It has been suggested that Maltase be merged into this article. (Discuss) Proposed since November 2023.
α-Glucosidase (EC 3.2.1.20, (systematic name α-D-glucoside glucohydrolase) is a glucosidase located in the brush border of the small intestine that acts upon α(1→4) bonds:[1][2][3][4][5][6]
The Gene Ontology entry GO:0090599 represents the broad sense of "alpha-glucosidase". It is defined as "catalysis of the hydrolysis of terminal, non-reducing alpha-linked alpha-D-glucose residue with release of alpha-D-glucose." In this sense, "alpha-glucosidase" can encompass a wide range of enzyme activitiess, differing by the linkage of their terminal (1→3, 1→4, or 1→6), the specific identity of their substrate (sucrose, maltose, or starch), among other aspects.[7]
EC 3.2.1.20, the narrow senseedit
The definition associated with Enzyme Commission number 3.2.1.20 is narrower. It requires the linkage to be 1→4, and the preferred substrate to be smaller oligosaccharides (as opposed to larger polysaccharides like starch: alpha-amylase would otherwise be included). Human genes that produce enzymes with activities specified by this EC number include:[8]
MGAM is the "maltase-glucoamylase", found on the intestine brush border.
GAA is the "acid alpha-glucosidase", found in the lysosome.
Synonyms mentioned by the Commission include maltase, glucoinvertase, glucosidosucrase, maltase-glucoamylase, α-glucopyranosidase, glucosidoinvertase, α-D-glucosidase, α-glucoside hydrolase, α-1,4-glucosidase, α-D-glucoside glucohydrolase.[9] These names are not recommended because they may only refer to a specific activity of the enzyme, or a specific protein having this acvitity.
Mechanismedit
α-Glucosidase hydrolyzes terminal non-reducing (1→4)-linked α-glucose residues to release a single α-glucose molecule.[10] α-Glucosidase is a carbohydrate-hydrolase that releases α-glucose as opposed to β-glucose. β-Glucose residues can be released by glucoamylase, a functionally similar enzyme. The substrate selectivity of α-glucosidase is due to subsite affinities of the enzyme's active site.[11] Two proposed mechanisms include a nucleophilic displacement and an oxocarbenium ion intermediate.[11]
Example of an α-glucosidase catalyzed reaction: maltotriose + water → α-glucose
Rhodnius prolixus, a blood-sucking insect, forms hemozoin (Hz) during digestion of host hemoglobin. Hemozoin synthesis is dependent on the substrate binding site of α-glucosidase.[12]
Trout liver α-glucosidases were extracted and characterized. It was shown that for one of the trout liver α-glucosidases maximum activity of the enzyme was increased by 80% during exercise in comparison to a resting trout. This change was shown to correlate to an activity increase for liver glycogen phosphorylase. It is proposed that α-glucosidase in the glucosidic path plays an important part in complementing the phosphorolytic pathway in the liver's metabolic response to energy demands of exercise.[13]
Yeast and rat small intestinal α-glucosidases have been shown to be inhibited by several groups of flavonoids.[14]
Structureedit
α-glucosidase in complex with maltose and NAD+
α-Glucosidases can be divided, according to primary structure, into two families.[11] The gene coding for human lysosomal α-glucosidase is about 20 kb long and its structure has been cloned and confirmed.[15]
Human lysosomal α-glucosidase has been studied for the significance of the Asp-518 and other residues in proximity of the enzyme's active site. It was found that substituting Asp-513 with Glu-513 interferes with posttranslational modification and intracellular transport of α-glucosidase's precursor. Additionally, the Trp-516 and Asp-518 residues have been deemed critical for the enzyme's catalytic functionality.[16]
Kinetic changes in α-glucosidase have been shown to be induced by denaturants such as guanidinium chloride (GdmCl) and SDS solutions. These denaturants cause loss of activity and conformational change. A loss of enzyme activity occurs at much lower concentrations of denaturant than required for conformational changes. This leads to a conclusion that the enzyme's active site conformation is less stable than the whole enzyme conformation in response to the two denaturants.[17]
Disease relevanceedit
Glycogen storage disease type II, also called Pompe disease: a disorder in which α-glucosidase is deficient. In 2006, the drug alglucosidase alfa became the first released treatment for Pompe disease and acts as an analog to α-glucosidase.[18] Further studies of alglucosidase alfa revealed that iminosugars exhibit inhibition of the enzyme. It was found that one compound molecule binds to a single enzyme molecule. It was shown that 1-deoxynojirimycin (DNJ) would bind the strongest of the sugars tested and blocked the active site of the enzyme almost entirely. The studies enhanced knowledge of the mechanism by which α-glucosidase binds to imino sugars.[19]
Diabetes:Acarbose, an α-glucosidase inhibitor, competitively and reversibly inhibits α-glucosidase in the intestines. This inhibition lowers the rate of glucose absorption through delayed carbohydrate digestion and extended digestion time. Acarbose may be able to prevent the development of diabetic symptoms.[20] Hence, α-glucosidase inhibitors (like acarbose) are used as anti-diabetic drugs in combination with other anti-diabetic drugs. Luteolin has been found to be a strong inhibitor of α-glucosidase. The compound can inhibit the enzyme up to 36% with a concentration of 0.5 mg/ml.[21] As of 2016, this substance is being tested in rats, mice and cell culture. Flavonoid analogues have been demonstrated with inhibition activity.[22]
Azoospermia: Diagnosis of azoospermia has potential to be aided by measurement of α-glucosidase activity in seminal plasma. Activity in the seminal plasma corresponds to the functionality of the epididymis.[23]
Antiviral agents: Many animal viruses possess an outer envelope composed of viral glycoproteins. These are often required for the viral life cycle and utilize cellular machinery for synthesis. Inhibitors of α-glucosidase show that the enzyme is involved in the pathway for N-glycans for viruses such as HIV and human hepatitis B virus (HBV). Inhibition of α-glucosidase can prevent fusion of HIV and secretion of HBV.[24]
^Bruni, C.B.; Sica, V.; Auricchio, F.; Covelli, I. (1970). "Further kinetic and structural characterization of the lysosomal α-D-glucoside glucohydrolase from cattle liver". Biochim. Biophys. Acta. 212 (3): 470–477. doi:10.1016/0005-2744(70)90253-6. PMID 5466143.
^Flanagan, P.R.; Forstner, G.G. (1978). "Purification of rat intestinal maltase/glucoamylase and its anomalous dissociation either by heat or by low pH". Biochem. J. 173 (2): 553–563. doi:10.1042/bj1730553. PMC1185809. PMID 29602.
^Larner, J.; Lardy, H.; Myrback, K. (1960). "Other glucosidases". In Boyer, P.D. (ed.). The Enzymes. Vol. 4 (2nd ed.). New York: Academic Press. pp. 369–378.
^Sivikami, S.; Radhakrishnan, A.N. (1973). "Purification of rabbit intestinal glucoamylase by affinity chromatography on Sephadex G-200". Indian J. Biochem. Biophys. 10 (4): 283–284. PMID 4792946.
^"alpha-glucosidase activity Gene Ontology Term (GO:0090599)". www.informatics.jax.org. See: Definition, GO Tree View.
^"ENZYME - 3.2.1.20 alpha-glucosidase". enzyme.expasy.org. Group of enzymes whose specificity is directed mainly toward the exohydrolysis of 1,4-alpha-glucosidic linkages, and that hydrolyze oligosaccharides rapidly, relative to polysaccharides, which are hydrolyzed relatively slowly, or not at all.
^Tadera K, Minami Y, Takamatsu K, Matsuoka T (April 2006). "Inhibition of α-glucosidase and α-amylase by flavonoids". J. Nutr. Sci. Vitaminol. 52 (2): 149–53. doi:10.3177/jnsv.52.149. PMID 16802696.
^Hoefsloot L; M Hoogeveen-Westerveld; A J Reuser; B A Oostra (1 December 1990). "Characterization of the human lysosomal α-glucosidase gene". Biochem. J. 272 (2): 493–497. doi:10.1042/bj2720493. PMC1149727. PMID 2268276.
^Hermans, Monique; Marian Kroos; Jos Van Beeumen; Ben Oostra; Arnold Reuser (25 July 1991). "Human Lysosomal a-Glucosidase Characterization of The Catalytic Site". The Journal of Biological Chemistry. 21. 266 (21): 13507–13512. doi:10.1016/S0021-9258(18)92727-4. Retrieved 1 March 2012.
^Wu XQ, Xu H, Yue H, Liu KQ, Wang XY (December 2009). "Inhibition kinetics and the aggregation of α-glucosidase by different denaturants". Protein J. 28 (9–10): 448–56. doi:10.1007/s10930-009-9213-0. PMID 19921411. S2CID 36546023.
^"FDA Approves First Treatment for Pompe Disease". FDA News Release. FDA. Retrieved 1 March 2012.
^Yoshimizu, M.; Tajima, Y; Matsuzawa, F; Aikawa, S; Iwamoto, K; Kobayashi, T; Edmunds, T; Fujishima, K; Tsuji, D; Itoh, K; Ikekita, M; Kawashima, I; Sugawara, K; Ohyanagi, N; Suzuki, T; Togawa, T; Ohno, K; Sakuraba, H (May 2008). "Binding parameters and thermodynamics of the interaction of imino sugars with a recombinant human acid α-glucosidase (alglucosidase alfa): insight into the complex formation mechanism". Clin Chim Acta. 391 (1–2): 68–73. doi:10.1016/j.cca.2008.02.014. PMID 18328816.
^Bischoff H (August 1995). "The mechanism of α-glucosidase inhibition in the management of diabetes". Clin Invest Med. 18 (4): 303–11. PMID 8549017.
^Kim JS, Kwon CS, Son KH (November 2000). "Inhibition of α-glucosidase and amylase by luteolin, a flavonoid". Biosci. Biotechnol. Biochem. 64 (11): 2458–61. doi:10.1271/bbb.64.2458. PMID 11193416. S2CID 5757649.
^Zhen, et al. (November 2017). "Synthesis of novel flavonoid alkaloids as α-glucosidase inhibitors". Bioorganic & Medicinal Chemistry. 25 (20): 5355–64. doi:10.1016/j.bmc.2017.07.055. PMID 28797772.
^Mahmoud AM, Geslevich J, Kint J, et al. (March 1998). "Seminal plasma α-glucosidase activity and male infertility". Hum. Reprod. 13 (3): 591–5. doi:10.1093/humrep/13.3.591. PMID 9572418.
^Mehta, Anand; Zitzmann, Nicole; Rudd, Pauline M; Block, Timothy M; Dwek, Raymond A (23 June 1998). "α-Glucosidase inhibitors as potential broad based anti-viral agents". FEBS Letters. 430 (1–2): 17–22. doi:10.1016/S0014-5793(98)00525-0. PMID 9678587. S2CID 25156942.
glucosidase, been, suggested, that, maltase, merged, into, this, article, discuss, proposed, since, november, 2023, systematic, name, glucoside, glucohydrolase, glucosidase, located, brush, border, small, intestine, that, acts, upon, bonds, hexamer, sulfolobus. It has been suggested that Maltase be merged into this article Discuss Proposed since November 2023 a Glucosidase EC 3 2 1 20 systematic name a D glucoside glucohydrolase is a glucosidase located in the brush border of the small intestine that acts upon a 1 4 bonds 1 2 3 4 5 6 a Glucosidasea Glucosidase hexamer Sulfolobus solfataricusIdentifiersEC no 3 2 1 20CAS no 9001 42 7DatabasesIntEnzIntEnz viewBRENDABRENDA entryExPASyNiceZyme viewKEGGKEGG entryMetaCycmetabolic pathwayPRIAMprofilePDB structuresRCSB PDB PDBe PDBsumSearchPMCarticlesPubMedarticlesNCBIproteins Glycogen structure segment Maltose Hydrolysis of terminal non reducing 1 4 linked a D glucose residues with release of D glucose This is in contrast to EC 3 2 1 21 b glucosidase Contents 1 Terminology 1 1 GO 0090599 the broad sense 1 2 EC 3 2 1 20 the narrow sense 2 Mechanism 3 Structure 4 Disease relevance 5 See also 6 ReferencesTerminology editGO 0090599 the broad sense edit The Gene Ontology entry GO 0090599 represents the broad sense of alpha glucosidase It is defined as catalysis of the hydrolysis of terminal non reducing alpha linked alpha D glucose residue with release of alpha D glucose In this sense alpha glucosidase can encompass a wide range of enzyme activitiess differing by the linkage of their terminal 1 3 1 4 or 1 6 the specific identity of their substrate sucrose maltose or starch among other aspects 7 EC 3 2 1 20 the narrow sense edit The definition associated with Enzyme Commission number 3 2 1 20 is narrower It requires the linkage to be 1 4 and the preferred substrate to be smaller oligosaccharides as opposed to larger polysaccharides like starch alpha amylase would otherwise be included Human genes that produce enzymes with activities specified by this EC number include 8 MGAM is the maltase glucoamylase found on the intestine brush border GAA is the acid alpha glucosidase found in the lysosome GANC neutral alpha glucosidase C Synonyms mentioned by the Commission include maltase glucoinvertase glucosidosucrase maltase glucoamylase a glucopyranosidase glucosidoinvertase a D glucosidase a glucoside hydrolase a 1 4 glucosidase a D glucoside glucohydrolase 9 These names are not recommended because they may only refer to a specific activity of the enzyme or a specific protein having this acvitity Mechanism edita Glucosidase hydrolyzes terminal non reducing 1 4 linked a glucose residues to release a single a glucose molecule 10 a Glucosidase is a carbohydrate hydrolase that releases a glucose as opposed to b glucose b Glucose residues can be released by glucoamylase a functionally similar enzyme The substrate selectivity of a glucosidase is due to subsite affinities of the enzyme s active site 11 Two proposed mechanisms include a nucleophilic displacement and an oxocarbenium ion intermediate 11 nbsp Example of an a glucosidase catalyzed reaction maltotriose water a glucose Rhodnius prolixus a blood sucking insect forms hemozoin Hz during digestion of host hemoglobin Hemozoin synthesis is dependent on the substrate binding site of a glucosidase 12 Trout liver a glucosidases were extracted and characterized It was shown that for one of the trout liver a glucosidases maximum activity of the enzyme was increased by 80 during exercise in comparison to a resting trout This change was shown to correlate to an activity increase for liver glycogen phosphorylase It is proposed that a glucosidase in the glucosidic path plays an important part in complementing the phosphorolytic pathway in the liver s metabolic response to energy demands of exercise 13 Yeast and rat small intestinal a glucosidases have been shown to be inhibited by several groups of flavonoids 14 Structure edit nbsp a glucosidase in complex with maltose and NAD a Glucosidases can be divided according to primary structure into two families 11 The gene coding for human lysosomal a glucosidase is about 20 kb long and its structure has been cloned and confirmed 15 Human lysosomal a glucosidase has been studied for the significance of the Asp 518 and other residues in proximity of the enzyme s active site It was found that substituting Asp 513 with Glu 513 interferes with posttranslational modification and intracellular transport of a glucosidase s precursor Additionally the Trp 516 and Asp 518 residues have been deemed critical for the enzyme s catalytic functionality 16 Kinetic changes in a glucosidase have been shown to be induced by denaturants such as guanidinium chloride GdmCl and SDS solutions These denaturants cause loss of activity and conformational change A loss of enzyme activity occurs at much lower concentrations of denaturant than required for conformational changes This leads to a conclusion that the enzyme s active site conformation is less stable than the whole enzyme conformation in response to the two denaturants 17 Disease relevance editGlycogen storage disease type II also called Pompe disease a disorder in which a glucosidase is deficient In 2006 the drug alglucosidase alfa became the first released treatment for Pompe disease and acts as an analog to a glucosidase 18 Further studies of alglucosidase alfa revealed that iminosugars exhibit inhibition of the enzyme It was found that one compound molecule binds to a single enzyme molecule It was shown that 1 deoxynojirimycin DNJ would bind the strongest of the sugars tested and blocked the active site of the enzyme almost entirely The studies enhanced knowledge of the mechanism by which a glucosidase binds to imino sugars 19 Diabetes Acarbose an a glucosidase inhibitor competitively and reversibly inhibits a glucosidase in the intestines This inhibition lowers the rate of glucose absorption through delayed carbohydrate digestion and extended digestion time Acarbose may be able to prevent the development of diabetic symptoms 20 Hence a glucosidase inhibitors like acarbose are used as anti diabetic drugs in combination with other anti diabetic drugs Luteolin has been found to be a strong inhibitor of a glucosidase The compound can inhibit the enzyme up to 36 with a concentration of 0 5 mg ml 21 As of 2016 this substance is being tested in rats mice and cell culture Flavonoid analogues have been demonstrated with inhibition activity 22 Azoospermia Diagnosis of azoospermia has potential to be aided by measurement of a glucosidase activity in seminal plasma Activity in the seminal plasma corresponds to the functionality of the epididymis 23 Antiviral agents Many animal viruses possess an outer envelope composed of viral glycoproteins These are often required for the viral life cycle and utilize cellular machinery for synthesis Inhibitors of a glucosidase show that the enzyme is involved in the pathway for N glycans for viruses such as HIV and human hepatitis B virus HBV Inhibition of a glucosidase can prevent fusion of HIV and secretion of HBV 24 See also editAlglucosidase alfa Alpha glucosidase inhibitor Some other glucosidases Cellulase Beta glucosidase Glycogen debranching enzymeReferences edit alpha Glucosidases at the U S National Library of Medicine Medical Subject Headings MeSH Bruni C B Sica V Auricchio F Covelli I 1970 Further kinetic and structural characterization of the lysosomal a D glucoside glucohydrolase from cattle liver Biochim Biophys Acta 212 3 470 477 doi 10 1016 0005 2744 70 90253 6 PMID 5466143 Flanagan P R Forstner G G 1978 Purification of rat intestinal maltase glucoamylase and its anomalous dissociation either by heat or by low pH Biochem J 173 2 553 563 doi 10 1042 bj1730553 PMC 1185809 PMID 29602 Larner J Lardy H Myrback K 1960 Other glucosidases In Boyer P D ed The Enzymes Vol 4 2nd ed New York Academic Press pp 369 378 Sivikami S Radhakrishnan A N 1973 Purification of rabbit intestinal glucoamylase by affinity chromatography on Sephadex G 200 Indian J Biochem Biophys 10 4 283 284 PMID 4792946 Sorensen S H Noren O Sjostrom H Danielsen E M 1982 Amphiphilic pig intestinal microvillus maltase glucoamylase Structure and specificity Eur J Biochem 126 3 559 568 doi 10 1111 j 1432 1033 1982 tb06817 x PMID 6814909 alpha glucosidase activity Gene Ontology Term GO 0090599 www informatics jax org See Definition GO Tree View ENZYME 3 2 1 20 alpha glucosidase enzyme expasy org Group of enzymes whose specificity is directed mainly toward the exohydrolysis of 1 4 alpha glucosidic linkages and that hydrolyze oligosaccharides rapidly relative to polysaccharides which are hydrolyzed relatively slowly or not at all ExplorEnz EC 3 2 1 20 www enzyme database org EC 3 2 1 20 ExPASy Retrieved 1 March 2012 a b c Chiba S August 1997 Molecular mechanism in a glucosidase and glucoamylase Biosci Biotechnol Biochem 61 8 1233 9 doi 10 1271 bbb 61 1233 PMID 9301101 Mury FB da Silva JR Ferreira LS et al 2009 a Glucosidase promotes hemozoin formation in a blood sucking bug an evolutionary history PLOS ONE 4 9 e6966 Bibcode 2009PLoSO 4 6966M doi 10 1371 journal pone 0006966 PMC 2734994 PMID 19742319 Mehrani H Storey KB October 1993 Characterization of a glucosidases from rainbow trout liver Arch Biochem Biophys 306 1 188 94 doi 10 1006 abbi 1993 1499 PMID 8215402 Tadera K Minami Y Takamatsu K Matsuoka T April 2006 Inhibition of a glucosidase and a amylase by flavonoids J Nutr Sci Vitaminol 52 2 149 53 doi 10 3177 jnsv 52 149 PMID 16802696 Hoefsloot L M Hoogeveen Westerveld A J Reuser B A Oostra 1 December 1990 Characterization of the human lysosomal a glucosidase gene Biochem J 272 2 493 497 doi 10 1042 bj2720493 PMC 1149727 PMID 2268276 Hermans Monique Marian Kroos Jos Van Beeumen Ben Oostra Arnold Reuser 25 July 1991 Human Lysosomal a Glucosidase Characterization of The Catalytic Site The Journal of Biological Chemistry 21 266 21 13507 13512 doi 10 1016 S0021 9258 18 92727 4 Retrieved 1 March 2012 Wu XQ Xu H Yue H Liu KQ Wang XY December 2009 Inhibition kinetics and the aggregation of a glucosidase by different denaturants Protein J 28 9 10 448 56 doi 10 1007 s10930 009 9213 0 PMID 19921411 S2CID 36546023 FDA Approves First Treatment for Pompe Disease FDA News Release FDA Retrieved 1 March 2012 Yoshimizu M Tajima Y Matsuzawa F Aikawa S Iwamoto K Kobayashi T Edmunds T Fujishima K Tsuji D Itoh K Ikekita M Kawashima I Sugawara K Ohyanagi N Suzuki T Togawa T Ohno K Sakuraba H May 2008 Binding parameters and thermodynamics of the interaction of imino sugars with a recombinant human acid a glucosidase alglucosidase alfa insight into the complex formation mechanism Clin Chim Acta 391 1 2 68 73 doi 10 1016 j cca 2008 02 014 PMID 18328816 Bischoff H August 1995 The mechanism of a glucosidase inhibition in the management of diabetes Clin Invest Med 18 4 303 11 PMID 8549017 Kim JS Kwon CS Son KH November 2000 Inhibition of a glucosidase and amylase by luteolin a flavonoid Biosci Biotechnol Biochem 64 11 2458 61 doi 10 1271 bbb 64 2458 PMID 11193416 S2CID 5757649 Zhen et al November 2017 Synthesis of novel flavonoid alkaloids as a glucosidase inhibitors Bioorganic amp Medicinal Chemistry 25 20 5355 64 doi 10 1016 j bmc 2017 07 055 PMID 28797772 Mahmoud AM Geslevich J Kint J et al March 1998 Seminal plasma a glucosidase activity and male infertility Hum Reprod 13 3 591 5 doi 10 1093 humrep 13 3 591 PMID 9572418 Mehta Anand Zitzmann Nicole Rudd Pauline M Block Timothy M Dwek Raymond A 23 June 1998 a Glucosidase inhibitors as potential broad based anti viral agents FEBS Letters 430 1 2 17 22 doi 10 1016 S0014 5793 98 00525 0 PMID 9678587 S2CID 25156942 Portal nbsp Biology Retrieved from https en wikipedia org w index php title A Glucosidase amp oldid 1195447014, wikipedia, wiki, book, books, library,
