Asialoglycoproteins serve as ligands of the hepatic asialoglycoprotein receptor (ASGP-R) and induce down- modulation of the functional expression of the receptor without altering immunological integrity. The molecular basis for the phenomenon was investigated in well-differentiated human hepatoma cell lines (Hep G2). This ligand-induced moluation was found to be related to a decrease in protein-bound sialic acid. The low concentration of cell protein-bound sialic acid appears to be the result of the exogenous asialoglycoprotein, i.e. the ligands themselves, serving as substrates for sialotransferases. This results in a competition with the cell's own glycoproteins for the limited amount of sialic acid synthesis. This mechanism, in which the concentration of intracellular asialoprotein appears to act as modulator, may regulate the amount of asialoprotein that enters the cells.
