title: Deficiencies of glucosamine-6-sulfate or galactosamine-6-sulfate sulfatases are responsible for different mucopolysaccharidoses.
abstract: [1-3H]Galactitol-6-sulfate, N- [1-3H]acetylgalactosaminitol-6-sulfate, N-[1-3H]acetylglucosaminitol-6-sulfate, N-acetylglucosamine-6-sulfate, and 6-sulfated tetrasaccharides from chondroitin-6-sulfate have been used for the measurement of 6-sulfatase activity of extracts of normal skin fibroblasts and of fibroblasts cultured from patients with genetic mucopolysaccharidoses. With these substrates, extracts of fibroblasts derived from Morquio patients lack or have greatly reduced activities for galactitol-6-sulfate, N-acetylgalactosaminitol-6-sulfate, and 6-sulfated tetrasaccharides but have normal activity for N-acetylglucosamine-6-sulfate and its alditol; those derived from a patient with a newly discovered mucopolysaccharidosis have greatly reduced activity for N-acetylglucosamine-6-sulfate and its alditol but normal activity for galactitol-6-sulfate, N-acetylgalactosaminitol-6-sulfate, and the 6-sulfated tetrasaccharides. These findings demonstrate the existence of two different hexosamine-6-sulfate sulfatases, specific for the glucose or galactose configuration of their substrates. Their respective deficiencies, causing inability to degrade keratan sulfate and heparan sulfate in one case and keratan sulfate and chondroitin-6-sulfate in the other, are responsible for different clinical phenotypes.
authors.affiliation: Laboratories of Connective Tissue Research, Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: N
authors.initials: N
authors.lastname: Di Ferrante
authors.forename: L C
authors.initials: LC
authors.lastname: Ginsberg
authors.forename: P V
authors.initials: PV
authors.lastname: Donnelly
authors.forename: D T
authors.initials: DT
authors.lastname: Di Ferrante
authors.forename: C T
authors.initials: CT
authors.lastname: Caskey
mesh_terms: D000116:Acetylgalactosamine / Q000031:analogs & derivatives / Q000378:metabolism; D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000378:metabolism; D002478:Cells, Cultured; D002675:Child, Preschool; D002809:Chondroitin Sulfates / Q000378:metabolism; D002811:Chondroitinsulfatases / Q000172:deficiency* / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology; D004376:Galactitol / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007632:Keratan Sulfate / Q000378:metabolism; D008297:Male; D009083:Mucopolysaccharidoses / Q000201:enzymology*; D009084:Mucopolysaccharidosis III / Q000201:enzymology; D009085:Mucopolysaccharidosis IV / Q000201:enzymology*; D012867:Skin / Q000166:cytology / Q000201:enzymology; D013379:Substrate Specificity; D013429:Sulfatases / Q000172:deficiency* / Q000378:metabolism
chemical_list: D000116:Acetylgalactosamine; D000117:Acetylglucosamine; D002809:Chondroitin Sulfates; D002811:Chondroitinsulfatases; D004376:Galactitol; D006497:Heparan Sulfate; D007632:Keratan Sulfate; D013429:Sulfatases; C033137:N-acetylglucosamine-6-sulfate; C011631:N-acetylgalactosaminitol; C033828:N-acetylglucosaminitol; C018719:N-acetylglucosamine-6-sulfatase; C102295:GALNS protein, human