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:3.2.1.20 (alpha-glucosidase)
4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Duodenal biopsies were collected from 38 subjects (24 female and 14 male) ranging in age from 55 to 91 years. Evidence of bacterial contamination of the small bowel (BCSB) was sought at the same time by bacterial culture of duodenal aspirates and by hydrogen and [14C]glycocholic acid breath tests; subjects were considered to be positive for BCSB if any one of the three tests was abnormal. Biopsies were analyzed for six brush-border membrane enzyme activities: maltase, sucrase, lactase, alkaline phosphatase, leucine aminopeptidase, and alpha-glucosidase. Analysis of covariance with age as the covariate indicated no significant effect of age on the specific activities of these enzymes. Mucosal Na(+)-dependent glucose transport was quantified in brush-border membrane vesicles prepared from the biopsies. In all groups, glucose transport at 20-30 sec was greater (ranging from mean values of 2.45 to 3.66 times) than at 45 min, consistent with Na(+)-coupled glucose transport, and no significant effect of age was observed. BCSB had no significant effect on specific activities of any of the duodenal mucosal hydrolases but was associated with reduced (P = 0.05) brush-border glucose transport. None of the variables studied was significantly affected by the gender of subjects. In conclusion, these biochemical data do not support the contention that reduced capacity for carbohydrate absorption in the elderly is explained by reductions in duodenal brush-border mucosal disaccharidase activities or glucose transport.
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PMID:Duodenal brush-border mucosal glucose transport and enzyme activities in aging man and effect of bacterial contamination of the small intestine. 844 69

Recent work in the synthesis of cyclic phosphonate analogues of glucose [Darrow, J.W.; Drueckhammer, D.G. (1994) J. Org. Chem. 1994, 59, 2976] has been extended to the synthesis of a corresponding phosphonamidate analogue. A phosphonate salt, phosphonate methyl ester, and phosphonamidate analogue were tested as inhibitors of two inverting alpha-glycosidases, (trehalase and glucoamylase), and two retaining glycosidases, (alpha-glucosidase and beta-glucosidase). No inhibition of any of these enzymes was observed with the phosphonate salt or methyl ester. However, the phosphonamidate gave moderate competitive inhibition of the two inverting glycosidases and the retaining alpha-glucosidase but no inhibition of beta-glucosidase. The phosphonamidate showed enhanced binding relative to a simple monosaccharide only with the inverting glycosidases. This enhanced binding is believed to be due to hydrogen bonding interactions between the phosphonamidate group and two active site carboxylate residues implicated in catalysis. The selectivity toward inverting glycosidases is consistent with differences in distance of an active site carboxylate from the anomeric carbon of the glycoside substrate for the inverting versus the retaining glycosidases.
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PMID:A cyclic phosphonamidate analogue of glucose as a selective inhibitor of inverting glycosidases. 887 56

We previously reported that the topical application of ascorbic acid 2-O-alpha-glucoside (AA-2G) suppressed the cutaneous inflammation by ultraviolet irradiation in human and guinea pigs (Miyai et al., Nishinihon J. Dermatol., 58, 439-443 (1996)). In this paper, the effect of AA-2G on the lethal damage induced by ultraviolet B (UVB) was studied using a human keratinocyte cell line, SCC, established from squamous cell carcinoma. The photoprotective effect of AA-2G on cytotoxicity of UVB in SCC cells was dose dependent (0.125-1 mM) and more effective than that of ascorbic acid (AsA) at 1 mM. This protection was completely abolished in the presence of an alpha-glucosidase inhibitor, castanospermine, indicating that release of AsA from this derivative was essential for reduction of the actinic injury. AA-2G significantly suppressed cytotoxicities of hydrogen peroxide and superoxide anion produced by xanthine and xanthine oxidase. AA-2G exhibited a preventive effect against the cytotoxicity produced by tert-butylhydroperoxide, an inducer of lipid peroxidation, in the presence of alpha-tocopherol, but not in the absence of alpha-tocopherol. Cytotoxicity of UVB was also effectively reduced by the combination of AA-2G and alpha-tocopherol. In addition, AA-2G reduced UVB-promoted formation of lipid peroxide and accumulation of lipofuscin, which is known to be a complex of cellular proteins and metabolites of lipid peroxide. These data suggest that AA-2G prevents the acute inflammation induced by UVB irradiation partly through scavenging reactive oxygen species and potentiating the antioxidative activity of alpha-tocopherol.
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PMID:Ascorbic acid 2-O-alpha-glucoside-induced redox modulation in human keratinocyte cell line, SCC: mechanisms of photoprotective effect against ultraviolet light B. 921 80

GLP-1, an incretin hormone of the enteroinsular axis with insulinotropic and glucagonostatic activity, is secreted after nutrient ingestion. GLP-1 is mainly produced by intestinal L-cells in the lower gastrointestinal tract (GIT); simple carbohydrates are absorbed in the upper GIT and alpha-glucosidase inhibition leads to augmented and prolonged GLP-1 release in normal subjects. In a cross-over study, 100 mg acarbose or placebo was administered simultaneously with 100 g sucrose to 11 hyperglycaemic Type 2 diabetic patients poorly controlled with diet and sulphonylureas. Plasma levels of GLP-1, insulin, C-peptide, glugacon, GIP, glucose and H2-exhalation were measured over 6 h. Differences in the integrated responses over the observation period were evaluated by repeated measurement analysis of variance with fasting values used as covariates. With acarbose, sucrose reached the colon 60-90 min after ingestion as indicated by a significant increment in breath hydrogen exhalation (p = 0.005). After an early GLP-1 increment 15 min after sucrose under both conditions, GLP-1 release was prolonged in the acarbose group (p = 0.001; significant from 210 to 360 min.). Initially (0-150 min), glucose (p = 0.001), insulin (p = 0.001), and GIP (p < 0.001) were suppressed by acarbose, whereas later there were no significant differences. Glucagon levels were higher with acarbose in the last 3 h of the 6 h observation period (p = 0.02). We conclude that in hyperglycaemic Type 2 diabetic patients, ingestion of acarbose with a sucrose load leads to elevated and prolonged GLP-1 release.
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PMID:Prolonged and enhanced secretion of glucagon-like peptide 1 (7-36 amide) after oral sucrose due to alpha-glucosidase inhibition (acarbose) in Type 2 diabetic patients. 963 23

Acarbose is an alpha-glucosidase inhibitor approved for the treatment of type 2 diabetes mellitus. Acarbose inhibits carbohydrate digestion, allowing an excessive amount of undigested carbohydrate to reach the colon. Bacterial fermentation of the carbohydrate produces intestinal gas, which can cause flatulence and abdominal pain. Beano, an over-the-counter enzyme preparation (alpha-galactosidase), diminishes intestinal gas production by enhancing the breakdown of certain carbohydrates before they reach the lower intestine. This study was undertaken to investigate whether concomitant administration of Beano and acarbose could reduce the flatulence associated with acarbose and, if so, whether Beano would interfere with the effects of acarbose on postprandial serum glucose concentration. In this randomized, double-masked, placebo-controlled, three-period crossover study, 37 patients with type 2 diabetes mellitus received acarbose 100 mg, acarbose 100 mg plus Beano, or placebo. The study population consisted of 20 males and 17 females who ranged in age from 36 to 72 years (mean, 56 years) and in weight from 62 to 142 kg (mean, 92 kg). Each treatment period consisted of 3 days, during which both acarbose and Beano were given at the beginning of each of three meals. There was a 4-day washout interval between each treatment period. The frequency and severity of flatulence were measured using a score compiled from patient diaries. As an additional measure of intestinal gas production, breath hydrogen concentration was measured on day 3 of each treatment period. Postprandial serum glucose concentration was measured at predetermined times after each morning dose to assess pharmacodynamic activity. Patients who took Beano with acarbose had a significantly lower flatulence score than did those who took acarbose alone (0.79 vs 1.09). Consistent with this finding, breath hydrogen concentration was lower after administration of acarbose plus Beano than with acarbose alone (31.2 ppm vs 50.5 ppm). Beano had variable effects on the ability of acarbose to reduce the postprandial serum glucose concentration. Although postprandial serum glucose levels were higher in patients who received acarbose plus Beano than in those who received acarbose alone, both treatments (with or without Beano) resulted in postprandial serum glucose levels that were significantly lower than those seen with placebo. Therefore, although Beano appeared to diminish the activity of acarbose, postprandial serum glucose concentrations still decreased significantly in patients taking Beano with acarbose. Beano has been shown to alleviate the flatulence accompanying acarbose treatment, but it may also interfere with the glucose-lowering effect of acarbose.
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PMID:Effects of beano on the tolerability and pharmacodynamics of acarbose. 966 65

The origin of seminal leucocytes and their biological significance were investigated in 76 whole ejaculate samples and 27 split ejaculate samples, obtained from patients attending the Zimbabwe Family Planning Council's Spilhaus Infertility Clinic at Harare. The leucocytes were more prevalent in fractions 1 and 2 than in fraction 3, implying that the testis, epididymis and prostate are the major sources of seminal leucocytes. The contribution from the seminal vesicles was minimal. An inverse relation is apparent between leucocyte count and sperm count (p < 0.01). The percentage of abnormal sperms was higher (p < 0.05) and the sperm motility poorer in leucocytospermic samples (p < 0.01). Fructose, the seminal vesicular marker, citric acid, the prostatic marker and alpha-glucosidase, the epididymal marker were not decreased in leucocytospermia. It is concluded that the epididymis and prostate are the major contributors of granulocytes in semen. Leucocytospermia affects sperm morphology and sperm motility but not the accessory sex gland functions. Probably these cytotoxic effects are mediated by hydrogen peroxide due to activation of seminal leucocytes. However, the presence of leucocytospermia in normozoospermic samples is indicative of the possible peaceful coexistence of leucocytes and sperms.
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PMID:Study on the origin of seminal leucocytes using split ejaculate technique and the effect of leucocytospermia on sperm characteristics. 987 48

High-isoelectric-point (pI) alpha-glucosidase was purified 7, 300-fold from an extract of barley (Hordeum vulgare) malt by ammonium sulfate fractionation, ion-exchange, and butyl-Sepharose chromatography. The enzyme had high activity toward maltose (k(cat) = 25 s(-1)), with an optimum at pH 4.5, and catalyzed the hydrolysis by a retaining mechanism, as shown by nuclear magnetic resonance. Acarbose was a strong inhibitor (K(i) = 1.5 microM). Molecular recognition revealed that all OH-groups in the non-reducing ring and OH-3 in the reducing ring of maltose formed important hydrogen bonds to the enzyme in the transition state complex. Mass spectrometry of tryptic fragments assigned the 92-kD protein to a barley cDNA (GenBank accession no. U22450) that appears to encode an alpha-glucosidase. A corresponding sequence (HvAgl97; GenBank accession no. AF118226) was isolated from a genomic phage library using a cDNA fragment from a barley cDNA library. HvAgl97 encodes a putative 96.6-kD protein of 879 amino acids with 93.8% identity to the protein deduced from U22450. The sequence contains two active site motifs of glycoside hydrolase family 31. Three introns of 86 to 4,286 bp interrupt the coding region. The four exons vary from 218 to 1,529 bp. Gene expression analysis showed that transcription reached a maximum 48 h after the start of germination.
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PMID:Purification, enzymatic characterization, and nucleotide sequence of a high-isoelectric-point alpha-glucosidase from barley malt. 1080 44

Important hydrogen bonding interactions between substrate OH-groups in yeast alpha-glucosidases and oligo-1,6-glucosidase from glycoside hydrolase family 13 have been identified by measuring the rates of hydrolysis of methyl alpha-isomaltoside and its seven monodeoxygenated analogs. The transition-state stabilization energy, DeltaDeltaG, contributed by the individual OH-groups was calculated from the activities for the parent and the deoxy analogs, respectively, according to DeltaDeltaG = -RT ln[(Vmax/Km)analog/(Vmax/Km)parent]. This analysis of the energetics gave DeltaDeltaG values for all three enzymes ranging from 16.1 to 24.0 kJ.mol-1 for OH-2', -3', -4', and -6', i.e. the OH-groups of the nonreducing sugar ring. These OH-groups interact with enzyme via charged hydrogen bonds. In contrast, OH-2 and -3 of the reducing sugar contribute to transition-state stabilization, by 5.8 and 4.1 kJ.mol-1, respectively, suggesting that these groups participate in neutral hydrogen bonds. The OH-4 group is found to be unimportant in this respect and very little or no contribution is indicated for all OH-groups of the reducing-end ring of the two alpha-glucosidases, probably reflecting their exposure to bulk solvent. The stereochemical course of hydrolysis by these three members of the retaining family 13 was confirmed by directly monitoring isomaltose hydrolysis using 1H NMR spectroscopy. Kinetic analysis of the hydrolysis of methyl 6-S-ethyl-alpha-isomaltoside and its 6-R-diastereoisomer indicates that alpha-glucosidase has 200-fold higher specificity for the S-isomer. Substrate molecular recognition by these alpha-glucosidases are compared to earlier findings for the inverting, exo-acting glucoamylase from Aspergillus niger and a retaining alpha-glucosidase of glycoside hydrolase family 31, respectively.
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PMID:Substrate recognition by three family 13 yeast alpha-glucosidases. 1185 34

We designed and synthesized hydrogen bond based probes 1-8 with the exception of known glycosidase inhibition mechanisms, and aglycon specificity of 11 different sources of alpha-glucosidases were investigated using their probes. Probe 4 (2,6-anhydro-1-deoxy-1-[(1-oxopentyl-5-hydroxy)amino]-D-glycero-D-ido-heptitol) showed a potent inhibition of S. cerevisiae alpha-glucosidase among all alpha-glucosidases. Probe 4 was found to be a competitive inhibitor for S. cerevisiae alpha-glucosidase with Ki 0.13 mM.
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PMID:Aglycon specificity profiling of alpha-glucosidases using synthetic probes. 1571 13

Alkylation of 1-azafagomine at the 2-N position was achieved by reductive amination of 1-N-acetyl-3,4,6-tri-O-benzyl-1-azafagomine by using aldehydes, palladium hydroxide, and hydrogen in EtOAc/water/acetic acid followed by deprotection. The 2-N-butyl, hexyl, heptyl, nonyl, decyl, and 3-phenylpropyl derivatives were made in this manner, and were tested for inhibition of alpha-glucosidase from yeast, and of beta-glucosidase from almonds. The new compounds were stronger beta-glucosidase inhibitors than 1-azafagomine, but weaker alpha-glucosidase inhibitors.
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PMID:Anomer-selective glycosidase inhibition by 2-N-alkylated 1-azafagomines. 1735 29


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