. DISCOVERYThe path that led to discovery of HBP began with the development of a novel procedure to incorporate tritium selectively into the galactosyl residues of serum glycoprotein (1). Since most serum glycoproteins' carbohydrate moieties terminate in sialic acid, this residue was enzymatically removed to expose the penultimate galactose. The desialylated glycoproteins were then treated with galactose oxidase to yield an active aldehyde group in their galactosyl residues which could be reduced with tritiated borohydride. Application of this procedure to the serum copper-protein, ceruloplasmin, yielded a preparation which was indistinguishable from the native protein except, of course, for the absence of sialic acid. However, when this desialylated glycoprotein was injected, it no longer was viable in the circulation (2).The penultimate galactosyl residues, exposed by removal of sialic acid, were shown to be the critical determinants of this rapid clearance phenomena (3, 4). Enzymatic oxidation or removal of the terminal galactosyl residues significantly prolonged the intravascular survival of desialylated ceruloplasmin. The unique nature of this model was extended beyond galactose-directed clearance by the observation that sequestration of desiAddress reprint requests to: Richard J. Stockert, Ph.D., Ullmann, Room 517,

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