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)

beta-Glucosidase activity was measured in control subjects and in five patients with neuropathic Gaucher's disease. In three patients with Gaucher's disease, methylumbelliferyl- and p-nitrophenyl-beta-d-glucopyranoside (4MU- and PNP-beta-glucosidase) activity was almost normal in the liver but markedly reduced in the spleen and fibroblasts. In the other patients with Gaucher's disease 4MU- and PNP-beta-glucosidase activity was also very much reduced in the liver, spleen, and fibroblasts. DEAE-cellulose column chromatography with a chloride gradient elution of the liver extract from a control subject and from two patients with Gaucher's disease, exhibiting normal 4MU- and PNP-beta-glucosidase activity, revealed the presence of two peaks of 4MU- and PNP-beta-glucosidase activity (fractions 1 and 2). pH activity curves of beta-glucosidases and Km measured with 4MU-beta-glucoside in fractions 1 and 2 from patients with Gaucher's liver were identical to those from the control liver. However, fractions 1 and 2 from infantile Gaucher's liver exhibited no activity measured with glucocerebroside whereas those from juvenile Gaucher's liver showed a considerable activity. Glucocerebroside was greatly accumulated in the liver, even though an almost normal activity of 4MU-beta-glucosidase was detected in three of the five patients studied.
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PMID:Neuropathic Gaucher's disease with normal 4-methylumbelliferyl-beta-glucosidase activity in the liver. 87 Aug 71

Lymphoid cell lines (LCL) from 3 adult patients with non-neuropathic Gaucher disease were established by Epstein-Barr virus (EBV) transformation and were investigated from the view of enzymology. Glucosylceramide-beta-glucosidase (GlcCer-beta-glucosidase) was present in soluble and particulate fraction of LCL from normal subjects and was deficient in type 1 Gaucher LCL; the deficiency of all molecular forms, shown by electrofocusing, indicates that they are coded by the same gene. The existence of two non-specific beta-glucosidases, one soluble (minor), the other membrane-bound (major), was demonstrated in leucocytes and LCL from normals; in Gaucher LCL, these were also present in a normal range. Characteristic properties of the non-specific membrane-bound beta-glucosidase were defined: lability at acidic pH and strong inhibitory effect by detergents. These properties allowed to discriminate it from the lysosomal GlcCer-beta-glucosidase and to define optimal assay conditions for determination of residual GlcCer-beta-glucosidase activity in Gaucher disease, using artificial substrate, without interference of non-specific membrane-bound beta-glucosidase. These results demonstrate that EBV-transformed LCL represent an accurate model system for enzymatic studies of Gaucher disease.
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PMID:beta-Glucosidase isoenzymes in Epstein-Barr virus-transformed lymphoid cell lines from normal subjects and patients with type 1 Gaucher disease. 303 13

A 9-year-old girl with juvenile Gaucher disease underwent splenectomy and allogeneic bone marrow transplantation. Her HLA-identical brother with normal cerebroside-beta-glucosidase activity served as donor. One month after transplantation, cerebroside-beta-glucosidase activity in the lymphocytes were normal. Plasma glucosylceramide normalized already after splenectomy and further decreased after marrow transplantation. Glucosylceramide in the erythrocytes was normal around a year after transplantation. The enlarged liver normalized in size by 2 years. Gaucher cells were still present in the bone marrow 1 year after transplantation but had completely disappeared at 3 years. The patient has grown 29 cm during the 5 years that have passed after transplantation compared to 1 cm/year during 3 years before. The patient has a slight obstructive ventilatory impairment, and chest deformities have appeared. Wechsler intelligence scale performance has slowly decreased after transplantation. This may be caused by continued neuronal storage of glucosylceramide. Otherwise, this patient is active and healthy 5 years after bone marrow transplantation.
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PMID:Long-term follow-up of the first successful bone marrow transplantation in Gaucher disease. 313 56

Glucocerebroside beta-glucosidase (glucocerebrosidase) activity was determined from peripheral blood lymphocytes and cultured skin fibroblasts of eight full sibs in a French-Canadian family at risk for Gaucher disease, an autosomal recessive sphingolipidosis resulting from deficient glucocerebrosidase activity. The diagnosis of type 1, non-neuronopathic Gaucher disease was made in all of the five affected sibs on the basis of deficient (7.5 to 15.5% of control mean) glucocerebrosidase activity and absence of neurological involvement. Normal levels of enzyme activity were found in two of the three asymptomatic sibs. The third asymptomatic sib had an intermediate level (about 50% of control mean) of fibroblast and lymphocyte glucocerebrosidase activity, indicating that he is a carrier. Considerable clinical heterogeneity was noted among the five affected sibs. One patient is mildly affected and so far has not developed any orthopaedic complications associated with Gaucher disease. His haematological complications were also reversed after splenectomy 24 years ago. In contrast to this mild presentation, the patient's splenectomised sister has been very anaemic and thrombocytopenic. There have been severe orthopaedic complications associated with Gaucher disease, including vertebral compression, avascular necrosis, and pathological fracture of the long bones. The clinical picture of the other three affected sibs appeared to vary between the two extremes. Although the asymptomatic parents of the patients died many years ago, their heterozygous status with respect to Gaucher disease can be deduced by the presence of Gaucher homozygotes, normal homozygotes, and one heterozygote among their eight offspring. Present findings suggest that the clinical variability of type 1 Gaucher disease may be attributed to variable expressions of the same Gaucher mutant alleles, in addition to the presence of multiple mutant alleles that are widely disseminated in the population.
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PMID:Intrafamilial clinical variability of type 1 Gaucher disease in a French-Canadian family. 338 40

The first part of this review deals the biochemical data concerning human and mammalian beta-glucosidases. Glucosylceramide-beta-glucosidase and non-specific beta-glucosidase are characterized following their physical, functional, structural and genetical properties. The second part deals with the biochemical and pathophysiological data concerning the Gaucher disease.
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PMID:[Beta-glucosidases. Molecular bases of Gaucher's disease]. 393 Oct 39

Glucocerebroside beta-glucosidase (glucocerebrosidase) activity was assayed from cultured fibroblasts of normal individuals, and patients with type 1 (non-neuropathic), type 2 (acute neuropathic), and type 3 (subacute neuropathic) form of Gaucher disease. Residual glucocerebrosidase activity of patients was 8.9 to 17.4% of normal controls, and there was no clear correlation between the level of residual enzyme activity and the different clinical subtypes of the disease. When membrane-bound glucocerebrosidase activity was assayed in the presence of crude brain lipid extracts or purified phosphatidylserine, enzyme from both the normal and type 1 Gaucher fibroblasts was stimulated dramatically (35-60% by crude extracts, 85-90% by phosphatidylserine). This stimulation was not observed with fibroblast glucocerebrosidase of an infantile type 2 and two juvenile type 3 Gaucher patients. The presence of inhibitors of glucocerebrosidase in these type 2 and type 3 Gaucher cells was not detected. Contrary to the mutant enzyme from these Gaucher fibroblasts, glucocerebrosidase from fibroblasts of two adult type 3 Gaucher patients with cerebral involvement was stimulated substantially (72-85%) by phosphatidylserine. When membrane-bound glucocerebrosidase from fibroblasts of the infantile type 2 and juvenile type 3 patients was solubilized with sodium cholate (1% w/v) and delipidated, the phospholipid stimulation of enzyme activity was restored. These findings suggest that considerable clinical and biochemical heterogeneity exists among patients with neuropathic Gaucher disease and that phosphatidylserine activation cannot be used as a reliable indicator in predicting future onset of neurodegeneration in Gaucher patients. The possibility of an aberrant binding of mutant glucocerebrosidase to the lysosomal membrane in juvenile type 3 form of Gaucher disease is discussed.
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PMID:Gaucher disease: the effects of phosphatidylserine on glucocerebrosidase from normal and Gaucher fibroblasts. 643 68

Three distinct forms of beta-glucosidase were separated by Bio-Gel P-150 gel filtration from the 105,000 x g supernatant of liver, placenta and fibroblasts extracted in the presence of Cutscum and sodium taurocholate. Glucosylceramide beta-glucosidase was mostly particulate (more than 80%), had an apparent molecular weight of about 67,000 and exhibited a pH optimum of 5.9 with the natural substrate, glucosylceramide, and a pH optimum of 4.2 with the artificial substrate, 4-methylumbelliferyl beta-D-glucoside. This enzyme form was deficient in tissue specimens from patients with Gaucher disease. A soluble form with neutral pH optimum (6.2) was found to occur in high levels in liver and placenta but was relatively low in skin fibroblasts. This beta-glucosidase form had an apparent molecular weight of about 42,000 and was normal in the Gaucher tissues examined. Another neutral beta-glucosidase was found in the membranous fraction, it had a molecular weight greater than 150,000, cleaved 4-methylumbelliferyl beta-D-glucoside but not glucosylceramide, with an optimum pH of about 5.7. The membranous acidic and neutral forms could not be precipitated by antibodies to the soluble neutral beta-glucosidase. The three enzyme forms differed from one another by their heat inactivation profiles, the soluble neutral form was most labile, the membranous neutral form was most stable, and the acidic form with glucosylceramide beta-glucosidase activity had intermediate thermostability.
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PMID:Soluble and membranous neutral beta-glucosidases. 681 82

Glucosylceramide: beta-glucosidase (glucocerebrosidase, EC 3.2.1.45) has been purified 12 900-fold from human placenta using a specific affinity column. The ligand, glucosyl sphingosine, prepared from glucocerebroside by alkaline hydrolysis, was attached to epoxy-activated Sepharose 6B. The enzyme was applied to the column in citrate--butanol or citrate--ethylene glycol solution at its pH optimum (5.6). No enzyme was bound in the presence of detergent. Glucocerebrosidase was eluted with citrate--taurocholate buffer at low pH or with citrate--taurocholate buffer containing D-gluconolactone at the pH optimum. Citrate--taurocholate solution alone at the pH optimum would not elute the enzyme. The enzyme hydrolyzed both the natural substrate, glucocerebroside, and the artificial substrate, 4-methylumbelliferyl glucopyranoside. Glucocerebrosidase migrated as a single band on 10% sodium dodecyl sulfate--polyacrylamide tube and (or) slab gels, corresponding to a molecular weight of 75 000. It also ran as a single zone of enzyme activity or protein on native gels, composed of 2.2% polyacrylamide--0.4% agarose containing sodium taurocholate. This is the first reported use of this gel system for the examination of glucocerebrosidase. Overall recovery is 30%. The procedure represents a more rapid and specific technique for purification of glucocerebrosidase than those previously reported.
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PMID:Purification of glucosylceramidase by affinity chromatography. 717 89

Glucosylceramide beta-glucosidase is a membrane-bound lysosomal hydrolase that is activated by acidic lipids, the most effective of which is phosphatidylserine (PtdSer), and an activator protein, saposin C. This report documents effects of Ca2+ ions on PtdSer- and saposin C-enhanced beta-glucosidase activity. Ca2+ either increased or decreased enzyme activity, depending on (1) the concentration of phospholipid, and (2) the presence or absence of saposin C. At PtdSer concentrations between 7.6 and 76 microM, in the absence of saposin C, Ca2+ caused an increase in beta-glucosidase activity up to 3 times that measured with PtdSer alone; this was due to both an increase in Vmax, and a decrease in Km. In contrast, at PtdSer concentrations greater than 100 microM, Ca2+ inhibited beta-glucosidase activity by 50%, due to a 2-fold increase in Km. Ca2+ was inhibitory at all PtdSer concentrations tested when both PtdSer and saposin C were present in the assay. Ca2+ ions were also shown to cause changes in the aggregation states of PtdSer. These results suggest that changes in Ca2+ concentration may play a role in regulating beta-glucosidase activity in vivo, thereby modulating sphingolipid metabolism. The implications of these findings are discussed.
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PMID:Effects of calcium on phosphatidylserine- and saposin C-stimulated glucosylceramide beta-glucosidase activity. 765 96

Glucosylceramide (GlcCer) and related glycosphingolipids have been implicated as causal elements in both the growth of cells and in the regulation of hormonal signaling. We therefore studied whether the renal hypertrophy induced by diabetes was associated with enhanced synthesis of glycosphingolipids. 16 d after the induction of diabetes, increases in renal size and concentration of glucocerebroside and ganglioside GM3 were observed paralleling an increase in UDP-Glc concentration. GlcCer synthase and beta-glucosidase-specific activities were no different between control and diabetic kidneys. The apparent Km of the GlcCer synthase with respect to UDP-Glc was 250 microM and was unchanged in the diabetic kidneys. The observed concentrations of UDP-Glc were 149 and 237 microM in control and diabetic kidneys, respectively. The UDP-Glc level is thus rate limiting with regard to GlcCer synthesis. To determine whether the changes in glycolipid content were functionally significant, diabetic and control groups were treated with the GlcCer synthase inhibitor, D-threo-1-phenyl-2-decanoyl-amino-3-morpholino-1- propanol, 2 wk after the induction of diabetes. Kidney weights in the diabetic rats treated with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol were no different than the control groups. Morphometric analysis of glomerular volumes paralleled changes in renal growth. Glycosphingolipid formation may therefore represent a significant pathway for glucose utilization in early diabetic nephropathy.
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PMID:A role for glycosphingolipid accumulation in the renal hypertrophy of streptozotocin-induced diabetes mellitus. 845 61


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