The Role of Sialic Acid in Determining the Survival of Glycoproteins in the Circulation

TLDR

The study examined a panel of plasma glycoproteins—including orosomucoid, fetuin, ceruloplasmin, haptoglobin, α2‑macroglobulin, thyroglobulin, lactoferrin, and the gonadotropins hCG and FSH—to assess their clearance dynamics. The results demonstrate that terminal sialic acid residues protect circulating glycoproteins from rapid hepatic clearance; desialylated proteins (except transferrin) were cleared quickly and competitively inhibited hepatic uptake of ceruloplasmin, whereas fully sialylated proteins did not affect uptake.

Abstract

Evidence is presented to indicate a generalized role for the terminal sialic acid residues of circulating glycoproteins. Upon injection into rats, all of the desialylated plasma proteins tested, with the exception of transferrin, were promptly removed from the circulation and were recovered from the liver. The materials examined included orosomucoid, fetuin, ceruloplasmin, haptoglobin, α2-macroglobulin, thyroglobulin, lactoferrin, and the two gonadotropic hormones, human chorionic gonadotropin and follicle-stimulating hormone. Competitive inhibition of hepatic uptake was demonstrated by the injection of tracer amounts of 64Cu-ceruloplasmin together with substantive amounts of the above-mentioned desialylated proteins or the glycopeptides derived from them. Uptake was not inhibited by the fully sialylated protein or their glycopeptides.