Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.21 (beta-glucosidase)
 3,280 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The twitcher mutant mouse, the animal model of Krabbe disease (human globoid cell leukodystrophy), is characterized by apparent deficiency of galactosylceramide beta-galactosidase activity. Saposin A and C, the heat-stable small sphingolipid activator glycoproteins, stimulate the activity of galactosylceramide beta-galactosidase as well as glucosylceramide beta-glucoside. The role of these saposins in the twitcher mutation was investigated. Boiled supernatant fractions, which contained saposins, were prepared from homogenates of twitcher brain, liver, kidney, and spleen. These preparations showed an almost identical effect on the activity of purified glucosylceramide beta-glucosidase (measured by hydrolysis of 4-methylumbelliferyl-beta-glucoside) with similar preparations from control tissues. The effect on the activity of galactosylceramide beta-galactosidase as well as 4-methylumbelliferyl-beta-glucoside beta-glucosidase in the twitcher brain and liver homogenates by authentic saposin A and C was similar to that in control tissues. These results suggest that the twitcher mutation does not affect the concentrations of saposin A or C or their interaction with galactosylceramide beta-galactosidase.
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PMID:Saposins (sphingolipid activator proteins) in the twitcher mutant mouse. 212 Mar 88

Sphingolipidoses are an heterogeneous group of inherited disorders of lipid metabolism affecting primarily the central nervous system. These disorders occur chiefly in the pediatric population, and the degenerative nature of the disease processes is generally characterized by diffuse and progressive involvement of neurones (gray matter) with psychomotor retardation and myoclonus or of fiber tracts (white matter) with weakness and spasticity. Biochemical research has identified the defects in the sphingolipidoses to specific lysosomal enzymes. For example, Niemann-Pick disease lacks sphingomyelinase; Krabbe's disease lacks galactocerebrosidase; Gaucher's disease lacks beta-D-glucosidase; metachromatic leukodystrophy lacks sulfatase; Tay-Sachs disease lacks hexosaminidase A; and generalized gangliosidosis lacks beta-galactosidase. Although there are no currently available modes of rendering corrective therapy in these disorders, a definitive diagnosis is possible both antepartum as well as postpartum. This information provides a sound and accurate basis for genetic counseling.
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PMID:Sphingolipidoses. 555 2

A heat-stable protein was isolated from the spleen of a patient with Gaucher's disease. This protein will activate glucosylceramide beta-glucosidase activity (Ho, M.W. and O'Brien, J.S. (1971) Proc. Natl. Acad. Sci. U.S.A. 68, 2810-2813). When the specificity of this activator was tested using other enzymes and substrates, it was found to activate galactosylceramide beta-galactosidase activity and sphingomyelinase but not GM1 beta-galactosidase or sulfatide sulfatase. The ability to stimulate galactosylceramide beta-galactosidase was optimum at pH 4.6 in the presence of pure phosphatidylserine or other acidic lipids such as sulfatide and phosphatidylinositol. The partially purified activator protein could stimulate galactosylceramide beta-galactosidase activity in brain, liver, leukocytes and cultured fibroblasts. It was not able to stimulate the activity of this enzyme in tissue samples from patients with Krabbe's disease, demonstrating that it was acting on galactosylceramide beta-galactosidase and not GM1 beta-galactosidase. It was slowly denatured by treatment with Pronase, reaching 16% of starting levels after 24 h at 50 degrees C. Attempts to separate the abilities of this activator preparation to stimulate several lysosomal hydrolases by column chromatography were not successful.
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PMID:A protein activator of galactosylceramide beta-galactosidase. 712 30

The aim of this study was to diagnose lipid storage diseases in embryos at the preimplantation stage. Two parallel approaches were employed. Firstly, activities of several sphingolipid hydrolases were determined in extracts of murine embryos and also human oocytes and polyspermic embryos. Sensitive fluorescent or fluorogenic procedures provided indications that Tay-Sachs, Gaucher and Krabbe diseases might be diagnosed in one human blastomere, while for Niemann-Pick disease two might be required. Secondly, pyrene lipids were administered into murine embryos and their fluorescence was quantified by computerized imaging microscopy. As a model of Gaucher disease, the fluorescent substrate pyrene glucosylceramide was administered into murine embryos in the presence or absence of an inhibitor of the enzyme beta-glucosidase. Because of decreased degradation of the substrate in enzyme-inhibited cells, the fluorescence per blastomere was considerably greater relative to those which received no inhibitor. The results indicated that lipid storage diseases might be diagnosed in single human blastomeres at the preimplantation stage, obviating the need for pre-natal diagnosis and abortion of affected foetuses.
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PMID:Diagnosing sphingolipidoses in murine and human embryos. 847 38

This computational study is a summary of structural properties of the beta-glucosidase subfamily B. Computations were carried out using GCG package programs. All sequences used in this analysis were taken from the protein data bank. The multialignment and the phylogenetic tree of the beta-glucosidase sub-family B are shown. The conserved patterns: DGP, GRNFE, DPYL, KHF, SDW, GLD, VLLKN in the N-terminal region and FGYGLSY in the C-terminal part should be pointed out. C-terminal parts of the Butyrivibrio fibrisolvens and Ruminoccocus albus beta-glucosidase sequences can be aligned to the N-terminal region of the other members of the subfamily. A crossed homology model in sub-family B beta-glucosidases is described.
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PMID:A sequence analysis of the beta-glucosidase sub-family B. 854 11

Methylumbelliferyl-tetra-N-acetylchitotetraoside hydrolase activity was increased 53- to 484-fold in plasma from Gaucher disease patients and no activator could be found. High activity was also measured in other lysosomal storage diseases including Krabbe disease, Wolman disease, GM1-gangliosidosis and to a lesser extent Niemann-Pick disease type B, but the activities were lower than the lowest values in Gaucher patients. Kinetic properties of the high activity in Gaucher plasma were similar to those of controls. It is not known whether the increased activity represents intrinsic enzyme activity or increased enzyme concentration. It is possible that this enzyme may help in the detection of Gaucher disease or in the assessment of enzyme therapy with beta-D-glucosidase (Ceredase).
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PMID:Marked increase of methylumbelliferyl-tetra-N-acetylchitotetraoside hydrolase activity in plasma from Gaucher disease patients. 880 78