title: Metabolism of GM1 ganglioside in cultured skin fibroblasts: anomalies in gangliosidoses, sialidoses, and sphingolipid activator protein (SAP, saposin) 1 and prosaposin deficient disorders.
abstract: Cultured skin fibroblasts from controls and patients with lysosomal storage diseases were loaded with GM1 ganglioside that had been labelled with tritium in its ceramide moiety. After a 65-h or 240-h incubation, a large percentage of this ganglioside remained undegraded in GM1 gangliosidoses, whereas in the other storage diseases studied, one of its metabolites accumulated by 2-4 fold relative to controls. Labelled GM2 ganglioside accumulated in 4 variants of GM2 gangliosidosis, whereas labelled GM3 ganglioside accumulated in sialidosis, galactosialidoses and sphingolipid activator protein 1 (SAP-1, saposin B) and prosaposin (saposin A, B, C and D) deficient lipidoses. The reduced degradation of GM3 ganglioside in the SAP-1 and prosaposin deficiencies was attributed to the deficient function of SAP-1. The prosaposin deficient cells also showed a reduced re-utilization of radioactive metabolites from GM1 ganglioside (i.e. sphingosine and fatty acid) for phospholipid biosynthesis compared with fibroblasts from the SAP-1 deficient patient or normal controls. This anomaly was ascribed to the previously shown defect in ceramide degradation in prosaposin deficiency.
authors.affiliation: Institut für Hirnforschung Universitaät, Tübingen, Federal Republic of Germany.
authors.forename: B
authors.initials: B
authors.lastname: Schmid
authors.forename: B C
authors.initials: BC
authors.lastname: Paton
authors.forename: K
authors.initials: K
authors.lastname: Sandhoff
authors.forename: K
authors.initials: K
authors.lastname: Harzer
mesh_terms: D002675:Child, Preschool; D002855:Chromatography, Thin Layer; D005347:Fibroblasts / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000378:metabolism*; D005678:G(M2) Ganglioside / Q000378:metabolism; D005679:G(M3) Ganglioside / Q000378:metabolism; D016537:Gangliosidosis, GM1 / Q000378:metabolism; D006023:Glycoproteins / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D007223:Infant; D016464:Lysosomal Storage Diseases / Q000378:metabolism*; D009439:Neuraminidase / Q000172:deficiency; D011498:Protein Precursors / Q000172:deficiency / Q000378:metabolism; D049231:Saposins; D012867:Skin / Q000166:cytology / Q000378:metabolism; D049128:Sphingolipid Activator Proteins; D013106:Sphingolipidoses / Q000378:metabolism
chemical_list: D005679:G(M3) Ganglioside; D006023:Glycoproteins; C483345:PSAP protein, human; D011498:Protein Precursors; D049231:Saposins; D049128:Sphingolipid Activator Proteins; D005678:G(M2) Ganglioside; D005677:G(M1) Ganglioside; D009439:Neuraminidase