Hepatic receptor that specifically binds oligosaccharides containing fucosyl alpha1 leads to 3 N-acetylglucosamine linkages.
Evidence is presented suggesting that hepatocytes contain a receptor that binds glycoproteins specifically through fucose in alpha1-->3 linkage to N-acetylglucosamine. Human lactoferrin, which contains this type of linkage, is rapidly cleared from the circulation of mice after intravenous injection, and greater than 90% of the injected material is found in hepatocytes. Binding of lactoferrin is mediated through its carbohydrate groups, since its clearance is prolonged after periodate oxidation or after its oligosaccharide groups are extensively degraded with glycosidases. In addition, glycopeptides from lactoferrin inhibit lactoferrin clearance. That lactoferrin clearance is mediated through binding to its fucosyl groups is suggested for several reasons. First, transferrin and asialotransferrin, whose oligosaccharide groups are essentially structurally identical to those of lactoferrin but devoid of fucose, are not cleared on intravenous injection. Second, when fucose is incorporated into asialotransferrin by alpha1-->3 N-acetylglucosamine fucosyl transferase, the resulting fucosylated derivative is cleared rapidly. Neither mannan nor derivatives of orosomucoid that are cleared by binding to receptors for galactose, N-acetylglucosamine, or mannose, inhibit clearance of lactoferrin although clearance is inhibited by fucoidin. Finally, glycoproteins containing fucose in alpha1 --> 2 linkage to galactose or alpha1 --> 6 linkage to N-acetylglucosamine do not inhibit lactoferrin clerance by the liver. Since clearance of other glycoproteins, such as human lactoperoxidase, also appears to be mediated through binding to the same hepatocyte receptor as lactoferrin, it is concluded that the fucose-specific receptor studied here may fulfill other functions than binding lactoferrin. Preliminary studies with liver homogenates and detergent extracts of liver show binding in vitro.
D000117:Acetylglucosamine / Q000378:metabolism; D000818:Animals; D005260:Female; D005643:Fucose / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D007781:Lactoferrin / Q000378:metabolism; D007784:Lactoperoxidase / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D009844:Oligosaccharides / Q000378:metabolism; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism*; D013329:Structure-Activity Relationship
D006023:Glycoproteins; D009844:Oligosaccharides; D011955:Receptors, Drug; D005643:Fucose; D007784:Lactoperoxidase; D007781:Lactoferrin; D000117:Acetylglucosamine