Studies on an Hepatic Membrane Receptor Specific for the Binding and Catabolism of Serum Glycoproteins
The development of a new concept for the role of the carbohydrate moiety in regulating the serum survival time of plasma glyco-proteins has been described in a recent review (3). Briefly, treatment with neuraminidase to remove sialic acid from circulating glycoproteins, followed by oxidation with galactose oxidase and reduction with KB3H4, introduced a tritum atom into carbon-6 of the terminal galactose residues (11). Upon injection of the resulting radioactive asialoglycoprotein into rabbits, the serum was promptly cleared of radioactivity and the intact macromolecule was recovered from the liver within 15 minutes after injection (10). The rapidity of removal was dependent upon the integrity of the exposed galactose; enzymatic oxidation by galactose oxidase or removal by hydrolysis with 3-galactosidase diminished the rate of hepatic uptake and resulted in an increased serum survival time approaching that of the fully sialylated control (10). More specifically, replacement of the deficient sialic acid residues, by incubation of the asialoglycoprotein with sialyltransferase in the presence of CMP-sialic acid, restored the original serum survival time (6). From the foregoing study, it became clear that hydrolysis of only a small fraction of the total sialic acid residues was sufficient for the liver to recognize and remove the entire protein (17) which was subsequently shown to be catabolized in the hepatic lysosomes (4). The generality of this phenomenon was demonstrated by the injection into rats of the asialo derivatives of a number of plasma proteins such as orosomucoid, fetuin, haptoglobin, ceruloplasmin and α2 -macroglo-bulin. In each case, the desialylated material disappeared rapidly from the circulation and accumulated in the liver (9). Competitive inhibition of hepatic uptake.was shown by the simultaneous injection of tracer amounts of [64 Cu] asialoceruloplasmin and substantive amounts of the above listed desialylated proteins or the glycopeptides derived from them.Uptake was not blocked by either the fully sialylated proteins or their corresponding glycopeptides (9).
KeywordsSialic Acid Lysosomal Storage Disease Sialic Acid Residue Galactose Oxidase Serum Glycoprotein
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