Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.20 (alpha-glucosidase)
 4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brush border membrane bound disaccharidases (sucrase and maltase) and lysosomal enzyme (alpha-glucosidase, beta-D-fucosidase and N-acetyl-beta-glucosaminidase) activities awere studied in amniotic fluid (AF). The above enzymes except N-acetyl-beta-glucosaminidase showed a decrease in activity with gestational age beginning at about the 19th week. The activities of sucrase and maltase correlate with the morphological maturation of fetal intestinal mucosa. The distribution of disaccharidases and lysosomal alpha-glucosidase in AF and intestinal mucosa showed different patterns suggesting that these enzymes originate in diverse fetal tissues.
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PMID:Disaccharidase and lysosomal enzyme activities in amniotic fluid, intestinal mucosa and meconium. Correlation between morphology and disaccharidase activities in human fetal small intestine. 34 69

The substrate analogue conduritol B epoxide (CBE) is demonstrated to be an active site-directed inhibitor of human lysosomal alpha-glucosidase. A competitive mode of inhibition is obtained with glycogen as natural and 4-methylumbelliferyl-alpha-D-glucopyranoside as artificial substrate. The inactivation of the enzyme is time and concentration dependent and results in the covalent binding of CBE. Catalytic activity is required for binding to occur. CBE-labeled peptides containing the catalytic residue of lysosomal alpha-glucosidase were isolated and identified by microsequencing and amino acid analysis. The peptides appeared to originate from a protein domain which is highly conserved among alpha-amylases, maltase, glucoamylases, and transglucanosylases. Based on the sequence similarity and the mechanism of CBE binding, Asp-518 is predicted to be the essential carboxylate in the active site of lysosomal alpha-glucosidase. The functional importance of Asp-518 and other residues around the catalytic site was studied by expression of in vitro mutagenized alpha-glucosidase cDNA in transiently transfected COS cells. Substitution of Asp-513 by Glu-513 is shown to interfere with the posttranslational modification and the intracellular transport of the alpha-glucosidase precursor. The residues Trp-516 and Asp-518 are demonstrated to be critical for catalytic function.
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PMID:Human lysosomal alpha-glucosidase. Characterization of the catalytic site. 185 89

Glycogen can be degraded in mammalian tissues by one of three isozymes of glycogen phosphorylase, termed muscle (M), liver (L) and brain (B) after the tissues in which they are preferentially expressed in adult animals, or by members of the family of alpha-glucosidases. In the current study, we have examined the developmental expression of these enzymes and their respective mRNAs in rabbit tissues, with particular emphasis on the developing lung, a tissue in which glycogen serves as an important source of carbon for surfactant phospholipid biosynthesis. Native gel activity assays and RNA blot hybridization analysis revealed that the B isoform of glycogen phosphorylase predominates in fetal and adult lung tissues, accompanied by a low level of expression of the M isoform. Total B and M phosphorylase activities increased during fetal lung development, with a peak at day 28 of gestation, then decreased to the adult level at term. This peak in activity coincided with the peak period of glycogen degradation in developing lung. While the increase in M isozyme activity was correlated with an increase in the level of its mRNA, B isoform mRNA showed no significant alteration during development, suggesting that the increase in B isoform activity is determined by a posttranscriptional mechanism. Analysis of phosphorylase mRNA levels in developing liver, skeletal muscle, brain and heart revealed a diverse expression pattern. The L isozyme mRNA was predominant at all time points in liver, the M isozyme was predominant at all time points in muscle, the B isozyme was predominant at all time points in brain, and heart contained a mixture of B and M mRNA in roughly equal ratios at all time points. Thus, our studies of phosphorylase mRNA in the rabbit provide no evidence for general predominance of the B isozyme in fetal tissues, or for isozyme 'switching' from the B to the L or M forms during development, as has been suggested by others. In addition to the increase in phosphorylase activity, acid, but not neutral alpha-glucosidase activity was found to increase significantly during fetal lung development, again with a peak at day 28 of gestation. Interestingly, RNA blot hybridization analysis with a probe for lysosomal alpha-glucosidase revealed no change in the level of expression of its 4 kb transcript in developing lung. Instead, we observed induction of a structurally related mRNA of 7.4 kb that peaked at day 28 of gestation. Hybridization with a sucrase/isomaltase-specific oligonucleotide excluded the possibility that the 7.4 kb transcript encodes this protein.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Developmental expression of glycogenolytic enzymes in rabbit tissues: possible relationship to fetal lung maturation. 195 55

Rats trained on a diurnal controlled meal-feeding schedule and injected with a single dose of 3,5,3'-triiodothyronine (T3) failed to accumulate liver glycogen and incorporated less D-[6-3H]glucose into glycogen than normally observed during the feeding period. In the experimental group, the concentration of liver adenosine 3',5'-cyclic monophosphate (cAMP) did not fall during feeding and the pattern of activities of glycogen phosphorylase, glycogen synthase, and phosphorylase kinase remained conductive to glycogenolysis. Liver lysosomal alpha-glucosidase activity normally fell during feeding periods. After T3 treatment the activities of alpha-glucosidase and two lysosomal cathepsins (B1 and D) were elevated. The evidence suggests that T3 may induce both liver phosphorylase kinase and lysosomal alpha-glucosidase. This outcome of T3 excess, in concert with previously described T3-inducible systems, provides a plausible explanation for the failure of glycogen accumulation in this experimental model.
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PMID:Mechanisms underlying enhanced glycogenolysis in livers of 3,5,3'-triiodothyronine-treated rats. 210 55

Pompe's disease is characterised by an absence of lysosomal alpha-glucosidase, but this enzyme is also inhibited by Castanospermum australe seeds. Four calves were fed C. australe seeds at the rate of 0.15 g/kg body weight for periods from 1 to 4 days. Lymphocyte alpha-glucosidase activity was reduced by at least 90%, with the majority of inhibition occurring within 8 h of dosing. Several weeks elapsed before activity returned to normal. Significant inhibition of muscle alpha-glucosidase occurred and the ratio of plasma alpha-glucosidase activity measured at pH 5.6 relative to that at pH 3.7 was depressed. In an attempt to induce Pompe's disease, 2 calves were dosed with 1.2 g C. australe seed/kg body weight/day for 13 months. Lymphocyte and muscle alpha-glucosidase activities were markedly reduced over the entire period of feeding, but the animals showed no clinical signs of disease. Tissue cells were not vacuolated nor did they show any apparent accumulation of glycogen. Despite significant inhibition of alpha-glucosidase in skeletal and cardiac muscle, liver, kidney and brain, it is suggested that there was sufficient residual enzyme to prevent induction of a phenocopy of Pompe's disease.
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PMID:Inhibition of alpha-glucosidase in cattle by Castanospermum australe: an attempted phenocopy of Pompe's disease. 265 94

The lysosomal storage disorder glycogenosis type II, caused by a deficiency of lysosomal alpha-glucosidase, is very heterogeneous in its clinical presentation. It has been suggested that this heterogeneity may be due to differential expression of neutral alpha-glucosidases. We have therefore analysed the activity of the major neutral alpha-glucosidases in cultured fibroblasts or muscle cells from 26 patients with glycogenosis type II. The results indicate that there is no correlation between the expression of neutral alpha-glucosidase isoenzymes and the clinical phenotype of this disease.
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PMID:An investigation of the possible influence of neutral alpha-glucosidases on the clinical heterogeneity of glycogenosis type II. 268 40

We have shown previously (R.P.J. Oude Elferink, E.M. Brouwer-Kelder, I. Surya, A. Strijland, M. Kroos, A.J.J. Reuser, J.M. Tager, Eur. J. Biochem. 139, 489-495 (1984)) that human urine contains considerable amounts of a precursor form of lysosomal alpha-glucosidase (about 50% of the total alpha-glucosidase activity present). We have now purified alpha-glucosidase from human kidney. Only about 5 to 10% of the total lysosomal alpha-glucosidase present in kidney comprises the precursor form of the enzyme. By means of immunocytochemistry using monoclonal antibodies, the precursor of alpha-glucosidase was detected in the brush border of the proximal tubule cells. Taking into account the amount of precursor alpha-glucosidase excreted daily into the urine and the amount present in the kidneys, we conclude that extensive secretion of precursor alpha-glucosidase occurs from the brush border of the proximal tubules.
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PMID:Secretion of a precursor form of lysosomal alpha-glucosidase from the brush border of human kidney proximal tubule cells. 269 57

Chemical galactosylation of human liver tissue lysosomal alpha-glucosidase was carried out. As a result of the modification some physicochemical properties of the enzyme were altered, while its stability and catalytic activity were maintained. An ability of the galactosylated alpha-glucosidase to interact with asialoglycoprotein receptor from mice liver tissue was studied in vitro. The reaction required Ca2+. A specific inhibitor of the receptor, N-acetyl galactosamine, as well as high concentrations of native glycoproteins and neoglycoproteins containing terminal galactose inhibited the receptor binding of the 125I-galactosylated alpha-glucosidase. Native alpha-glucosidase was not bound with the receptor. Antireceptor antibodies inhibited similarly binding of both native ligand, asialoorosomucoid and the galactosylated alpha-glucosidase. These data on specific interaction between the galactosylated form of alpha-glucosidase and asialoglycoprotein receptor are discussed in connection with the problem of directed transport of the enzyme into liver parenchymatous cells by means of receptor-dependent endocytosis, which may be of importance in development of enzymotherapy of hereditary lysosomal enzymopathies.
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PMID:[Chemical galactosylation of acid alpha-glucosidase to provide directed transport of the enzyme into lysosomes of liver parenchymal cells]. 282 27

In investigations on the intracellular transport route(s) of lysosomal enzymes in polarized epithelial cells, we used immunocytochemical methods to localize lysosomal alpha-glucosidase in human small-intestinal epithelial cells. Two monoclonal antibodies which can discriminate between different biosynthetic forms of this enzyme were used. One monoclonal antibody, 43D1, which recognizes all forms of the enzyme, showed labeling of the Golgi apparatus, the lysosomes and, unexpectedly, of the brush border of the cells. Multivesicular bodies were free of label. In contrast, monoclonal antibody 43G8, which recognizes all forms except the 110,000 Da precursor of alpha-glucosidase, showed labeling of the lysosomes only. This leads us to conclude that the 110,000 Da precursor form of alpha-glucosidase is present in the Golgi apparatus and the brush border of human small-intestinal epithelial cells. Moreover, biochemical experiments show that this precursor copurifies with sucrase, a typical brush-border marker, when a partially purified microvilli fraction is prepared.
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PMID:Immunocytochemical demonstration of the lysosomal enzyme alpha-glucosidase in the brush border of human intestinal epithelial cells. 306 58

We measured the activity of a non-lysosomal alpha-glucosidase with pH optimum near 6.0 in serum from a wide variety of patients, using the fluorogenic substrate, 4-methylumbelliferyl-alpha-D-glucopyranoside. Acutely ill patients with cystic fibrosis (CF) demonstrated significant increases in alpha-glucosidase compared with CF outpatients. The former group of CF patients experienced far more severe chronic pulmonary disease than did the latter, whereas both groups had similar degrees of gastrointestinal impairment. Patients with pancreatitis associated with trauma or complicated by severe necrosis, hemorrhage, or abscess also displayed greater increases in alpha-glucosidase than did patients with uncomplicated (edematous) pancreatitis. For CF outpatients and patients with either edematous pancreatitis or pancreatic cancer, the alpha-glucosidase activity was similar to that for the general hospital-patient population. Corresponding changes were not observed for other measured serum glycosidases (alpha-fucosidase, alpha-mannosidase, beta-glucuronidase, beta-N-acetylglucosaminidase). Measurement of serum alpha-glucosidase may be of value in assessing the clinical course in CF and in differentiating necrotizing from edematous pancreatitis.
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PMID:Measurement of alpha-glucosidase activity in serum from patients with cystic fibrosis or pancreatitis. 351 92


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