Altered molecular size of N-acetylglucosamine 1-phosphotransferase in I-cell disease and pseudo-Hurler polydystrophy.
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.
Ben-Yoseph
Y
Y
C.S. Mott Center for Human Growth and Development, Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI 48201.
Potier
M
M
Mitchell
D A
DA
Pack
B A
BA
Melançon
S B
SB
Nadler
H L
HL
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)
D010770:Phosphotransferases; D017855:Transferases (Other Substituted Phosphate Groups); C023222:UDPacetylglucosamine-dolichyl-phosphate acetylglucosamine-1-phosphate transferase