title: Studies on sphingomyelinase and beta-glucosidase activities in Niemann-Pick disease variants. Phosphodiesterase activities measured with natural and artificial substrates.
abstract: Cultured fibroblasts were studied from 12 cases of Niemann-Pick disease group C. In 11, sphingomyelinase and glucocerebrosidase (and beta-glucosidase) activities were reduced to around 50% of those of controls. On isoelectric focusing, all 12 strains lacked sphingomyelinase activity in the major cathodic region (pI 8.0). The defect was also demonstrated with the artificial phosphodiester substrates bis(4-methylumbelliferyl) phosphate and 4-methylumbelliferyl pyrophosphate diester. In control fibroblasts and those heterozygous for types A or B or group C Niemann-Pick disease, the major sphingomyelinase peak electrofocused at pI 8.0. No direct interaction could be demonstrated by mixing experiments between group C Niemann-Pick extracts and those of type A disease or Gaucher disease. Profiles for beta-glucosidase activity appeared normal in Niemann-Pick group C fibroblasts. No reduction of sphingomyelinase or glucocerebrosidase activities was found in Niemann-Pick group C liver, nor any attenuation of cathodic sphingomyelinase activity in the affected tissue. Results suggest that sphingomyelinase expression differs in fibroblasts and liver. Enzyme defects associated with Niemann-Pick disease group C were only observed in cultured cells.
mesh_terms: D005347:Fibroblasts / Q000201:enzymology; D005959:Glucosidases / Q000302:isolation & purification*; D006801:Humans; D007525:Isoelectric Focusing; D008099:Liver / Q000201:enzymology; D009542:Niemann-Pick Diseases / Q000201:enzymology*; D010727:Phosphoric Diester Hydrolases / Q000302:isolation & purification*; D013108:Sphingomyelin Phosphodiesterase / Q000302:isolation & purification*; D013379:Substrate Specificity; D001617:beta-Glucosidase / Q000302:isolation & purification*
chemical_list: D010727:Phosphoric Diester Hydrolases; D013108:Sphingomyelin Phosphodiesterase; D005959:Glucosidases; D001617:beta-Glucosidase