グリコーゲン脱分枝酵素

関: glycogen debranching enzyme system

WordNet

one form in which body fuel is stored; stored primarily in the liver and broken down into glucose when needed by the body (同)animal_starch
any of several complex proteins that are produced by cells and act as catalysts in specific biochemical reactions

PrepTutorEJDIC

グリコーゲン,糖原
酵素

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/04/11 18:39:31」(JST)

wiki en

[Wiki en表示]

Image of debranching enzyme in E. Coli

amylo-α-1,6-glucosidase

Identifiers

EC number

3.2.1.33

CAS number

9012-47-9

Databases

IntEnz

IntEnz view

BRENDA

BRENDA entry

ExPASy

NiceZyme view

KEGG

KEGG entry

MetaCyc

metabolic pathway

PRIAM

profile

PDB structures

RCSB PDB PDBe PDBsum

Gene Ontology

AmiGO / EGO

Search
PMC	articles
PubMed	articles
NCBI	proteins

A debranching enzyme is a molecule that helps facilitate the breakdown of glycogen, which serves as a store of glucose in the body, through glucosyltransferase and glucosidase activity. Together with phosphorylases, debranching enzymes mobilize glucose reserves from glycogen deposits in the muscles and liver. This constitutes a major source of energy reserves in most organisms. Glycogen breakdown is highly regulated in the body, especially in the liver, by various hormones including insulin and glucagon, to maintain a homeostatic balance of blood-glucose levels.^[3] When glycogen breakdown is compromised by mutations in the glycogen debranching enzyme, metabolic diseases such as Glycogen storage disease type III can result.^[4]^[5]

Glucosyltransferase and glucosidase are performed by a single enzyme in mammals, yeast, and some bacteria, but by two distinct enzymes in E. coli and other bacteria, complicating nomenclature. Proteins that catalyze both functions are referred to as glycogen debranching enzymes (GDEs). When glucosyltransferase and glucosidase are catalyzed by distinct enzymes, "glycogen debranching enzyme" usually refers to the glucosidase enzyme. In some literature, an enzyme capable only of glucosidase is referred to as a "debranching enzyme".^[6]

Function

Together with phosphorylase, glycogen debranching enzymes function in glycogen breakdown and glucose mobilization. When phosphorylase has digested a glycogen branch down to four glucose residues, it will not remove further residues. Glycogen debranching enzymes assist phosphorylase, the primary enzyme involved in glycogen breakdown, mobilize glycogen stores. Phosphorylase can only cleave α-1,4- glycosidic bond between adjacent glucose molecules in glycogen but branches exist as α-1,6 linkages. When phosphorylase reaches four residues from a branching point it stops cleaving; because 1 in 10 residues is branched, cleavage by phosphorylase alone would not be sufficient in mobilizing glycogen stores.^[7]^[8] Before phosphorylase can resume catabolism, debranching enzymes perform two functions:

4-α-D-glucanotransferase (EC 2.4.1.25), or glucosyltransferase, transfers three glucose residues from the four-residue glycogen branch to a nearby branch. This exposes a single glucose residue joined to the glucose chain through an α -1,6 glycosidic linkage^[7]
Amylo-α-1,6-glucosidase (EC 3.2.1.33), or glucosidase, cleaves the remaining alpha-1,6 linkage, producing glucose and a linear chain of glycogen.^[7] The mechanism by which the glucosidase cleaves the α -1,6-linkage is not fully known because the amino acids in the active site have not yet been identified. It is thought to proceed through a two step acid base assistance type mechanism, with an oxocarbenium ion intermediate, and retention of configuration in glucose.^[9] This is a common method through which to cleave bonds, with an acid below the site of hydrolysis to lend a proton and a base above to deprotinate a water which can then act as a nucleophile. These acids and bases are amino acid side chains in the active site of the enzyme. A scheme for the mechanism is shown in the figure below.^[10]

Thus the debranching enzymes, transferase and α-1,6- glucosidase converts the branched glycogen structure into a linear one, paving the way for further cleavage by phosphorylase.

Structure and activity

Two enzymes

In E. coli and other bacteria, glucosyltransferase and glucosidase functions are performed by two distinct enzymes. In E. coli, Glucose transfer is performed by 4-alpha-glucanotransferase, a 78.5 kDa protein coded for by the gene malQ.^[11] A second protein, referred to as debranching enzyme, performs α-1,6-glucose cleavage. This enzyme has a molecular mass of 73.6 kDa, and is coded for by the gene glgX.^[12] Activity of the two enzymes is not always necessarily coupled. In E. coli glgX selectively catalyzes the cleavage of 4-subunit branches, without the action of glucanotransferase. The product of this cleavage, maltotetraose, is further degraded by maltodextrin phosphorylase.^[4]^[13]

E. coli GlgX is structurally similar to the protein isoamylase. The monomeric protein contains a central domain in which eight parallel beta-strands are surrounded by eight parallel alpha strands. Notable within this structure is a groove 26 angstroms long and 9 angstroms wide, containing aromatic residues that are thought to stabilize a four-glucose branch before cleavage.^[4]

One enzyme with two catalytic sites

In mammals and yeast, a single enzyme performs both debranching functions.^[14] The human glycogen debranching enzyme (gene: AGL) is a monomer with a molecular weight of 175 kDa. It has been shown that the two catalytic actions of AGL can function independently of each other, demonstrating that multiple active sites are present. This idea has been reinforced with inhibitors of the active site, such as polyhydroxyamine, which were found to inhibit glucosidase activity while transferase activity was not measurably changed.^[15] Glycogen debranching enzyme is the only known eukaryotic enzyme that contains multiple catalytic sites and is active as a monomer.^[16]^[17]

Some studies have shown that the C-terminal half of yeast GDE is associated with glucosidase activity, while the N-terminal half is associated with glucosyltransferase activity.^[14] In addition to these two active sites, AGL appears to contain a third active site that allows it to bind to a glycogen polymer.^[18] Though the complete structure of the GDE in Eukaryotes is yet to be determined it is thought to bind to six glucose molecules of the chain as well as the branched glucose, thus corresponding to 7 subunits within the active site, as shown in the figure below.^[19]

It was seen that when glucose ‘a’, ‘b’, ‘c’ and ‘0’ in the active site was hydrolyzed the most rapidly.^[19] This indicated that this region of the glycogen chain bond strongest to the active site because a stronger interaction between enzyme and substrate leads to a more rapid hydrolysis.

Despite these advances, the complete structure of GDE in eukaryotes has yet to be determined.^[6] The glycogen-degrading enzyme of the archaea Sulfolobus solfataricus is better characterized than those of eukaryotes. The GDE of S. solfataricus is known as treX. Although, like mammalian GDE, treX has both amylosidase and glucanotransferase functions, TreX is structurally similar to glgX, and hass a mass of 80kD and one active site.^[6]^[20] Unlike either glgX or AGL, however, treX exists as a dimer and tetramer in solution. TreX's oligomeric form seems to play a significant role in altering both enzyme shape and function. Dimerization is thought to stabilize a "flexible loop" located close to the active site. This may be key to explaining why treX (and not glgX) shows glucosyltransferase activity. As a tetramer, the catalytic efficiency of treX is increased fourfold over its dimeric form.^[4]^[21]

Genetic Location

The official name for the gene is “amylo- α- 1,6- glucosidase, 4- α- glucanotransferase,” with the official symbol AGL. AGL is an autosomal gene found on chromosome lp21.^[8] The AGL gene provides instructions for making several different versions, known as isoforms, of the glycogen debranching enzyme. These isoforms vary by size and are expressed in different tissues, such as liver and muscle. This gene has been studied in great detail, because mutation at this gene is the cause of Glycogen Storage Disease Type III.^[22] The gene is 85 kb long, has 35 exons and encodes for a 7.0 kb- mRNA. Translation of the gene begins at exon 3,which encodes for the first 27 amino acids of the AGL gene, because the first two exons (68kb) contain the 5’ untranslated region. Exons 4-35 encode the remaining 1505 amino acids of the AGL gene.^[5] Studies produced by the department of pediatrics at Duke University suggest that the human AGL gene contains at minimum 2 promotor regions, sites where the transcription of the gene begins, that result in differential expression of isoform, different forms of the same protein, mRNAs in a manner that is specific for different tissues.^[18]^[23]

Clinical Significance

When GDE activity is compromised, the body cannot effectively release stored glycogen, type III Glycogen Storage Disease (debrancher deficiency), an autosomal recessive disorder, can result. In GSD III glycogen breakdown is incomplete and there is accumulation of abnormal glycogen with short outer branches.^[24]

Most patients exhibit GDE defiency in both liver and muscle (TypeIIIa), although 15% of patients have retained GDE in muscle while having it absent from the liver (Type IIIb).^[8] Depending on mutation location, different mutations in the AGL gene can affect different isoforms of the gene expression. For example, mutations that occur on exon 3, affect the form which affect the isoform that is primarily expressed in the liver; this would lead to GSD type III.^[25]

These different manifestation produce varied symptoms, which can be nearly indistinguishable from Type I GSD, including hepatomegaly, hypoglycemia in children, short stature, myopathy, and cardiomyopathy.^[5]^[26] Type IIIa patients often exhibit symptoms related to liver disease and progressive muscle involvement, with variations caused by age of onset, rate of disease progression and severity. Patients with Type IIIb generally symptoms related to liver disease.^[27] Type III patients be distinguished by elevated liver enzymes, with normal uric acid and blood lactate levels, differing from other forms of GSD.^[25] In patients with muscle involvement, Type IIIa, the muscle weakness becomes predominant into adulthood and can lead to ventricular hypertrophy and distal muscle wasting.^[25]

References

^ "Human PubMed Reference:".
^ "Mouse PubMed Reference:".
^ Hers HG, Verhue W, Van hoof F (October 1967). "The determination of amylo-1,6-glucosidase". Eur. J. Biochem. 2 (3): 257–64. doi:10.1111/j.1432-1033.1967.tb00133.x. PMID 6078537.
^ ^a ^b ^c ^d Song HN, Jung TY, Park JT, Park BC, Myung PK, Boos W, Woo EJ, Park KH (June 2010). "Structural rationale for the short branched substrate specificity of the glycogen debranching enzyme GlgX". Proteins. 78 (8): 1847–55. doi:10.1002/prot.22697. PMID 20187119.
^ ^a ^b ^c Bao Y, Dawson TL, Chen YT (December 1996). "Human glycogen debranching enzyme gene (AGL): complete structural organization and characterization of the 5' flanking region". Genomics. 38 (2): 155–65. doi:10.1006/geno.1996.0611. PMID 8954797.
^ ^a ^b ^c Woo EJ, Lee S, Cha H, Park JT, Yoon SM, Song HN, Park KH (October 2008). "Structural insight into the bifunctional mechanism of the glycogen-debranching enzyme TreX from the archaeon Sulfolobus solfataricus". J. Biol. Chem. 283 (42): 28641–8. doi:10.1074/jbc.M802560200. PMC 2661413. PMID 18703518.
^ ^a ^b ^c Stryer L, Berg JM, Tymoczko JL (2007). Biochemistry (6th ed.). San Francisco: W.H. Freeman. ISBN 0-7167-8724-5.
^ ^a ^b ^c Hondoh H, Saburi W, Mori H, et al. (May 2008). "Substrate recognition mechanism of alpha-1,6-glucosidic linkage hydrolyzing enzyme, dextran glucosidase from Streptococcus mutans". J. Mol. Biol. 378 (4): 913–22. doi:10.1016/j.jmb.2008.03.016. PMID 18395742.
^ Chiba S (August 1997). "Molecular mechanism in alpha-glucosidase and glucoamylase". Biosci. Biotechnol. Biochem. 61 (8): 1233–9. doi:10.1271/bbb.61.1233. PMID 9301101.
^ McCarter JD, Withers SG (December 1994). "Mechanisms of enzymatic glycoside hydrolysis". Curr. Opin. Struct. Biol. 4 (6): 885–92. doi:10.1016/0959-440X(94)90271-2. PMID 7712292.
^ "4-alpha-glucanotransferase - Escherichia coli (strain K12)".
^ "Glycogen debranching enzyme - Escherichia coli O139:H28 (strain E24377A / ETEC)". UniProt.
^ Dauvillée D, Kinderf IS, Li Z, Kosar-Hashemi B, Samuel MS, Rampling L, Ball S, Morell MK (February 2005). "Role of the Escherichia coli glgX gene in glycogen metabolism". J. Bacteriol. 187 (4): 1465–73. doi:10.1128/JB.187.4.1465-1473.2005. PMC 545640. PMID 15687211.
^ ^a ^b Nakayama A, Yamamoto K, Tabata S (August 2001). "Identification of the catalytic residues of bifunctional glycogen debranching enzyme". J. Biol. Chem. 276 (31): 28824–8. doi:10.1074/jbc.M102192200. PMID 11375985.
^ Gillard BK, White RC, Zingaro RA, Nelson TE (September 1980). "Amylo-1,6-glucosidase/4-alpha-glucanotransferase. Reaction of rabbit muscle debranching enzyme with an active site-directed irreversible inhibitor, 1-S-dimethylarsino-1-thio-beta-D-glucopyranoside". J. Biol. Chem. 255 (18): 8451–7. PMID 6447697.
^ Chen YT, He JK, Ding JH, Brown BI (December 1987). "Glycogen debranching enzyme: purification, antibody characterization, and immunoblot analyses of type III glycogen storage disease". Am. J. Hum. Genet. 41 (6): 1002–15. PMC 1684360. PMID 2961257.
^ "Glycogen debranching enzyme - Homo sapiens (Human)". UniProt.
^ ^a ^b Gillard BK, Nelson TE (September 1977). "Amylo-1,6-glucosidase/4-alpha-glucanotransferase: use of reversible substrate model inhibitors to study the binding and active sites of rabbit muscle debranching enzyme". Biochemistry. 16 (18): 3978–87. doi:10.1021/bi00637a007. PMID 269742.
^ ^a ^b Yamamoto E, Makino Y, Omichi K (May 2007). "Active site mapping of amylo-alpha-1,6-glucosidase in porcine liver glycogen debranching enzyme using fluorogenic 6-O-alpha-glucosyl-maltooligosaccharides". J. Biochem. 141 (5): 627–34. doi:10.1093/jb/mvm065. PMID 17317688.
^ "TreX - Actinoplanes sp. SN223/29". UniProt.
^ Park JT, Park HS, Kang HK, Hong JS, Cha H, Woo EJ, Kim JW, Kim MJ, Boos W, Lee S, Park KH (2008). "Oligomeric and functional properties of a debranching enzyme (TreX) from the archaeon Sulfobus solfataricus P2.". Biocatalysis and Biotransformation. 26: 76–85. doi:10.1080/10242420701806652.
^ "Genes (Genetic Home Reference a service of U.S. National Library of Medicine.". Retrieved February 29, 2012.
^ Ding JH, de Barsy T, Brown BI, Coleman RA, Chen YT (January 1990). "Immunoblot analyses of glycogen debranching enzyme in different subtypes of glycogen storage disease type III". J. Pediatr. 116 (1): 95–100. doi:10.1016/S0022-3476(05)81652-X. PMID 2295969.
^ Monga SP (2010). Molecular Pathology of Liver Diseases (Molecular Pathology Library). Berlin: Springer. ISBN 1-4419-7106-8.
^ ^a ^b ^c Shen J, Bao Y, Liu HM, Lee P, Leonard JV, Chen YT (July 1996). "Mutations in exon 3 of the glycogen debranching enzyme gene are associated with glycogen storage disease type III that is differentially expressed in liver and muscle". J. Clin. Invest. 98 (2): 352–7. doi:10.1172/JCI118799. PMC 507437. PMID 8755644.
^ Talente GM, Coleman RA, Alter C, Baker L, Brown BI, Cannon RA, et al. (February 1994). "Glycogen storage disease in adults". Ann. Intern. Med. 120 (3): 218–26. doi:10.7326/0003-4819-120-3-199402010-00008. PMID 8273986.
^ Kishnani PS, Austin SL, Arn P, Bali DS, Boney A, Case LE, et al. (July 2010). "Glycogen storage disease type III diagnosis and management guidelines". Genetics in Medicine. 12 (7): 446–63. doi:10.1097/GIM.0b013e3181e655b6. PMID 20631546.

External links

GeneReviews/NCBI/NIH/UW entry on Glycogen Storage Disease Type III
OMIM entries on Glycogen Storage Disease Type III
Glycogen debranching enzyme at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. グリコーゲン分枝酵素欠損症（糖原病IV型、アンダーセン病） glycogen branching enzyme deficiency glycogen storage disease iv andersen disease
2. 肝グリコーゲン合成酵素欠損症（糖原病0型） liver glycogen synthase deficiency glycogen storage disease 0
3. グルコースおよびグリコーゲン代謝の遺伝性疾患の概要 overview of inherited disorders of glucose and glycogen metabolism
4. グリコーゲン脱分枝酵素欠損症（糖原病III型） glycogen debrancher deficiency glycogen storage disease iii
5. Lysosomal acid alpha-glucosidase deficiency (Pompe disease, glycogen storage disease II, acid maltase deficiency)

English Journal

LC MS/MS identification of large structural proteins from bull muscle and their degradation products during post mortem storage.

Wu G1, Clerens S2, Farouk MM3.Author information 1AgResearch, Ruakura Research Centre, Hamilton, New Zealand. Electronic address: guojie.wu@agresearch.co.nz.2AgResearch, Lincoln Research Centre, Christchurch, New Zealand.3AgResearch, Ruakura Research Centre, Hamilton, New Zealand.AbstractLarge proteins (>100kDa) in bovine M. longissimus dorsi and their degradation products during post mortem ageing were investigated by gel electrophoresis and LC-MS/MS analysis. Seventeen protein bands from SDS-PAGE were analysed and 26 proteins were identified. Intact titin, nebulin and filamin were shown to break down during post mortem ageing of meat. A number of myosin super-family members were revealed on SDS-PAGE. Myosin heavy chain 1 (MYH1), myosin heavy chain 2 (MYH2), and myosin heavy chain 7 (MYH7) were distributed broadly across the bands in the forms of cross-linked/aggregated polymers, and also as fragments. Three myomesin family members: myomesin 1 (185kDa isoform 1), myomesin (M-protein) 2, 165kDa, and myomesin family member 3, were identified in the muscle samples. Several other proteins such as synemin, myosin binding protein C (C-protein), glycogen debranching enzyme and ryanodine receptor 2 were also identified.
Food chemistry.Food Chem.2014 May 1;150:137-44. doi: 10.1016/j.foodchem.2013.10.158. Epub 2013 Nov 2.
Large proteins (>100kDa) in bovine M. longissimus dorsi and their degradation products during post mortem ageing were investigated by gel electrophoresis and LC-MS/MS analysis. Seventeen protein bands from SDS-PAGE were analysed and 26 proteins were identified. Intact titin, nebulin and filamin w
PMID 24360430

Role in Tumor Growth of a Glycogen Debranching Enzyme Lost in Glycogen Storage Disease.

Guin S1, Pollard C, Ru Y, Ritterson Lew C, Duex JE, Dancik G, Owens C, Spencer A, Knight S, Holemon H, Gupta S, Hansel D, Hellerstein M, Lorkiewicz P, Lane AN, Fan TW, Theodorescu D.Author information 1Affiliations of authors: Department of Surgery (SGui, CP, YR, CRL, JED, GD, CO, DT) and Department of Pharmacology (SGui, CP, YR, CRL, JED, GD, CO, DT), University of Colorado, Denver, CO; Sigma-Aldrich Research Biotech, Saint Louis, MO (AS, SK, HH); Department of Pathology, Cleveland Clinic, Cleveland, OH (SGup, DH); Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley, CA (MH); Department of Medicine, University of California at San Francisco, San Francisco, CA (MH); Center for Regulatory and Environmental Analytical Metabolomics, Department of Chemistry, University of Louisville, Louisville, KY (PL); Graduate Center of Toxicology, Biopharm Complex, University of Kentucky, Lexington, KY (ANL, TW-MF); University of Colorado Comprehensive Cancer Center, Denver, CO (DT). Present affiliations: Department of Biomedical Informatics, Windber Research Institute, Windber, PA (YR); Mathematics and Computer Science Department, Eastern Connecticut State University, Willimantic, CT (GD).AbstractBACKGROUND: Bladder cancer is the most common malignancy of the urinary system, yet our molecular understanding of this disease is incomplete, hampering therapeutic advances.
Journal of the National Cancer Institute.J Natl Cancer Inst.2014 Apr 3. [Epub ahead of print]
BACKGROUND: Bladder cancer is the most common malignancy of the urinary system, yet our molecular understanding of this disease is incomplete, hampering therapeutic advances.METHODS: Here we used a genome-wide functional short-hairpin RNA (shRNA) screen to identify suppressors of in vivo bladder tum
PMID 24700805

Laforin-malin complex degrades polyglucosan bodies in concert with glycogen debranching enzyme and brain isoform glycogen phosphorylase.

Liu Y1, Zeng L, Ma K, Baba O, Zheng P, Liu Y, Wang Y.Author information 1Center for Cancer and Immunology Research, Children's National Medical Center and George Washington University, 111 Michigan Avenue NW, Washington, DC, 20010, USA, ynliu@childrensnational.org.AbstractIn Lafora disease (LD), the deficiency of either EPM2A or NHLRC1, the genes encoding the phosphatase laforin and E3 ligase, respectively, causes massive accumulation of less-branched glycogen inclusions, known as Lafora bodies, also called polyglucosan bodies (PBs), in several types of cells including neurons. The biochemical mechanism underlying the PB accumulation, however, remains undefined. We recently demonstrated that laforin is a phosphatase of muscle glycogen synthase (GS1) in PBs, and that laforin recruits malin, together reducing PBs. We show here that accomplishment of PB degradation requires a protein assembly consisting of at least four key enzymes: laforin and malin in a complex, and the glycogenolytic enzymes, glycogen debranching enzyme 1 (AGL1) and brain isoform glycogen phosphorylase (GPBB). Once GS1-synthesized polyglucosan accumulates into PBs, laforin recruits malin to the PBs where laforin dephosphorylates, and malin degrades the GS1 in concert with GPBB and AGL1, resulting in a breakdown of polyglucosan. Without fountional laforin-malin complex assembled on PBs, GPBB and AGL1 together are unable to efficiently breakdown polyglucosan. All these events take place on PBs and in cytoplasm. Deficiency of each of the four enzymes causes PB accumulation in the cytoplasm of affected cells. Demonstration of the molecular mechanisms underlying PB degradation lays a substantial biochemical foundation that may lead to understanding how PB metabolizes and why mutations of either EPM2A or NHLRC1 in humans cause LD. Mutations in AGL1 or GPBB may cause diseases related to PB accumulation.
Molecular neurobiology.Mol Neurobiol.2014 Apr;49(2):645-57. doi: 10.1007/s12035-013-8546-z. Epub 2013 Sep 26.
In Lafora disease (LD), the deficiency of either EPM2A or NHLRC1, the genes encoding the phosphatase laforin and E3 ligase, respectively, causes massive accumulation of less-branched glycogen inclusions, known as Lafora bodies, also called polyglucosan bodies (PBs), in several types of cells includi
PMID 24068615

Japanese Journal

Discrimination of porcine glycogen debranching enzyme isozymes by the ratios of their 4-α-glucanotransferase and amylo-α-1,6-glucosidase activities

Doi Seiko,Makino Yasushi,Omichi Kaoru
The journal of biochemistry 147(6), 851-856, 2010-06-01
NAID 10027876511

Novel AGL mutation in a Turkish patient with glycogen storage disease type IIIa

AOYAMA Yoshiko,ENDO Yoriko,EBARA Tetsu,MURASE Toshio,SHIN Yoon S.,PODSKARBI Teodor,OZER Isil,DEMIRKOL Mubeccel,GOKCAY Gulden,OKUBO Minoru
Pediatrics international : official journal of the Japan Pediatric Society 52(1), 145-147, 2010-02-01
NAID 10028181453

Inspection of the Activator Binding Site for 4-α-Glucanotransferase in Porcine Liver Glycogen Debranching Enzyme with Fluorogenic Dextrins

Yamamoto Eriko,Watanabe Yumiko,Makino Yasushi [他],OMICHI Kaoru
The journal of biochemistry 145(5), 585-590, 2009-05-01
NAID 10025588794

Related Pictures

★リンクテーブル★

関連記事	「debranching enzyme」「glycogen」

「debranching enzyme」

Search
PMC	articles
PubMed	articles
NCBI	proteins

4-α-glucanotransferase
Identifiers
EC number	2.4.1.25
CAS number	9032-09-1
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search
PMC	articles
PubMed	articles
NCBI	proteins

AGL
Identifiers
Aliases	AGL, GDE, amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase
External IDs	MGI: 1924809 HomoloGene: 536 GeneCards: AGL
Gene ontology
Molecular function	• transferase activity; • transferase activity, transferring glycosyl groups; • hydrolase activity, acting on glycosyl bonds; • protein binding; • catalytic activity; • hydrolase activity; • 4-alpha-glucanotransferase activity; • amylo-alpha-1,6-glucosidase activity; • glycogen debranching enzyme activity; • carbohydrate binding; • polysaccharide binding; • polyubiquitin binding;
Cellular component	• cytoplasm; • cytosol; • isoamylase complex; • extracellular region; • secretory granule lumen; • ficolin-1-rich granule lumen; • nucleus; • inclusion body; • sarcoplasmic reticulum;
Biological process	• glycogen biosynthetic process; • glycogen catabolic process; • metabolic process; • neutrophil degranulation; • glycogen metabolic process; • response to nutrient; • response to hormone; • response to glucocorticoid;
	Sources:Amigo / QuickGO
Orthologs
	178
	77559
	ENSG00000162688
	ENSMUSG00000033400
	P35573
	n/a
NM_000028; NM_000642; NM_000643; NM_000644; NM_000645;
	NM_000646
	NM_001081326
NP_000019; NP_000633; NP_000634; NP_000635; NP_000636;
	NP_000637
	n/a
	Wikidata
View/Edit Human	View/Edit Mouse

　　[★]

脱分枝酵素、枝切り酵素

「glycogen」

　　[★] グリコーゲン

[1] "Human PubMed Reference:".

[2] "Mouse PubMed Reference:".

[Hers-3] Hers HG, Verhue W, Van hoof F (October 1967). "The determination of amylo-1,6-glucosidase". Eur. J. Biochem. 2 (3): 257–64. doi:10.1111/j.1432-1033.1967.tb00133.x. PMID 6078537.

[Song-4] Song HN, Jung TY, Park JT, Park BC, Myung PK, Boos W, Woo EJ, Park KH (June 2010). "Structural rationale for the short branched substrate specificity of the glycogen debranching enzyme GlgX". Proteins. 78 (8): 1847–55. doi:10.1002/prot.22697. PMID 20187119.

[Bao-5] Bao Y, Dawson TL, Chen YT (December 1996). "Human glycogen debranching enzyme gene (AGL): complete structural organization and characterization of the 5' flanking region". Genomics. 38 (2): 155–65. doi:10.1006/geno.1996.0611. PMID 8954797.

[Woo-6] Woo EJ, Lee S, Cha H, Park JT, Yoon SM, Song HN, Park KH (October 2008). "Structural insight into the bifunctional mechanism of the glycogen-debranching enzyme TreX from the archaeon Sulfolobus solfataricus". J. Biol. Chem. 283 (42): 28641–8. doi:10.1074/jbc.M802560200. PMC 2661413. PMID 18703518.

[Berg-7] Stryer L, Berg JM, Tymoczko JL (2007). Biochemistry (6th ed.). San Francisco: W.H. Freeman. ISBN 0-7167-8724-5.

[Hondoh-8] Hondoh H, Saburi W, Mori H, et al. (May 2008). "Substrate recognition mechanism of alpha-1,6-glucosidic linkage hydrolyzing enzyme, dextran glucosidase from Streptococcus mutans". J. Mol. Biol. 378 (4): 913–22. doi:10.1016/j.jmb.2008.03.016. PMID 18395742.

[Molecule-9] Chiba S (August 1997). "Molecular mechanism in alpha-glucosidase and glucoamylase". Biosci. Biotechnol. Biochem. 61 (8): 1233–9. doi:10.1271/bbb.61.1233. PMID 9301101.

[MCCarter-10] McCarter JD, Withers SG (December 1994). "Mechanisms of enzymatic glycoside hydrolysis". Curr. Opin. Struct. Biol. 4 (6): 885–92. doi:10.1016/0959-440X(94)90271-2. PMID 7712292.

[UniProt_P15977-11] "4-alpha-glucanotransferase - Escherichia coli (strain K12)".

[UniProt_A7ZSW4-12] "Glycogen debranching enzyme - Escherichia coli O139:H28 (strain E24377A / ETEC)". UniProt.

[Dauvill.C3.A9e-13] Dauvillée D, Kinderf IS, Li Z, Kosar-Hashemi B, Samuel MS, Rampling L, Ball S, Morell MK (February 2005). "Role of the Escherichia coli glgX gene in glycogen metabolism". J. Bacteriol. 187 (4): 1465–73. doi:10.1128/JB.187.4.1465-1473.2005. PMC 545640. PMID 15687211.

[Nakayama-14] Nakayama A, Yamamoto K, Tabata S (August 2001). "Identification of the catalytic residues of bifunctional glycogen debranching enzyme". J. Biol. Chem. 276 (31): 28824–8. doi:10.1074/jbc.M102192200. PMID 11375985.

[Gillard_80-15] Gillard BK, White RC, Zingaro RA, Nelson TE (September 1980). "Amylo-1,6-glucosidase/4-alpha-glucanotransferase. Reaction of rabbit muscle debranching enzyme with an active site-directed irreversible inhibitor, 1-S-dimethylarsino-1-thio-beta-D-glucopyranoside". J. Biol. Chem. 255 (18): 8451–7. PMID 6447697.

[Chen-16] Chen YT, He JK, Ding JH, Brown BI (December 1987). "Glycogen debranching enzyme: purification, antibody characterization, and immunoblot analyses of type III glycogen storage disease". Am. J. Hum. Genet. 41 (6): 1002–15. PMC 1684360. PMID 2961257.

[UniProt_P35573-17] "Glycogen debranching enzyme - Homo sapiens (Human)". UniProt.

[Gillard-18] Gillard BK, Nelson TE (September 1977). "Amylo-1,6-glucosidase/4-alpha-glucanotransferase: use of reversible substrate model inhibitors to study the binding and active sites of rabbit muscle debranching enzyme". Biochemistry. 16 (18): 3978–87. doi:10.1021/bi00637a007. PMID 269742.

[Yamamoto-19] Yamamoto E, Makino Y, Omichi K (May 2007). "Active site mapping of amylo-alpha-1,6-glucosidase in porcine liver glycogen debranching enzyme using fluorogenic 6-O-alpha-glucosyl-maltooligosaccharides". J. Biochem. 141 (5): 627–34. doi:10.1093/jb/mvm065. PMID 17317688.

[UniProt_A8QX06-20] "TreX - Actinoplanes sp. SN223/29". UniProt.

[Park-21] Park JT, Park HS, Kang HK, Hong JS, Cha H, Woo EJ, Kim JW, Kim MJ, Boos W, Lee S, Park KH (2008). "Oligomeric and functional properties of a debranching enzyme (TreX) from the archaeon Sulfobus solfataricus P2.". Biocatalysis and Biotransformation. 26: 76–85. doi:10.1080/10242420701806652.

[Gene-22] "Genes (Genetic Home Reference a service of U.S. National Library of Medicine.". Retrieved February 29, 2012.

[Ding-23] Ding JH, de Barsy T, Brown BI, Coleman RA, Chen YT (January 1990). "Immunoblot analyses of glycogen debranching enzyme in different subtypes of glycogen storage disease type III". J. Pediatr. 116 (1): 95–100. doi:10.1016/S0022-3476(05)81652-X. PMID 2295969.

[Monga-24] Monga SP (2010). Molecular Pathology of Liver Diseases (Molecular Pathology Library). Berlin: Springer. ISBN 1-4419-7106-8.

[Shen-25] Shen J, Bao Y, Liu HM, Lee P, Leonard JV, Chen YT (July 1996). "Mutations in exon 3 of the glycogen debranching enzyme gene are associated with glycogen storage disease type III that is differentially expressed in liver and muscle". J. Clin. Invest. 98 (2): 352–7. doi:10.1172/JCI118799. PMC 507437. PMID 8755644.

[Talente-26] Talente GM, Coleman RA, Alter C, Baker L, Brown BI, Cannon RA, et al. (February 1994). "Glycogen storage disease in adults". Ann. Intern. Med. 120 (3): 218–26. doi:10.7326/0003-4819-120-3-199402010-00008. PMID 8273986.

[Kishnan-27] Kishnani PS, Austin SL, Arn P, Bali DS, Boney A, Case LE, et al. (July 2010). "Glycogen storage disease type III diagnosis and management guidelines". Genetics in Medicine. 12 (7): 446–63. doi:10.1097/GIM.0b013e3181e655b6. PMID 20631546.

v t e Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

匿名

検索

案内

案内

glycogen debranching enzyme