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)

The alpha-glucosidase specific for the hydroxylysine-linked disaccharide units of collagens (or 2-0-alpha-D-glucopyranosyl-5-0-beta-D-galactopyranosylhydroxy-L-lysine glucohydrolase) has been measured in kidney cortex and brain cortical tissue of streptozotocin diabetic rats after 19, 23 or 28 weeks of diabetes and of aged rats 22 months old. Increased specific activities of the enzyme have been found repeatedly in the dialyzed homogenates and the 7.2 X 10(6) g.min supernatants of kidney and brain at the various stages of diabetes when compared with age-matched controls; the specific activities returned to a normal level after insulin treatment. Similar increased specific activities were observed in kidney and brain of the aged normoglycemic rats when compared with young adult rats. In diabetic kidney cortex, beta-galactosidase and p-nitrophenyl-alpha-D-glucoside glucosidase specific activities were decreased in contrast to the increase of glucosyl-galactosyl-hydroxy-lysine glucohydrolase. In kidney cortex of the aged rats, beta-galactosidase activity was also decreased, but p-nitrophenyl-alpha-D-glucoside glucosidase was increased. In both diabetic and aged rats, thickening of the kidney glomerular basement membranes was confirmed; thickening of the brain cortical capillary basement membranes was also observed. Thus in the diabetic and aged animals, the increased glucosyl-galactosyl-hydroxylysine glucohydrolase specific activity was associated with basement membrane thickening in the kidney and the brain.
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PMID:Studies on the alpha-glucosidase specific for collagen disaccharide units: variations associated with capillary basement membrane thickening in kidney and brain of diabetic and aged rats. 716 52

Human hepatitis B virus (HBV) envelopes contain three distinct glycoproteins called L, M, and S HBsAg. Each is posttranslationally modified to contain N-linked oligosaccharides. N-linked oligosaccharides, after attachment to a polypeptide backbone, are processed by enzymes within the endoplasmic reticulum (ER). There is uncertainty about what role, if any, these N glycans and their modification in the ER play in the function of the HBV envelope proteins. By treating hepatoblastoma cultures which secrete HBV (HepG 2.2.15 cells) with inhibitors of different steps of the glycosylation and glycan modifying pathway, we provide evidence that glycosylation and the first step in the processing pathway are necessary for virion, but not subviral particle, secretion. That is, using a highly sensitive immunoprecipitation/polymerase chain reaction system, enveloped HBV could not be detected in the medium of HepG2.2.15 cells incubated with tunicamycin. However, HBV subviral particle secretion was not prevented by tunicamycin. Moreover, inhibitors of alpha-glucosidase I (the first step in the glycan processing pathway) also prevented virion secretion. Inhibitors of mannose trimming (a later step) and glycolipid synthesis, did not prevent virion secretion, defining the limits of the glycosylation requirements in secretion. These results demonstrate a requirement for N-glycosylation and glucosidase processing in the secretion of virions and further distinguish between the requirements for virion and subviral particle secretion.
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PMID:Evidence that N-linked glycosylation is necessary for hepatitis B virus secretion. 749 90

Three castrated male Holstein cattle (423 (SD 19)kg live weight) fitted with elevated carotid artery, portal, and mesenteric venous catheters, and abomasal and ileal cannulas were used to study small-intestinal starch digestion. The cattle were infused abomasally with water (275 ml/h), glucose (66 g/h), maize dextrin (66 g/h) or maize starch (66 g/h) in an incomplete Latin square design, with eight infusion periods. Infusion with carbohydrate resulted in higher arterial glucose concentrations and greater net portal glucose flux than when cattle were infused with water. Arterial glucose concentration and net portal glucose flux were highest when glucose was infused. In the small intestine, 85% of abomasally-infused glucose, 78% of infused dextrin, and 66% of infused starch disappeared. Of the carbohydrate that disappeared in the small intestine, that which could be accounted for as net portal glucose flux was 73% for glucose, 60% for dextrin, and 57% for starch. Ileal digesta contained unpolymerized glucose, and short-chain soluble alpha-glucoside. Of the infused dextrin flowing past the ileum (14 g/h), 0.3 g/h was glucose, 6.2 g/h was soluble alpha-glucoside, and 7.5 g/h was insoluble alpha-glucoside. Of the infused starch flowing at the ileum (22.2 g/h), 0.9 g/h was glucose, 5.3 g/h was soluble alpha-glucoside, and 15.9 g/h was insoluble alpha-glucoside. The average chain lengths of the soluble alpha-glucosides in ileal digesta were 2.07 and 2.36 for dextrin and starch infusions respectively, indicating mostly di- and to a lesser extent trisaccharides. We conclude that (1) when 66 g raw starch is presented to the small intestine per h, about half of the intestinal disappearance appears as glucose in the portal vasculature, and (2) alpha-1,4 glucosidase (EC 3.2.1.20) activity at the brush border is the rate-limiting step to small-intestinal starch digestion in cattle.
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PMID:Abomasal glucose, maize starch and maize dextrin infusions in cattle: small-intestinal disappearance, net portal glucose flux and ileal oligosaccharide flow. 762 94

The way in which the human epididymis modifies spermatozoa during their sojourn in this structure might be clarified by knowledge of the nature of its secretions. We have examined the presence of several lysosomal hydrolases in human epididymal tissue and fluids, and their synthesis and secretion by monolayer cultures. Tissues were obtained from men undergoing orchidectomy for prostatic carcinoma. The enzymes cathepsin D and acid alpha-glucosidase were localised in the lysosomes of epithelial cells from the corpus epididymidis, by an immunocytochemical technique. Cathepsin D was also found in epithelial cells of the efferent ducts within lysosomes, apical vesicles and multivesicular bodies. No immunolocalisation of acid glucosidase in the efferent ducts or on the microvilli of the corpus was demonstrable. Cathepsin D, beta-hexosaminidase (N-acetylglucosaminidase) and alpha-glucosidase were measurable in the luminal fluid from the human corpus epididymidis; beta-hexosaminidase was secreted into the culture medium by confluent monolayers of epididymal and efferent duct cells. Immunoprecipitation of cell extracts and culture medium of these cultures incubated with 35S-methionine revealed that the precursors of cathepsin D and beta-hexosaminidase were synthesized and secreted by such monolayers. Thus, active lytic enzymes are secreted by the human epididymis and could modify sperm membranes.
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PMID:Immunocytochemical localisation of some lysosomal hydrolases, their presence in luminal fluid and their directional secretion by human epididymal cells in culture. 778 Oct 38

Trehazolin, a new trehalase inhibitor isolated from the culture broth of Micromonospora, was reported to be a highly specific inhibitor for porcine and silk worm trehalases with IC50 values of 5.5 x 10(-9) and 3.7 x 10(-9) M, respectively (O. Ando, H. Satake, K. Itoi, A. Sato, M. Nakajima, S. Takashi, H. Haruyama, Y. Ohkuma, T. Kinoshita, and R. Enokita (1991) J. Antibiot. 44, 1165-1168). We also found that trehazolin is a very powerful and quite specific inhibitor against purified pig kidney trehalase, giving an IC50 value of 1.9 x 10(-8) M. Lineweaver-Burk plots showed that this compound was a competitive inhibitor of the trehalase. However, even at concentrations of 200 micrograms/ml, trehazolin did not inhibit the rat intestinal maltase or sucrase, yeast alpha-glucosidase or almond beta-glucosidase. Validoxylamine A and validamycin A, two other trehalase inhibitors, showed potent competitive inhibition against purified pig kidney trehalase, with IC50 values of 2.4 x 10(-9) and 2.5 x 10(-4) M, respectively. On the other hand, validoxylamine A was almost inactive against rat intestinal sucrase and maltase, with some inhibition being observed at millimolar concentration. A number of other glucosidase inhibitors, such as MDL 25637, castanospermine, and deoxynojirimycin were also tested against the purified trehalase and showed reasonable inhibitory activity.
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PMID:Inhibitors of pig kidney trehalase. 786 39

The present paper addresses the question how alpha-glucosidase inhibitors affect glucose homeostasis. To facilitate this already established data on the effects of induced malabsorption on gut hormones such as gastric inhibitory polypeptide (GIP) in connection with preliminary findings which deal with the new incretin hormone glucagon-like peptide 1 (7-36) amide (GLP-1) are discussed. To emphasize the possibly important impact of a regulated GLP-1 release in response to glucosidase inhibitor treatment we evaluate the recently introduced concept of 'glucose competence' of pancreatic beta-cells. The slowing of nutrient (i.e. glucose) absorption by therapeutic means (for example, acarbose) could supplement a new approach in the treatment of type 2 diabetics which would utilize the well-preserved insulinotropic activity of GLP-1 in these patients, its glucagon-lowering effect, and its possible inhibition of gastric emptying rates, the latter helping to reduce the requirement for rapid insulin secretory responses as is intended while using alpha-glucosidase inhibitor treatment.
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PMID:Intestinal effects of alpha-glucosidase inhibitors: absorption of nutrients and enterohormonal changes. 800 23

Neutral alpha-glucosidase was isolated from rat liver by Sephadex G-150 gel filtration and polyacrylamide gel electrophoresis at pH 8.9. The enzyme was found to exist in two major forms: alpha-glucosidase AB and alpha-glucosidase C. The neutral alpha-glucosidase C was purified to apparent homogeneity and biochemically characterized. The enzyme form accounts for 25-30% of the total enzyme activity, has a pH optimum at 6.0-6.5 and is thermostable. The apparent Km values for alpha-glucosidase C with maltose, MUF-alpha-D-glucopyranoside and glycogen as substrates were 1.22 mM, 0.47 mM and 68.9 mg, respectively. The finding that glycogen can serve as substrate for neutral alpha-glucosidase C suggests its involvement in glycogen metabolism.
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PMID:Rat liver neutral alpha-glucosidase: isolation and characterization. 803 18

Bromoconduritol inhibits the p-nitrophenyl-glucosidase and maltase activities of glucosidase II purified from rat liver, an enzyme that removes the two alpha-1,3-linked glucose residues of the protein-bound oligosaccharide Glc2Man9GlcNAc2 in the processing of N-glycoproteins. The inactivation process exhibits pseudo-first-order kinetics. Previously, we have demonstrated the occurrence of two binding (active) sites in the glucosidase II for the substrates p-nitrophenyl alpha-D-glucopyranoside (pNphGlc) and maltose (high- and low-affinity sites). The inhibition kinetic studies with bromoconduritol indicate that the high- and low-affinity sites for pNphGlc correspond to high- and low-affinity sites for maltose, respectively. Bromoconduritol has no effect on the binding of the substrates (pNphGlc and maltose) to the high-affinity site, although it does modify the low-affinity site and hinders the binding of the two indicated substrates to this site. These results, together with previous reports, have prompted us to propose a new kinetic model of binding and hydrolysis of the physiological substrate of the enzyme, in which the outermost glucose residue would bind and be released at the high-affinity site, whereas the innermost glucose residue would do so at the low-affinity site.
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PMID:Effect of bromoconduritol on glucosidase II from rat liver. A new kinetic model for the binding and hydrolysis of the substrate. 834 83

Castanospermine is an indolizidine alkaloid that is found in the seeds of the Australian tree Castanospermum australe. These seeds have been reported to be toxic to animals and to cause severe gastrointestinal upset. In order to determine whether castanospermine is responsible for this toxicity, the alkaloid was injected into young mice or rats, and its effects on various intestinal disaccharidases were determined. Another indolizidine alkaloid, the alpha-mannosidase inhibitor swainsonine, was also tested to compare its effects to those of castanospermine. Castanospermine strongly and rapidly inhibited the activity of the disaccharidases, sucrase, maltase, and trehalase, with sucrase being the most sensitive to inhibition. The loss of activity of these enzymes, especially sucrase, in injected animals appeared to be due to a direct inhibition of enzyme activity, rather than to a change in the structure of the glycan chains of the enzyme, since only minor alterations in carbohydrates were observed. On the other hand, swainsonine, when injected into animals, also profoundly decreased the activity of the sucrase, but this alkaloid had no direct effect on sucrase activity although it did markedly alter the carbohydrate nature of this glycoprotein. This change in oligosaccharide structure may affect protein conformation, stability, or targeting, any or all of which may in turn affect activity. In in vitro studies with the purified enzyme, castanospermine was found to be a competitive inhibitor of intestinal sucrase, but it was a noncompetitive inhibitor of intestinal maltase. A number of other glucosidase inhibitors that inhibit sucrase activity in vitro are also described.
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PMID:The effects of castanospermine and swainsonine on the activity and synthesis of intestinal sucrase. 848 56

N-glycosylation of the human immunodeficiency virus type-1 envelope (Env) glycoprotein precursor (gp160) occurs by transfer of Glc3Man9GlcNAc2 onto the nascent protein. Maturation then occurs via cleavage of the three Glc residues, which starts during translation. These events are considered necessary to create Env functional conformation: treatment with "alpha"-glucosidase inhibitors, but not alpha-mannosidase inhibitors (i) impairs gp160 cleavage into gp120 and gp41, (ii) diminishes the accessibility of gp120 V3 region, (iii) prevents gp120 binding to its CD4 receptor, and (iv) prevents gp41-mediated membrane fusion. These inhibitors are of therapeutic interest. Here, using a collection of parent and mutant CHO cells that possess mutations in different steps of glycosylation, we reassessed the role of glycans in both the processing and the properties of recombinant gp160 expressed from a vaccinia virus vector. Mutant cells were as follows: Lec23 (which lacks alpha-glucosidase I activity) produces a collection of triglucosylated structures (Glc3Man7-9GlcNAc2); LEC10 (which has increased GlcNAc transferase III activity) produces complex glycans with a bisected GlcNAc residue; Lec1 (which lacks GlcNAc transferase I) and Lec3.2.8.1 (which lacks GlcNAc transferase I and has decreased activity of CMP-NeuNAc and UDP-Gal translocases) produce Man5GlcNAc2 glycans at complex or hybrid sites. As expected, glycosylation of Env produced from mutants was affected but, irrespective of the glycosylation phenotype, (i) similar quantities of Env were synthesized, (ii) the immunoreactivity of V3 was similar, (iii) gp160 was efficiently cleaved into gp120 and gp41, (vi) Env was exposed at the cell membrane, (v) secreted gp120 bound CD4, and (vi) membrane gp41 was able to induce membrane fusion with CD4+ cells. Thus, the glycosylation alterations examined are dispensable for Env processing and biological activity in CHO cells. In particular, removal of the three outer Glc residues was not required per se for Env folding in this system because functional Env is obtained from Lec23 cells: it appears therefore that lack of modification is not equivalent to drug inhibition of modification. These data are discussed in the light of previous reports describing the use of glycosidase inhibitors to alter glycosylation.
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PMID:Biological properties of recombinant HIV envelope synthesized in CHO glycosylation-mutant cell lines. 861 25


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