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)

Sphingolipidoses in infancy and adulthood and associated metabolic disturbances are caused by a recessively inherited, circumscribed lysosomal enzyme deficiency in the catabolism of various structural tissue substances. After presenting detailed methods for the quantitative assay of activities of lysosomal hydrolytic enzymes in leukocytes, serum , fibroblasts, urine and organ tissue with the aid of synthetic chromogenic and fluorescent substrates the signigicance of these methods for clinical diagnosis, for the detection of homozygote persons before developing clinical symptoms (preclinical diagnosis), for the preventive prenatal diagnosis and forthe detection of heterozygote carriers is described for the following diseases: Deficiency of hexosaminidase A and B, deficiency of beta-glucosidase, deficiency or arylsulfatase A, deficiency of alpha-galactosidase, deficiency of alpha-glucosidase.
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PMID:[Clinical, preclinical and prenatal diagnosis of congenital sphingolipidoses by determining lysosomal hydrolases (author's transl)]. 41 9

We report a new assay for the detection of individuals heterozygous and homozygous for Gaucher's disease which requires relatively small samples of whole blood (0.3 ml), and which determines 4-methylumbelliferyl-beta-D-glucopyranoside:beta-glucosidase activity under conditions optimal for the determination of leukocyte glucocerebroside:beta-glucocereborsidase activity. The procedure involves the preparation of a leukocyte pellet from 50 mul of whole blood by hypotonic lysis of erythrocytes, followed by assay of beta-glucosidase activity at pH 5.5 in the presence of sodium taurocholate (0.6 g/100 ml). The methods described may also prove to be useful for the diagnosis of other diseases of enzyme deficiency which use fluorogenic substrates and leukocytes as a source of enzyme, such as Fabry's disease, Tay-Sachs disease, and generalized gangliosidosis.
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PMID:A microassay for Gaucher's disease. 80 4

A 38-year-old lady, who had a previous infant with type 2 Gaucher disease, underwent prenatal diagnosis by chorionic villus sampling at 9 weeks' gestation. Results on the fresh villus revealed a 47,XY,+21 karyotype and a marked deficiency (2 per cent of control) of beta-glucosidase activity. Following termination, villus material was cultured which initially revealed only a partial enzyme deficiency and a normal female karyotype, i.e., maternal cells. A subsequent culture contained 47,XY,+21 cells which were deficient in beta-glucosidase activity, thus confirming the diagnosis. The results in this interesting case illustrate the potential dangers of maternal cell contamination in cultured villus cells.
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PMID:First trimester diagnosis of Gaucher disease in a fetus with trisomy 21. 297 55

A method is described for the assay of glucosyl ceramide beta-glucosidase (glucocerebrosidase) in white blood cells, cultured fibroblasts and amniotic cells, and in tissue homogenates. Glucosyl ceramide extracted from Gaucher spleen and labelled by catalytically adding tritium to the ceramide double bonds was used as the substrate in the presence of pure sodium cholate as detergent. The specificity of the test was established by demonstrating the enzyme deficiency in 25 cases with Gaucher's disease type 1 and 2. In two prenatal cases quantitative liver lipid analysis showed that glucosyl ceramide storage starts in Gaucher fetuses when they are about 20 weeks old.
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PMID:Enzymic diagnosis in 27 cases with Gaucher's disease. 740 11

Genetically determined enzyme deficiency causing failure of the lysosomal apparatus is called lysosomal disease. In normal cell the activity of lysosomal enzymes exceeds many times the requirements of the cell. In some individuals due to gene mutation the activity of an intracellular enzyme is only slightly higher than in patients with lysosomal disease but much lower than in the general population, although without evident metabolic and clinical consequences. This situation is called enzyme pseudodeficiency. As yet cases have been reported of the pseudodeficiency of beta-galactocerebrosidase, beta-glucoronidase, beta-glucosidase, beta-hexosoaminidase A and arylosulfatase A. The character of the mutation is called in the case of the two last enzymes and a laboratory method is available for differentiation of pseudodeficiency from the actual lysosomal disease. It is not known whether in pseudodeficiency of an enzyme clinical manifestations could appear in older age.
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PMID:[Pseudodeficiency of lysosomal enzymes]. 759 81

The metabolism of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph) was studied using cultured fibroblasts deficient in acid beta-glucosidase activity. In fibroblasts from patients with Gaucher's disease, in vitro beta-glucosidase activities were 2.7-11.7% and 4.8-13.6% of control values when 4-methylumbelliferyl beta-D-glucoside and GlcSph were used as substrates, respectively. In spite of the enzyme deficiency, GlcCer and GlcSph, the natural substrates of the deficient enzyme, did not accumulate in the cells. When normal fibroblasts were incubated with conduritol B epoxide (CBE), a specific inhibitor of acid beta-glucosidase, the in vitro enzyme activities decreased dose-dependently (2.2-2.4% of control values at 50 microM CBE), and GlcCer and GlcSph accumulated in the cells at concentrations of CBE higher than 50 microM. To investigate the intracellular metabolism of GlcCer and GlcSph, either radioactive GlcCer or GlcSph was loaded onto cultured fibroblasts. In fibroblasts treated with a high dose of CBE (1 mM), the degradation of GlcCer and GlcSph was retarded (5-21% on day 7; normal range, 81-99%), while in fibroblasts from patients with Gaucher's disease, both the pattern and rate of the degradation of the lipids (83-97% on day 7) were almost the same as those seen in the control cells. These results indicate that in Gaucher's disease fibroblasts the intracellular metabolism of GlcCer and GlcSph is normal in spite of the deficiency in beta-glucosidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucosylceramide and glucosylsphingosine metabolism in cultured fibroblasts deficient in acid beta-glucosidase activity. 818 16

Although the first description of a lysosomal storage disorder was that of Tay-Sachs disease in 1881, the lysosome was not discovered until 1955, by Christian De Duve. The first demonstration by Hers in 1963 of a link between an enzyme deficiency and a storage disorder (Pompe's disease) paved the way for a series of seminal discoveries about the intracellular biology of these enzymes and their substrates, culminating in the successful treatment of Gaucher's disease with beta-glucosidase in the early 1990s. It is now recognized that these disorders are not simply a consequence of pure storage, but result from perturbation of complex cell signalling mechanisms. These in turn give rise to secondary structural and biochemical changes, which have important implications for therapy. Significant challenges remain, particularly the treatment of central nervous system disease. It is hoped that recent advances in our understanding of lysosomal biology will enable successful therapies to be developed.
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PMID:Lysosomal storage disorders. 1568 51