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

We investigated the relation between activities of islet glycogenolytic alpha-glucosidehydrolases and insulin secretion induced by glucose and 3-isobutyl-1-methylxanthine (IBMX) by means of suppressing 1) insulin release (Ca2+ deficiency) and 2) islet alpha-glucosidehydrolase activity (selective inhibition by the deoxynojirimycin derivative miglitol). Additionally, the in vivo insulin response to both secretagogues was examined. We observed that, similar to glucose-induced insulin release, islet glycogenolytic hydrolases (acid amyloglucosidase, acid alpha-glucosidase) were highly Ca2+ dependent. Acid phosphatase, N-acetyl-beta-D-glucosaminidase, or neutral alpha-glucosidase (endoplasmic reticulum) was not influenced by Ca2+ deficiency. In Ca2+ deficiency IBMX-induced insulin release was unaffected and was accompanied by reduced activities of islet alpha-glucosidehydrolases. Miglitol strongly inhibited glucose-induced insulin release concomitant with a marked suppression of islet alpha-glucosidehydrolase activities. Direct addition of miglitol to islet homogenates suppressed acid amyloglucosidase [half-maximal effective concentration (EC50) approximately 10(-6) M] and acid alpha-glucosidase. Acid phosphatase and N-acetyl-beta-D-glucosaminidase were unaffected. The miglitol-induced inhibition of glucose-stimulated insulin release was dose dependent (EC50 approximately 10(-6) M) and displayed a remarkable parallelism with the inhibition curve for acid amyloglucosidase. The in vivo insulin secretory response to glucose was markedly reduced in dystrophic mice (low amyloglucosidase), whereas the response to IBMX was unaffected. In summary, islet glycogenolytic hydrolases are Ca2+ dependent, and acid amyloglucosidase is directly involved in the multifactorial process of glucose-induced insulin release. In contrast the mechanisms of IBMX-stimulated insulin secretion operate independently of these enzymes. The effects of miglitol, a drug currently used in diabetes therapy, deserves further investigation.
 ...
PMID:Ca2+ deficiency, selective alpha-glucosidehydrolase inhibition, and insulin secretion. 768 25

Mobilization of Ca2+ from the endoplasmic reticulum (ER) suppresses translational initiation and inhibits post-translational processing and secretion of glycoproteins. This study explores the mechanism whereby ionomycin, a Ca2+ ionophore, and thapsigargin, an ER Ca(2+)-ATPase inhibitor, promote retention of alpha 1-antitrypsin (alpha 1-AT) bearing high mannose, endoglycosidase H (Endo H)-sensitive oligosaccharide side chains within the ER of HepG2 cells. Arrest occurred at the removal of mannose residues such that intermediates with Man7-9GlcNAc2 side chains accumulated with the Man8-9GlcNAc2 structures predominating. Maturation of alpha 1-AT bearing Man5-6GlcNAc2 side chains was unaffected. Inhibition of alpha 1-AT processing by ionomycin occurred independently of translational suppression. Forms of alpha 1-AT identical to those retained with ionomycin or thapsigargin were observed upon treatment with the alpha-1,2-mannosidase inhibitor 1-deoxymannojirimycin whereas castanospermine, an inhibitor of ER alpha-glucosidase I, produced different forms of the glycoprotein. Neither inhibitor impaired transport or secretion of alpha 1-AT. With brefeldin A, which causes redistribution of Golgi enzymes to the ER, alpha 1-AT was retained intracellularly but acquired resistance to Endo H. With ionomycin, thapsigargin, or 1-deoxymannojirimycin-treated cells, however, brefeldin A failed to promote further processing of the glycoprotein. Possible mechanisms for the suppression of alpha 1-AT processing at the alpha-1,2-mannosidase step by Ca(2+)-mobilizing agents are discussed. Excepting tunicamycin, traditional inhibitors of protein processing did not affect amino acid incorporation.
 ...
PMID:Role of endoplasmic reticular calcium in oligosaccharide processing of alpha 1-antitrypsin. 838 May 85

1. Body weight, digestive organ weights, and activities of disaccharidases (maltase and saccharase) activities were determined from day of hatch to 21 d of age in meat- and egg-type chickens. Blood plasma was analysed for enzyme activities and metabolite concentration. 2. In meat-type chickens food intake and growth rate were about 3-fold those in egg-type chickens. Food efficiency was superior in meat-type chickens throughout the experimental period. 3. Meat-type chickens hatched with disaccharidase activities exceeding those found in their egg-type counterparts 2- to 5-fold. From 7 d of age on, this trend reversed, i.e. activity was much higher in egg-type than in meat-type chickens. 4. Blood plasma amylase activity increased gradually in meat-type chickens and was higher than in egg-type chickens to 14 d of age. No breed differences were observed for alkaline phosphatase or lactate dehydrogenase activities during the experimental period. 5. Blood plasma concentrations of total protein, albumin, glucose, and calcium, were lower in meat than in egg-type chickens.
 ...
PMID:Comparative development of digestive organs, intestinal disaccharidases and some blood metabolites in broiler and layer-type chicks after hatching. 877 45

The effect of supplementing a cornsoybean diet (C) with glucose (G) or maltose (M) on young broilers (from hatch to 3 wk of age) affected by stunting syndrome (SS) was studied. Stunting syndrome was induced by orally administering an inoculum prepared from the intestines of SS broiler chicks. Relative to the M diet, the G diet improved growth and feed utilization and increased feed intake in naive (NA) control chickens. The C diet was intermediate in this respect. In contrast to the NA chickens, diet did not affect growth or feed utilization in SS chicks. Changes in the relative weights of the gastrointestinal tract segments were evident by 1 wk of age and hypertrophy of these segments persevered to 3 wk of age. Stunting syndrome infection was accompanied by a significant increase in pancreatic trypsin-specific activity during Weeks 1 and 2, and in chymotrypsin activity at 1 wk. During this time, amylase-specific activity was not affected. At 3 wk of age, the specific activities of amylase, trypsin, and chymotrypsin in the pancreas were lower in the inoculated vs control birds. Whereas no significant effect of SS was observed with activities of amylase in the intestinal contents, trypsin activity was higher in SS chicks at 1 wk, and that of chymotrypsin lower during Weeks 2 and 3. Relative to NA chicks, the maltase and saccharase activities of SS chicks were much lower during Week 1, but increased later on and were similar to NA chick values at 2 and 3 wk. Whereas the level of blood plasma proteins did not vary from 1 to 3 wk in the NA chicks, it increased gradually in SS chicks to a level that significantly exceeded that in their NA counterparts. Blood plasma glucose and triglyceride levels were slightly lower in the SS chicks (NS), and the blood plasma cholesterol level was significantly reduced during Week 2. Relative to NA chicks, SS infection caused a significant increase in plasma calcium during Weeks 2 and 3, accompanied by a significant reduction in blood plasma phosphorus at 2 wk only. No difference was observed in the blood plasma level of uric acid, which peaked in both treatments during Week 2, or in D-beta-hydroxybutyric acid level, which was quite stable during the experimental period. Stunting syndrome infection was accompanied by a dramatic increase in amylase and alkaline phosphatase activities in the blood plasma, and by a slight but significant decrease in activity of lactic dehydrogenase. Stunting syndrome was concluded to be an affliction not only of digestion but also of metabolism. The main depression in growth caused by SS inoculation is probably due to metabolic alterations beyond those of digestion and absorption.
 ...
PMID:Stunting syndrome in broilers: effect of glucose or maltose supplementation on digestive organs, intestinal disaccharidases, and some blood metabolites. 905 21

BT-R1, the Manduca sexta midgut receptor for the crystal toxin Cry1Ab produced by Bacillus thuringiensis ssp. berliner, was partly purified by gel filtration from M. sexta brush border membrane vesicles in the presence of the detergent CHAPS. Fractions containing BT-R1 were tested for their stability against degradation as indicated by retention of Cry1Ab binding on ligand blots. At 4 degrees C and pH 7.4 in the presence of Ca2+, BT-R1 was stable for up to 48 h but a 65% loss of binding was observed after 100 h. Under the same conditions, no loss of binding was observed in the presence of EGTA after 100 h. Cry1Ab binding decreased markedly as pH increased from 6 to 10 for incubations of 24 h at 4 degrees C. Increasing the temperature of incubation from 4 to 37 degrees C also decreased Cry1Ab binding. Neither metal ions nor free sulfhydryl groups are involved in Cry1Ab binding to BT-R1. A trypsin-like, metal-ion-dependent proteolytic activity co-eluted with BT-R1 during gel filtration. This endoproteolytic activity was unaltered by the addition of Cry1Ab. BT-R1 did not co-elute with peaks of aminopeptidase, alkaline phosphatase, alpha-glucosidase, beta-glucosidase and beta-galactosidase activities. When BT-R1 in the gel filtration fraction was further purified on a Mono Q anion exchange column, partial separation of the trypsin-like activity from BT-R1 was observed. BT-R1 could be removed from the appropriate Mono Q fraction by immunoprecipitation with only a slight decrease in this activity. These results demonstrate that there is no copurification of BT-R1 and these enzymes and that BT-R1 is unlikely to form complexes with them. Binding of Cry1Aa and Cry1Ac to BT-R1 in gel filtration fractions is similar to that of Cry1Ab, indicating that BT-R1 may be the high-affinity receptor for the Cry1A toxins. Binding of Cry1Ab to a 120 kDa protein has not been observed in this study.
 ...
PMID:Further characterization of BT-R1, the cadherin-like receptor for Cry1Ab toxin in tobacco hornworm (Manduca sexta) midguts. 930 95

The cloning, sequencing and structural characterization of a gene encoding a thermostable alpha-1,4-glucosidase from Thermomonospora curvata is described. DNA sequence analysis revealed four open reading frames designated aglA, aglR, aglE and aglF. The aglA gene encodes a thermostable alpha-1,4-glucosidase from T. curvata and is situated between two genes, aglR and aglE. Genes aglA, aglE and aglF are transcribed in the same direction, while aglR is transcribed in the opposite direction. By comparing the amino acid sequence of the alpha-1,4-glucosidase from T. curvata with other alpha-glucanases, it appears that the enzyme is a member of the alpha-amylase family. The proteins of this family have an (alpha/beta)8 barrel super secondary structure. The topology of the alpha-1,4-glucosidase was predicted by computer-assisted analysis. The topology of the secondary structures of the alpha-1,4-glucosidase resembles the structure of barley alpha-amylase, but the primary structure resembles most closely the oligo-1,6-glucosidase from Bacillus cereus. Putative catalytic residues (D221, E281 and D343) and calcium binding residues (N116, E179, D191, H224 or G225) are proposed.
 ...
PMID:Molecular characterization of the Thermomonospora curvata aglA gene encoding a thermotolerant alpha-1,4-glucosidase. 1079 37

Alkaliphilic bacteria were isolated from soil and water samples obtained from Ethiopian soda lakes in the Rift Valley area--Lake Shala, Lake Abijata, and Lake Arenguadi. Starch-hydrolyzing isolates were selected on the basis of their activity on starch agar plate assay. Sixteen isolates were chosen, characterized, and subjected to 16S rRNA gene sequence analysis. All the isolates were gram positive and catalase- and beta-galactosidase positive. All isolates except one were motile endospore-forming rods and were found to be closely related to the Bacillus cluster, being grouped with Bacillus pseudofirmus, Bacillus cohnii, Bacillus vedderi, and Bacillus agaradhaerens. The one exception had nonmotile coccoid cells and was closely related to Nesterenkonia halobia. The majority of the isolates showed optimal growth at 37 degrees C and tolerated salinity up to 10% (w/v) NaCl. Both extracellular and cell-bound amylase activity was detected among the isolates. The amylase activity of two isolates, related to B. vedderi and B. cohnii, was stimulated by ethylenediaminetetraacetic acid (EDTA) and inhibited in the presence of calcium ions. Pullulanase activity was expressed by isolates grouped with B. vedderi and also most of the isolates clustered with B. cohnii; cyclodextrin glycosyltransferase was expressed by most of the B. agaradhaerens-related strains. Minor levels of alpha-glucosidase activity were detected in all the strains.
 ...
PMID:Starch-hydrolyzing bacteria from Ethiopian soda lakes. 1135 57

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 81C6; Adefovir dipivoxil, Agalsidase alfa, AGM-1470, albumin interferon alfa, alefacept, alosetron hydrochloride, anakinra, anti-CTLA-4 Mab, aprepitant, aripiprazole, atazanavir; BAY-43-9006, BBR-3438, beta-L-Fd4C, bimatoprost, bortezomib, bosentanBR96-doxorubicin; Caspofungin acetate, ciclesonide, cilengitide, cilomilast, COL-1621, COL-3, CpG-7909, cyclosporine; DCVax-Brain, dexmethylphenidate hydrochloride, dexosome vaccine (melanoma), donepezil hydrochloride, drotrecogin alfa (activated), DTI-015, [99Tc]-DTPA-mannosyldextran, duloxetine hydrochloride; Emivirine, emtricitabine, entecavir, epothilone B, estradiol-MNP, etonogestrel/etonogestrel/ethinylestradiol, etoricoxib; Febuxostat, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GVS-111; Heparinase I, HspE7, human alpha-glucosidase, human insulin; Imatinib mesylate, INGN-241, interferon alfa B/D hybrid, interferon alfa Biphasix, ISIS-14803; Lanicemine hydrochloride, 1311-lipiodol, liposome-encapsulated mitoxantrone, lixivaptan, lumiracoxib, lupus-AHP, LY-466700; Marimastat, MEN-10755, micafungin sodium; Nitronaproxen, NSC-683864 Omalizumab, oral insulin; Palonosetron hydrochloride, peginterferon alfa-2a, pimecrolimus, pralnacasan, pramlintide acetate, pregabalin, pyrazoloacridine; R-165335, ranolazine, risperidone, RPR-109881;, RSD-1235, Satraplatin, seocalcitol, sertindole, SMART anti-interferon gamma antibody, sulfasalazine; T-138067, TAK-013, tegaserod maleate, telithromycin, tenofovir disoproxil fumarate, teriparatide, tiotropium bromide, tipifarnib, TP-38; Valdecoxib, vatalanib succinate, voriconazole; ZD-9331.
 ...
PMID:Gateways to clinical trials. 1269 Jul 8

The sea urchin embryo is a model for studying cellular interactions that occur in higher organisms because of its availability, transparency, and accessibility to molecular probes. In previous studies, we found that the mannose/glucose-binding lectin Lens culinaris agglutinin entered living sea urchin embryos, bound to specific cell types and caused exogastrulation, when the developing gut (archenteron) falls out of the embryo proper. We have proposed that the lectin bound to sugar-containing ligands, thus preventing attachment of the archenteron to the blastocoel roof, resulting in exogastrulation. Here, we have continued our study of cellular interactions in this model using Lytechinus pictus sea urchin embryos, and have found that inhibitors of glycoprotein/proteoglycan synthesis, tunicamycin and sodium selenate, and the specific glycosidases, beta-amylase, alpha-glucosidase, and alpha-mannosidase, all inhibit archenteron organization, elongation, and attachment to the blastocoel roof in viable swimming embryos. We also show that single cells obtained by disaggregation of 32-h-old sea urchin embryos bind to L. culinaris agglutinin- and concanavalin A-derivatized beads; the binding is blocked by alpha-methyl mannose, but not l-fucose. These cells also bind to beads derivatized with mannan. These results provide evidence for a role of carbohydrate-containing molecules in cellular interactions in sea urchin gastrulation. In a second set of experiments, we found that the supernatant obtained by disaggregation of 24-32-h-old L. pictus embryos in calcium- and magnesium-free sea water contains molecules that cause exogastrulation, archenteron disorganization, inhibition of archenteron elongation and inhibition of archenteron attachment to the blastocoel roof in viable swimming embryos. We propose that the supernatant contains ligands and/or receptors that mediate archenteron development and attachment to the blastocoel roof and are released when embryos are disaggregated into single cells. These studies may lead to a better understanding of the molecular basis of mechanisms that control cellular interactions during development.
 ...
PMID:Carbohydrate involvement in cellular interactions in sea urchin gastrulation. 1514 30

Five types of oral antihyperglycemic drugs are currently approved for the treatment of diabetes: biguanides, sulfonylureas, meglitinides, glitazones, and alpha-glucosidase inhibitors. The cardiovascular effects of the most commonly used antidiabetic drugs in these groups are briefly reported, in an attempt to improve knowledge and awareness regarding their influences and potential risks when treating patients with coronary artery disease (CAD). Regarding biguanides, gastrointestinal disturbances such as diarrhea are frequent, and the intestinal absorption of group B vitamins and especially folate is impaired during chronic therapy. This deficiency may lead to increased plasma homocysteine levels which, in turn, accelerate the progression of vascular disease due to adverse effects on platelets, clotting factors, and endothelium. The existence of a graded association between homocysteine levels and overall mortality in patients with CAD is well established. In addition, metformin may lead to lethal lactic acidosis, especially in patients with clinical conditions that predispose to this complication, such as heart failure or recent myocardial infarction. Sulfonylureas avoid ischemic preconditioning. During myocardial ischemia, they may prevent the opening of the ATP-dependent potassium channels, impeding the necessary hyperpolarization that protects the cell by blocking calcium influx. Meglitinides may exert similar effects, due to their analogous mechanism of action. During treatment with glitazones, edema has been reported in 5% of patients, and these drugs are contraindicated in diabetics with NYHA class III or IV cardiac status. The long-term effects of alpha-glucosidase inhibitors on morbidity and mortality rates and on diabetic micro- and macrovascular complications are yet unknown. The combined sulfonylurea/metformin therapy reveals additive effects on mortality. It is concluded that(1) four of the five oral antidiabetic drug groups present proven or potential cardiac hazards;(2) these hazards are not mere "side effects", but are deeply rooted in the drugs' mechanism of action;(3) current data indicate that the combined glibenclamide/metformin therapy seems to present special risk and should be avoided in the long-term management of type 2 diabetics with proven CAD; and(4) customized antihyperglycemic pharmacological approaches should be investigated for optimal treatment of diabetic patients with heart disease.
 ...
PMID:Oral antidiabetic therapy in patients with heart disease. A cardiologic standpoint. 1516 55


<< Previous 1 2 3 4 5 Next >>