A genetic defect in the biosynthesis of dermatan sulfate proteoglycan: galactosyltransferase I deficiency in fibroblasts from a patient with a progeroid syndrome.
A small proteoglycan that contains only a single dermatan sulfate chain is the main proteoglycan synthesized by skin fibroblasts. Fibroblasts from a patient with progeroidal appearance and symptoms of the Ehlers-Danlos syndrome have a reduced ability of converting the core protein of this proteoglycan into a mature glycosaminoglycan chain-bearing species. This abnormality is the consequence of a deficiency in galactosyltransferase I (xylosylprotein 4-beta-galactosyltransferase; EC 2.4.1.133), which catalyzes the second glycosyl transfer reaction in the assembly of the dermatan sulfate chain. The glycosaminoglycan-free core protein secreted by the patient's fibroblasts bears an unsubstituted xylose residue. The mutant enzyme is abnormally thermolabile. Preincubation of fibroblasts at 41 degrees C leads to a further reduction in the production of mature proteoglycan and affects the capacity for glycosaminoglycan synthesis on p-nitrophenyl beta-D-xyloside more strongly in the mutant than in control cells.
Quentin
E
E
Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Federal Republic of Germany.
Gladen
A
A
Rodén
L
L
Kresse
H
H
D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D002807:Chondroitin / Q000031:analogs & derivatives*; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis*; D003871:Dermatan Sulfate / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005700:Galactosyltransferases / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D011371:Progeria / Q000201:enzymology / Q000235:genetics*; D011509:Proteoglycans / Q000096:biosynthesis*; D012016:Reference Values; D012867:Skin / Q000201:enzymology; D013696:Temperature; D014994:Xylose / Q000032:analysis
D011508:Chondroitin Sulfate Proteoglycans; D011509:Proteoglycans; C032649:dermatan sulfate proteoglycan; D003871:Dermatan Sulfate; D002807:Chondroitin; D014994:Xylose; D005700:Galactosyltransferases; C063053:xylosylprotein 4-beta-galactosyltransferase; C063054:galactosylxylosylprotein 3-beta-galactosyltransferase