title: Altered molecular size of N-acetylglucosamine 1-phosphotransferase in I-cell disease and pseudo-Hurler polydystrophy.
abstract: The size of the mutant N-acetylglucosamine 1-phosphotransferase in Golgi membranes from fibroblasts of patients with I-cell disease and classical pseudo-Hurler polydystrophy, which comprised one complementation group characterized by deficiency towards both artificial and natural acceptor substrates, was significantly smaller than the normal enzyme, 151-174 kDa compared with 225-278 kDa. The size of the mutant enzyme from cell lines of patients with variant forms of pseudo-Hurler polydystrophy, which comprised another complementation group characterized by normal activity towards mono- and oligo-saccharide substrates, was significantly larger than the normal enzyme, ranging from 321 to 356 kDa in two families and from 528 to 547 kDa in a third family. These findings suggest that the mutations in I-cell disease and classical pseudo-Hurler polydystrophy result in a missing enzyme component, which renders the enzyme catalytically inefficient toward any type of acceptor substrate. In contrast, the mutations in the variant forms of pseudo-Hurler polydystrophy produce a larger enzyme molecule which is active toward small substrates but is incapable of binding natural lysosomal glycoprotein substrates.
authors.affiliation: C.S. Mott Center for Human Growth and Development, Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI 48201.
authors.forename: Y
authors.initials: Y
authors.lastname: Ben-Yoseph
authors.forename: M
authors.initials: M
authors.lastname: Potier
authors.forename: D A
authors.initials: DA
authors.lastname: Mitchell
authors.forename: B A
authors.initials: BA
authors.lastname: Pack
authors.forename: S B
authors.initials: SB
authors.lastname: Melançon
authors.forename: H L
authors.initials: HL
authors.lastname: Nadler
mesh_terms: D002460:Cell Line; D006801:Humans; D008970:Molecular Weight; D009081:Mucolipidoses / Q000201:enzymology*; D008059:Mucopolysaccharidosis I / Q000201:enzymology*; D009154:Mutation; D010770:Phosphotransferases / Q000378:metabolism* / Q000528:radiation effects; D017855:Transferases (Other Substituted Phosphate Groups)
chemical_list: D010770:Phosphotransferases; D017855:Transferases (Other Substituted Phosphate Groups); C023222:UDPacetylglucosamine-dolichyl-phosphate acetylglucosamine-1-phosphate transferase