[Chemical galactosylation of acid alpha-glucosidase to provide directed transport of the enzyme into lysosomes of liver parenchymal cells].
Chemical galactosylation of human liver tissue lysosomal alpha-glucosidase was carried out. As a result of the modification some physicochemical properties of the enzyme were altered, while its stability and catalytic activity were maintained. An ability of the galactosylated alpha-glucosidase to interact with asialoglycoprotein receptor from mice liver tissue was studied in vitro. The reaction required Ca2+. A specific inhibitor of the receptor, N-acetyl galactosamine, as well as high concentrations of native glycoproteins and neoglycoproteins containing terminal galactose inhibited the receptor binding of the 125I-galactosylated alpha-glucosidase. Native alpha-glucosidase was not bound with the receptor. Antireceptor antibodies inhibited similarly binding of both native ligand, asialoorosomucoid and the galactosylated alpha-glucosidase. These data on specific interaction between the galactosylated form of alpha-glucosidase and asialoglycoprotein receptor are discussed in connection with the problem of directed transport of the enzyme into liver parenchymatous cells by means of receptor-dependent endocytosis, which may be of importance in development of enzymotherapy of hereditary lysosomal enzymopathies.
Belen'kiĭ
D M
DM
D000818:Animals; D001692:Biological Transport; D005087:Glucan 1,4-alpha-Glucosidase / Q000378:metabolism* / Q000627:therapeutic use; D005959:Glucosidases / Q000378:metabolism*; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy; D006801:Humans; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology*; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000378:metabolism*; D000520:alpha-Glucosidases
D011956:Receptors, Cell Surface; C039707:galactose receptor; D005959:Glucosidases; D000520:alpha-Glucosidases; D005087:Glucan 1,4-alpha-Glucosidase
Khimicheskoe galaktozilirovanie kisloĭ alpha-gliukozidazy s tsel'iu napravlennogo transporta ee v lizosomy parenkhimatoznykh kletok pecheni.