Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.21 (beta-glucosidase)
3,280 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Electrofocusing allows to separate the beta-glucosidases from normal spleen in several molecular forms: a non specific beta-glucosidase form (pl 4.6) and two forms of beta-glucocerebrosidase (pl 5.0 and pl 6.5). beta-glucosidase and beta-glucocerbrosidase differ with regard to their thermal stability. In a spleen from a patient with non neuronopathis Gaucher's disease (type I or adult form), molecular whereas the non specific beta-glucosidase is not significantly decreased. Thus, the beta-glucocerebrosidase forms and the non specific beta-glucosidase are not coded by the same gene. The separation of molecular forms of beta-glucosidase allows to measure the part of specific beta-glucosidase activity in the assay of beta-glucocerebrosidase by artificial substrate, 4-methylumbeliferyl-beta-D-glucopyranoside.
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PMID:[Separation by electrofocusing of the molecular forms of splenic beta-glucosidase in normal subjects and Gaucher's disease]. 677 20

The physician who diagnoses Gaucher's disease should take advantage of the noninvasive method that analyzes WBCs for residual beta-glucocerebrosidase and beta-glucosidase activities. When this method is carried out in conjunction with the measurement of serum acid phosphatase levels, a bone marrow examination may be unnecessary. With this method, we studied an adult who had mild splenomegaly and abdominal pain. When bone marrow was finally obtained subsequent to diagnosis by the enzymatic analysis, the deposits that are specifically formed in Gaucher's disease were easily demonstrated by electron microscopy. We believe that these methods are more specific for the diagnosis of Gaucher's disease than is the light microscopic finding of bone marrow cells that have abundant and striated cytoplasm.
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PMID:Gaucher's disease. I. Modern enzymatic and anatomic methods of diagnosis. 677 79

Three fluorometric leukocyte beta -glucosidase assays were compared for their ability to diagnose Gaucher's disease and identify carriers of the disorder: the acid beta-glucosidase assay of Beutler and Kuhl [2], a pH 5.5-sodium taurocholate-dependent assay and a new procedure which employs conduritol B epoxide, an active-site specific inhibitor of glucocerebrosidase. All three assays unambiguously identified patients with Gaucher's disease. With regard to identifying carriers the bile salt dependent assay of Peters et al. and the conduritol B epoxide-dependent procedure gave the greatest discrimination between the mean beta-glucosidase values for the control and heterozygote samples when evaluated using Student's t test. The most reliable assay for the identification of the carrier state was the conduritol B epoxide-dependent procedure which can be expected to provide the fewest false negative results when classifying heterozygotes (5%). However, the fact that none of these methods will completely separate control and heterozygote samples indicates that their use in screening programs will result in a significant number of incorrect assignments.
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PMID:An improved fluorometric leukocyte beta-glucosidase assay for Gaucher's disease. 679 54

Electrophoresis of the beta-glucosidase isozymes from various normal human sources revealed that cultured fibroblasts expressed only the acid beta-glucosidase isozyme. Therefore, selected physical and kinetic properties of the residual acid beta-glucosidase activities in fibroblasts from Gaucher Type 1 homozygotes of various ethnic backgrounds were compared. The findings of different specific activities, thermostabilities, apparent Km values, and electrophoretic migrations of the residual activities from the ethnic variants provided the first biochemical evidence of genetic heterogeneity in Type 1 Gaucher disease.
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PMID:Genetic heterogeneity in type I Gaucher disease. 681 84

Inhibitors and activators of acid beta-glucosidase activity were used as probes to characterize the components of the active site of the membrane bound enzyme, acid beta-glucosidase. Three components of the active site were defined: (1) a catalytic site, (2) an aglycon binding site, and (3) a hydrophobic binding site (Fig. 5A). Similar studies on the residual acid beta-glucosidase in homozygotes with Type 1 Ashkenazi Gaucher disease suggested that this enzyme's hydrophobic site was more hydrophilic than that of the normal enzyme. The defect in this membranous enzymopathy could have resulted from a single base substitution in the structural gene leading to the insertion of a more hydrophilic amino acid in the hydrophobic domain of the gene product. Alternatively, a base substitution which altered the conformation of the enzyme could render the hydrophobic site more hydrophilic. The following consequences of such a mutation would be expected. The mutation would not affect substrate binding to the catalytic site, since the formation of the enzyme-substrate complex (ie, the Km) would not be altered. If the HS site became more hydrophilic, its efficiency for removing the product would be reduced, resulting in a lower substrate turnover (ie, a "Vmax mutation"). Consequently, the binding of glucosyl psychosine, taurocholate, and phosphatidyl serine to the hydrophobic site would be less efficient, resulting in a greater alpha Ki value. Finally, the binding of taurocholate to the HS would be reduced, and this lipid's enhancement of acid beta-glucosidase inhibition by OBG also would be decreased. Since these results are based on kinetic data, confirmation of the hypothesis will require the preparation of homogenous beta-glucosidase from normal and Type 1 Ashkenazi Gaucher sources for amino acid sequencing of the peptides containing the catalytic site as well as the other components of the active site. Such peptides might be identified by their ability to bind radiolabeled inhibitors and/or activating compounds.
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PMID:Gaucher disease: a membranous enzymopathy. 681 58

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

During studies of the nutritional utilization of pyridoxine 5'-beta-D-glucoside, a major form of vitamin B6 in plants, we detected two cytosolic beta-glucosidases in jejunal mucosa. As expected, one was broad specificity beta-glucosidase that hydrolyzed aryl beta-D-glycosides but not pyridoxine beta-D-glucoside. We also found a previously unknown enzyme, designated pyridoxine-beta-D-glucoside hydrolase, that efficiently hydrolyzed pyridoxine beta-D-glucoside. These were separated and purified as follows: broad specificity beta-glucosidase 1460-fold and pyridoxine-beta-D-glucoside hydrolase 36,500-fold. Purified pyridoxine-beta-D-glucoside hydrolase did not hydrolyze any of the aryl glycosides tested but did hydrolyze cellobiose and lactose. Pyridoxine-beta-D-glucoside hydrolase exhibited a pH optimum of 5.5 and apparent molecular mass of 130 kDa by SDS-polyacrylamide gel electrophoresis and 160 kDa by nondenaturing gel filtration, in contrast to 60 kDa for native and denatured broad specificity beta-glucosidase. Glucono-delta-lactone was a strong inhibitor of both enzymes. Ionic and nonionic detergents were inhibitory for each enzyme. Conduritol B epoxide, a potent inhibitor of lysosomal acid beta-glucosidase, inhibited pyridoxine-beta-D-glucoside hydrolase but not broad specificity beta-glucosidase, but both were inhibited by the mechanism-based inhibitor 2-deoxy-2-fluoro-beta-D-glucosyl fluoride. Our findings indicate major differences between these two cytosolic beta-glucosidases. Studies addressing the role of vitamin B6 nutrition in regulating the activity and its consequences regarding pyridoxine glucoside bioavailability are in progress.
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PMID:Cytosolic pyridoxine-beta-D-glucoside hydrolase from porcine jejunal mucosa. Purification, properties, and comparison with broad specificity beta-glucosidase. 940 96

Diagnostic difficulties of Gaucher disease, a disorder resulted from a deficient activity of glucocerebrosidase is reported. Gaucher disease was described in the 16 year old male, 5 years after manifestation of the very first symptoms (fracture and osteomyelitis). At the age of 14, the cirrhosis due to viral hepatitis accompanied with splenomegaly was diagnosed. This findings was not associated with the earlier osseous disorders. Histopathologic examination of the removed spleen facilitate the diagnosis. The second case refers to 20 year old female. Clinical symptoms and additional test pointed to malignant neoplasm of thyroid, the reproductive organs or cancer of indistinguishable primary focus with metastases in the liver. Trepanobiopsy of bone marrow had made an accurate diagnosis possible, while determination of beta-glucosidase activity in peripheral white blood cells, chitotriosidase activity, and molecular investigations of gene specific to beta-glucocerebrosidase proved it.
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PMID:[Diagnostic difficulties in Gaucher disease: report of two cases]. 1033 43

Gaucher disease (GD) is the most frequent lysosomal storage disease, caused by mutations in the acid beta-glucosidase gene (GBA). The c.1226A > G (N370S) mutation is associated with non-neuronopathic disease (type 1). However, we have observed some discrepancy between genotype and phenotype in Spanish Gaucher disease patients homozygous for the c.1226A > G mutation. A deletion of 55 bp in the exon 9 GBA gene, corresponding to the deleted portion of the beta-glucosidase pseudogene, has been previously reported as a cause of erroneous assignment of 1226G/1226G homozygous patients when the genotype has been performed by PCR assay. We had originally identified 25 (out of 124) unrelated Gaucher disease patients as being putative homozygotes for the c.1226A > G mutation. By means of a new PCR-based assay, we were able to distinguish between the true homozygous patients and the carriers of the 55-bp deletion in exon 9 of the GBA gene. The 55-bp deletion was detected in 10 out of 25 samples (40%) [7 with the 55-bp deletion, 1 RecTL, 1 RecNciI (both including the deletion) and one rearrangement]. Such a high prevalence in this sample suggests that this allele can be more common than expected among GD patients.
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PMID:High prevalence of the 55-bp deletion (c.1263del55) in exon 9 of the glucocerebrosidase gene causing misdiagnosis (for homozygous N370S (c.1226A > G) mutation) in Spanish Gaucher disease patients. 1248 1

Gaucher disease, the most prevalent lysosomal storage disease, is characterised by a significant phenotypic variation caused by more than 150 mutations. In order to verify pathogenicity of mutations found in the Czech Gaucher population, the vaccinia expression system was used. The wild-type human beta-glucocerebrosidase cDNA and cDNAs carrying the mutations 72delC, 1326insT, 1263del55, S196P, N370S, L444P, G202E, D409H, T369M, L444P+V460V, and D409H+T369M were expressed in Gaucher fibroblast cell line (L444P/S107L), BSC40, and HeLa G cells. The enzymatic activity and immunological reactivity were analysed. Only beta-glucocerebrosidase-deficient fibroblasts were suitable for expression using plasmid transfection. The expressed beta-glucosidase activity of mutant glucocerebrosidases was in good correlation with the presumed severity of the mutations.
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PMID:Transient expression of wild-type and mutant glucocerebrosidases in hybrid vaccinia expression system. 1273 41


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