Disease relevance of GBA3

• Mutations in the gene encoding cytosolic beta-glucosidase in Gaucher disease [1].
• Experimental patients practiced an algorithm for adjustment of insulin dosage based on daily prebreakfast capillary blood glucose (CBG) measurements and any symptomatic hypoglycemia [2].
• To estimate the frequency of an early-morning glucose rise (EMR) in relatively unselected children with insulin-dependent diabetes mellitus (IDDM), we assessed capillary blood glucose (CBG) at midsleep (0200-0430) and prebreakfast (0700-0800) in 97 children with diabetes at camp [3].
• We conclude that serum CBG is elevated before transmural intestinal injury in this model and may have utility as an early marker of ischemia in patients at risk for NEC [4].
• Serum cytosolic beta-glucosidase activity in a rat model of necrotizing enterocolitis [4].

High impact information on GBA3

• Beta-Glucosides of pyridoxine (a) are prevalent in plant-derived foods, (b) contribute to human nutrition as partially available sources of vitamin B6, (c) undergo partial hydrolysis by a novel mammalian cytosolic beta-glucosidase, and (d) exert a weak antagonistic effect on the utilization of free pyridoxine [5].
• No significant differences in the degree of metabolic control achieved, as measured by mean fasting, preprandial, and postprandial capillary blood glucose (CBG), M values, glycosylated hemoglobin A1 concentration, cholesterol and triglyceride levels were seen between MSI and CSII in the sixteen patients who completed the study [6].
• Taken together with the three-dimensional model, these mutation studies identified the amino-acid residues in the aglycone-binding subsite of hCBG that are essential for flavonoid glucoside binding and catalysis [7].
• Human cytosolic beta-glucosidase (hCBG) is a xenobiotic-metabolizing enzyme that hydrolyses certain flavonoid glucosides, with specificity depending on the aglycone moiety, the type of sugar and the linkage between them [7].
• Based on the substrate specificity of the human enzymes, sequence alignment of family 1 enzymes and analysis of the hCBG structural model, we selected and mutated putative substrate (aglycone) binding site residues [7].

Chemical compound and disease context of GBA3

• Diabetic keto-acidosis (DKA) requires prompt diagnosis and all patients arriving emergency with dehydration, shock, coma, severe respiratory difficulty and evidence of any major illness should be tested for capillary blood glucose (CBG) and urinary ketones urgently not to miss DKA [8].

Biological context of GBA3

• Sequence analysis of the gene encoding cytosolic beta-glucosidase (GBA3) from 4 chromosomes revealed the presence of 4 single-nucleotide substitutions: c.316 G -->A (D106N), c.1353A-->G (Y451Y), c.1368T-->A (Y456X), and c.1540 to 1541AG -->T in the 3' untranslated region [1].
• A full-length CBG cDNA (cbg-1) was cloned from a human liver cDNA library and expressed in the methylotrophic yeast Pichia pastoris at a secretion yield of approximately 10 mg x L-1 [9].
• The implications of the presence of highly non-polar domains in the active site of the cytosolic beta-glucosidase are discussed with regard to its potential physiological substrates [10].
• Genomic sequence analysis suggested that cbgl is encoded by 30 exons [11].
• Analysis of a 2.4-kb cDNA of the cellulose-binding extracellular beta-glucosidase (CBGL) from Phanerochaete chrysosporium suggested that CBGL is organized into two domains, an N-terminal cellulose-binding domain and a C-terminal catalytic domain [11].

Anatomical context of GBA3

• By Northern blot analysis cBGL1 mRNA was expressed most abundantly in the liver, followed by the small intestine, colon, spleen, and kidney [12].
• The serum concentration of cytosolic beta-glucosidase (CBG), an enzyme found primarily in enterocytes, is markedly elevated in animal models of ischemia and bowel obstruction [4].
• This information was used to design an assay system that would allow us to estimate glucocerebrosidase and cytosolic beta-glucosidase activities in extracts of human leukocytes [13].
• Both CBG and the cyanoglucosides occur within the plant cell wall where they are found in separate compartments and only come into contact when the leaf tissue experiences mechanical damage [14].

Associations of GBA3 with chemical compounds

• Cytosolic beta-glucosidase (EC 3.2.1.21) from mammalian liver is a member of the family 1 glycoside hydrolases and is known for its ability to hydrolyse a range of beta-D-glycosides, including beta-D-glucoside and beta-D-galactoside [15].
• The recombinant CBG (reCBG) was purified from the supernatant using a single chromatography step and was shown to be similar to the native enzyme isolated from human liver in terms of physical properties and specific activity towards 4-nitrophenyl-beta-D-glucoside [9].
• In addition, the second-generation fructosamine assay results demonstrated a significant decrease at each week of study, as did the average CBG [16].
• The implications of galactosylsphingosine inhibition of cytosolic beta-glucosidase and the possible role of the enzyme in glycosphingolipid metabolism are discussed [17].
• Figure Stereoscopic view of the ribbon diagram of hCBG complexed with cortisol [18].

Other interactions of GBA3

• Unlike klotho protein, it possesses neither a signal sequence nor a transmembrane domain, suggesting that it is a cytosolic protein, and thus was termed cytosolic beta-glucosidase-like protein-1 (cBGL1) [12].

Analytical, diagnostic and therapeutic context of GBA3

• Testing all with OGTT was the most effective strategy, but the CBG test and risk assessment questionnaire were the most efficient [19].
• Histopathologic injury was categorized as either no or minimal injury or mural necrosis by two masked investigators and CBG activity was measured by ELISA [4].
• OBJECTIVES: To develop an algorithm to standardize capillary blood glucose (CBG) testing in nursing home and rehabilitation patients [20].
• In addition, the observation that the broad-specificity, cytosolic beta-glucosidase was inhibited by hydrophobic glycosphingolipids prompted the definition of a revised purification procedure which took advantage of hydrophobic affinity chromatography [17].
• Expression, purification, characterization and crystallization of a recombinant human cytosolic beta-glucosidase produced in insect cells [21].

References