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

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

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

Lysosomal storage disease is one of the inborn errors of metabolism caused by a deficiency of lysosomal acid hydrolase activity. We describe here the details of screening methods for the diagnosis of this disorder. It is definitely important to perform both enzyme assay of acid hydrolases and the detection of accumulated materials in patient's tissues. Leukocytes (lymphocytes), serum or plasma, and cultured skin fibroblasts are commonly used as the enzyme source for the assay. Although most lysosomal storage diseases can be diagnosed using leukocytes as the enzyme source, enzymatic activities of beta-glucosidase and sialidase in leukocytes are sometimes normal even in patients. At present, the most reliable enzyme source is considered to be cultured skin fibroblasts. Nevertheless, we should remind that we cannot detect a deficiency of galactocerebroside beta-galactosidase activity even using fibroblasts, if we use synthetic substrate. Natural substrates should be employed for the correct diagnosis and for the study of the nature of patient's enzyme. Deficiency of the enzymatic activity in patients should be confirmed by the demonstration of accumulated materials due to the enzyme defect in patient's tissues and urine. The accumulation of mucopolysaccharides and oligosaccharides in urine is obvious in patients with mucopolysaccharidoses and mucolipidoses, respectively. In case of sphingolipidoses, rectal biopsy specimen and blood could be a target of the investigation. In final, the choice of these screening methods should be made solely based on the detailed clinical manifestation of patients.
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PMID:[Screening methods for the diagnosis of lysosomal storage disease]. 857 38

An infant presented with multifocal myoclonus and cyanotic hypoxemia immediately after birth, and severe feeding problems, a protein-losing enteropathy, massive ascites and grand-mal epilepsy marked his rapid downhill course, with death at 17 weeks. At 2 weeks, brain MRI revealed grey matter heterotopias in the parieto-occipital regions suggestive of a cortical morphogenetic disorder. In cultured skin fibroblasts, lipid storage and reduced activities of ceramidase, galactosylceramide beta-galactosidase and glucosylceramide beta-glucosidase were evident. Autopsy disclosed generalised lysosomal lipid storage with macrophages and adrenal cortex prominently affected. The pattern of stored lipids in cultured fibroblasts and in dewaxed spleen tissue blocks was compatible with a diagnosis of prosaposin (pSap) deficiency (pSap-d). Neuropathologically, there was a pronounced generalised neurolysosomal storage combined with a severe depletion of cortical neurons and extreme paucity of myelin and oligodendroglia. This pathology, in particular the massive neuronal loss, differed from that in other neurolipidoses and could be explained by the reduced hydrolysis of multiple sphingolipids and the loss of pSap's neurotrophic function. The absence of immunostainable saposins on tissue sections and the presence of a homozygous c.1 A > T mutation in the prosaposin gene confirmed the diagnosis. PSap-d may be an underdiagnosed condition in infants with severe neurological and dystrophic signs starting immediately after birth.
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PMID:Prosaposin deficiency -- a rarely diagnosed, rapidly progressing, neonatal neurovisceral lipid storage disease. Report of a further patient. 1594 2