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Defects in degradation of blood group A and B glycosphingolipids in Schindler and Fabry diseases
- Source :
- Journal of Lipid Research, 43, 1096-1104. American Society for Biochemistry and Molecular Biology Inc., Journal of Lipid Research, 43, 1096-1104, Journal of Lipid Research, 43, 7, pp. 1096-1104, Journal of Lipid Research, Vol 43, Iss 7, Pp 1096-1104 (2002)
- Publication Year :
- 2002
-
Abstract
- Contains fulltext : 185298.pdf (Publisher’s version ) (Open Access) Skin fibroblast cultures from patients with inherited lysosomal enzymopathies, alpha-N-acetylgalactosaminidase (alpha-NAGA) and alpha-galactosidase A deficiencies (Schindler and Fabry disease, respectively), and from normal controls were used to study in situ degradation of blood group A and B glycosphingolipids. Glycosphingolipids A-6-2 (GalNAc (alpha 1-->3)[Fuc alpha 1-->2]Gal(beta1-->4)GlcNAc(beta 1-->3)Gal(beta 1--> 4)Glc (beta 1-->1')Cer, IV(2)-alpha-fucosyl-IV(3)-alpha-N-acetylgalactosaminylneolactotetraosylcer amide), B-6-2 (Gal(alpha 1-->3)[Fuc alpha 1--> 2] Gal (beta 1-->4)GlcNAc(beta 1-->3)Gal(beta 1-->4)Glc(beta 1-->1')Cer, IV(2)- alpha-fucosyl-IV(3)-alpha-galactosylneolactotetraosylceramide), and globoside (GalNAc(beta 1-->3)Gal(alpha 1-->4)Gal(beta 1-->4)Glc(beta 1-->1') Cer, globotetraosylceramide) were tritium labeled in their ceramide moiety and used as natural substrates. The degradation rate of glycolipid A-6-2 was very low in fibroblasts of all the alpha-NAGA-deficient patients (less than 7% of controls), despite very heterogeneous clinical pictures, ruling out different residual enzyme activities as an explanation for the clinical heterogeneity. Strongly elevated urinary excretion of blood group A glycolipids was detected in one patient with blood group A, secretor status (five times higher than upper limit of controls), in support of the notion that blood group A-active glycolipids may contribute as storage compounds in blood group A patients. When glycolipid B-6-2 was fed to alpha-galactosidase A-deficient cells, the degradation rate was surprisingly high (50% of controls), while that of globotriaosylceramide was reduced to less than 15% of control average, presumably reflecting differences in the lysosomal enzymology of polar glycolipids versus less-polar ones. Relatively high-degree degradation of substrates with alpha-D-Galactosyl moieties hints at a possible contribution of other enzymes.
- Subjects :
- Adult
Ceramide
Adolescent
blood group glycolipids
Globotriaosylceramide
Alpha (ethology)
QD415-436
Inborn errors of metabolism
Biochemistry
Glycosphingolipids
ABO Blood-Group System
Cell Line
alpha-N-Acetylgalactosaminidase
chemistry.chemical_compound
Endocrinology
Glycolipid
medicine
Humans
Erfelijke stofwisselingsziekten
Child
Beta (finance)
Skin
chemistry.chemical_classification
Globoside
Neuromusculaire en neurometabole aandoeningen
Chemistry
Cell Biology
in situ metabolism
Fibroblasts
medicine.disease
skin fibroblasts
lysosome targeting
Molecular biology
Fabry disease
carbohydrates (lipids)
Hexosaminidases
Enzyme
Neuromuscular and neurometabolic disorders
Child, Preschool
α-galactosidase A deficiency
Fabry Disease
lipids (amino acids, peptides, and proteins)
α-N-acetylgalactosaminidase deficiency
Subjects
Details
- ISSN :
- 00222275
- Volume :
- 43
- Database :
- OpenAIRE
- Journal :
- Journal of Lipid Research
- Accession number :
- edsair.doi.dedup.....4cd1f5a5f1b53d9c6981a7e99948228b