title: Activity of glucocerebrosidase in extracts of different cell types from type 1 Gaucher disease patients.
abstract: Glucocerebrosidase activity in extracts of leukocytes, Epstein-Barr virus transformed lymphocytes and fibroblasts from Portuguese Type 1 Gaucher disease patients was studied. The residual glucocerebrosidase activity in all extracts from patients was less than 25% if measured in the presence of bile salt taurocholate. However, if measured in the absence of bile salt the residual enzyme activity in extracts from patients was cell type specific: it was severely reduced in the case of fibroblasts, mildly reduced in the case of lymphoblasts and not significantly reduced in the case of leukocytes. The glucocerebrosidase activity in extracts from all control cell types was stimulated by taurocholate. In the patients the enzyme activity in fibroblasts extracts was also stimulated but that in lymphoblasts and leukocytes was inhibited by the bile salt. The differences in glucocerebrosidase activity (in the absence of taurocholate) in extracts from different cell types from Gaucher disease patients are attributable to differences in the proportion of glucocerebrosidase present as a monomer with low activity (form I) and as a highly active aggregate (form II) that may also contain sphingolipid activator protein 2 (SAP-2). In extracts from leukocytes and lymphocytes from Type 1 Gaucher disease patients, but not in those from fibroblasts, a relatively high proportion of enzyme is present in aggregated form with near normal specific activity.
authors.affiliation: Instituto Genetica Medica Jacinto de Magalhaes, Porto, Portugal.
authors.forename: M C
authors.initials: MC
authors.lastname: Sa Miranda
authors.forename: J M
authors.initials: JM
authors.lastname: Aerts
authors.forename: R
authors.initials: R
authors.lastname: Pinto
authors.forename: A
authors.initials: A
authors.lastname: Fontes
authors.forename: L W
authors.initials: LW
authors.lastname: de Lacerda
authors.forename: S
authors.initials: S
authors.lastname: van Weely
authors.forename: J
authors.initials: J
authors.lastname: Barranger
authors.forename: J M
authors.initials: JM
authors.lastname: Tager
mesh_terms: D002461:Cell Line, Transformed; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000201:enzymology; D005776:Gaucher Disease / Q000201:enzymology* / Q000235:genetics; D005962:Glucosylceramidase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000201:enzymology; D013656:Taurocholic Acid / Q000494:pharmacology
chemical_list: D013656:Taurocholic Acid; D005962:Glucosylceramidase