Brain glucocerebrosidase in Gaucher's disease.
Using glucocerebroside labeled with carbon 14 as the substrate, we determined that homogenates of brain tissue from both neuropathic and nonneuropathic cases of Gaucher's disease were profoundly deficient (more than 85%) in glucocerebrosidase activity. The beta-glucosidase activity, as measured with 4-methylumbelliferyl-beta-D-glucopyranoside as the substrate, in the homogenates of brain from four cases of Gaucher's disease was less sensitive to inhibition by conduritol B epoxide (CBE) when compared with normal brain beta-glucosidase. However, when homogenates were assayed with radiolabeled glucocerebroside as the substrate, no differential sensitivity toward CBE was indicated, suggesting the presence of an additional, CBE-insensitive, beta-glucosidase in brain tissue. Residual glucocerebrosidase activity partially purified from the brain of an adult with type 1 Gaucher's disease was activated threefold by gluconoyl hydrazine, whereas the same enzyme from control brain was unaffected, and eight times less sensitive to gluconolactone inhibition.
D000328:Adult; D001921:Brain / Q000201:enzymology*; D002648:Child; D002675:Child, Preschool; D005776:Gaucher Disease / Q000150:complications / Q000201:enzymology*; D005959:Glucosidases / Q000032:analysis*; D005962:Glucosylceramidase / Q000032:analysis*; D006801:Humans; D007700:Kinetics; D009422:Nervous System Diseases / Q000150:complications; D012016:Reference Values; D001617:beta-Glucosidase / Q000378:metabolism
D005959:Glucosidases; D001617:beta-Glucosidase; D005962:Glucosylceramidase