Interaction of hepatic asialoglycoprotein receptor with asialoorosomucoid and galactolyzed lysosomal alpha-glucosidase.
An asialoglycoprotein receptor was isolated from murine liver and purified more than 1600-fold using 2-fold affinity chromatography on asialoorosomucoid-Sepharose. The purified receptor did not interact with 125I-orosomucoid, but bound to 125I-asialoorosomucoid. The binding of the receptor to asialoorosomucoid was saturable. The dissociation constant of the receptor-asialoorosomucoid complex was 0.4 X 10(-9) M. The molecular mass of the receptor, as determined with the use of specific antibodies by the immunoblotting method, was 43 kDa. High concentrations of unlabeled asialoorosomucoid and of n-aminophenyl-beta-D-galactosyl derivatives of bovine serum albumin, ovalbumin and acid alpha-glucosidase from human liver inhibited the binding of the receptor to 125I-asialoorosomucoid almost completely. The binding of the receptor to 125I-galactolyzed alpha-glucosidase was pH-dependent, with the pH optimum at 8.0-9.0. It was shown that, as in the case of 125I-asialoorosomucoid, the binding of the 125I-galactosyl derivative of alpha-glucosidase occurred in the presence of Ca2+ and was inhibited by N-acetylgalactosamine. Glycoproteins containing galactose as a terminal residue inhibited the interaction of the receptor with 125I-galactolyzed alpha-glucosidase. The possibility of directed transport of the galactolyzed alpha-glucosidase derivative into parenchymous liver cells using receptor-mediated endocytosis is discussed.
D000116:Acetylgalactosamine / Q000378:metabolism; D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D002846:Chromatography, Affinity; D005959:Glucosidases / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice; D008970:Molecular Weight; D009961:Orosomucoid / Q000031:analogs & derivatives* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D000520:alpha-Glucosidases / Q000378:metabolism*
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D009961:Orosomucoid; D011971:Receptors, Immunologic; C017030:asialoorosomucoid; D005959:Glucosidases; D000520:alpha-Glucosidases; D000116:Acetylgalactosamine