Properties of beta-glucosidase in cultured skin fibroblasts from controls and patients with Gaucher disease.
Membrane-bound beta-glucosidase from cultured skin fibroblasts can be solubilized in an active form by treatment of membrane preparations with a mixture of Triton X-100 and sodium taurocholate. Several properties of the solubilized enzyme have been studied in fibroblasts from normal, healthy individuals and from 14 patients with different clinical forms of Gaucher disease. The patients studied were classified as follows: group 1 consisted of 10 chronic patients, all (with one exception) of Ashkenazi Jewish origin; group 2 consisted of three black American patients with severe visceral symptoms, manifest from early childhood, but with no apparent neurological involvement; and group 3 consisted of a single white patient with the classical infantile form of the disease. Specific beta-glucosidase activity ranged from 6.6% to 16.5% mean control value in group 1 patients and from 4.1% to 5.8% in groups 2 and 3. When compared with the enzyme from control fibroblasts, the enzyme from chronic Gaucher patients (group 1) was more rapidly inactivated at 50 degrees C, had an altered pH curve, was less effectively inhibited by deoxycorticosterone-beta-glucoside, and was more effectively inhibited by deoxycorticosterone. The enzyme from patients in groups 2 and 3 was qualitatively indistinguishable from the control enzyme in terms of these parameters. No differences in Km (4-methylumbelliferyl-beta-glucoside) or sedimentation coefficient were found between the beta-glucosidases from control and Gaucher cells. The results demonstrate that cells from Ashkenazi Jewish patients with the chronic form of Gaucher disease contain a structurally altered form of beta-glucosidase. This enzyme differs both from normal beta-glucosidase and from the residual enzyme in patients of different ethnic origin and with clinically more severe forms of the disease.
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D002648:Child; D002908:Chronic Disease; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005776:Gaucher Disease / Q000175:diagnosis / Q000201:enzymology*; D005959:Glucosidases / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000201:enzymology; D001617:beta-Glucosidase / Q000378:metabolism*
D005959:Glucosidases; D001617:beta-Glucosidase