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{{Short description|Mammalian protein found in Homo sapiens}}
[[Image:Glycogen Debranching Enzyme.png|thumb|Image of debranching enzyme in E. Coli]]
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox_gene}}
The '''glycogen debranching enzyme''', in humans, is the protein encoded by the [[gene]] ''AGL''.<ref name=Gene/> This enzyme is essential for the [[Glycogenolysis|breakdown]] of [[glycogen]], which serves as a store of glucose in the body. It has separate glucosyltransferase and glucosidase activities.<ref name="Song"/><ref name="Bao"/>
{{enzyme
| Name = [[4-alpha-glucanotransferase|4-α-glucanotransferase]]
| image =
| width =
| caption =
| EC_number = 2.4.1.25
| CAS_number = 9032-09-1
| IUBMB_EC_number = 2/4/1/25
| GO_code = 0004134
}}
{{enzyme
| Name = amylo-α-1,6-glucosidase
| EC_number = 3.2.1.33
| CAS_number = 9012-47-9
| IUBMB_EC_number = 3/2/1/33
| GO_code = 0004135
| image =
| width =
| caption =
}}
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 [[phosphorylase]]s, 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.<ref name="Hers"/> When glycogen breakdown is compromised by mutations in the glycogen debranching enzyme, metabolic diseases such as [[Glycogen storage disease type III]] can result.<ref name="Song"/><ref name="Bao"/>
 
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 [[phosphorylase]]s, debranchingthe enzymesenzyme 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.<ref name="Hers"/> When glycogen breakdown is compromised by mutations in the glycogen debranching enzyme, metabolic diseases such as [[Glycogen storage disease type III]] can result.<ref name="Song"/><ref name="Bao"/>
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".<ref name=Woo/>
 
GlucosyltransferaseThe two steps of glycogen breakdown, 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"''.<ref name=Woo/>
 
== Function ==
 
Together with [[phosphorylase]], glycogen debranching enzymes function in [[glycogenolysis|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 [[Glycogenolysis|glycogen breakdown]], mobilizein the mobilization of glycogen stores. Phosphorylase can only cleave α-1,4- glycosidic bond between adjacent glucose molecules in glycogen but branches also 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.<ref name=Berg/><ref name=Hondoh/> Before phosphorylase can resume catabolism, debranching enzymes perform two functions:
* 4-α-D-glucanotransferase ({{EC number|2.4.1.25}}), or [[glucosyltransferase]], transfers three glucose [[residue (chemistry)|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<ref name="Berg"/>
* [[File:Glycosidase mechanism.png|thumb|Mechanism for cleaving of alpha-1,6 linkage.]]Amylo-α-1,6-glucosidase ({{EC number|3.2.1.33}}), or [[glucosidase]], cleaves the remaining alpha-1,6 linkage, producing glucose and a linear chain of glycogen.<ref name=Berg/> 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.<ref name=Molecule/> 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.<ref name=MCCarter/>
 
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.
* 4-α-D-glucanotransferase ({{EC number|2.4.1.25}}), or [[glucosyltransferase]], transfers three glucose [[residue (chemistry)|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<ref name="Berg"/>
* Amylo-α-1,6-glucosidase ({{EC number|3.2.1.33}}), or [[glucosidase]], cleaves the remaining alpha-1,6 linkage, producing glucose and a linear chain of glycogen.<ref name=Berg/> 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.<ref name=Molecule/> 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.<ref name=MCCarter/>
 
{|class=wikitable
[[File:Glycosidase mechanism.png]]
|{{infobox enzyme
 
| Name = [[4-alpha-glucanotransferase|4-α-glucanotransferase]]
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.
| image = =
| width =
| caption =
| EC_number = 2.4.1.25
| CAS_number = 9032-09-1
| GO_code = 0004134
}}
|{{infobox enzyme
| Name = amylo-α-1,6-glucosidase
| EC_number = 3.2.1.33
| CAS_number = 9012-47-9
| GO_code = 0004135
| image = =
| width =
| caption =
}}
|}
 
== Structure and activity ==
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=== Two enzymes ===
 
In ''[[Escherichia coli|E. coli]]'' and other bacteria, glucosyltransferase and glucosidase functions are performed by two distinct enzymesproteins. In ''E. coli'', Glucose transfer is performed by 4-alpha-glucanotransferase, a 78.5 kDa protein coded for by the gene malQ.<ref name="UniProt P15977"/> 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.<ref name="UniProt A7ZSW4"/> 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.<ref name=Song/><ref name="Dauvillée"/>
 
''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.<ref name=Song/>
 
Despite these advances, the complete structure of GDE in eukaryotes has yet to be determined.<ref name="Woo"/> The glycogen-degrading enzyme of the [[archaea]] ''[[Sulfolobus solfataricus]]'', istreX, betterprovides characterizedan thaninteresting thoseexample of [[eukaryotes]].using Thea GDEsingle ofactive ''S.site solfataricus''for is knowntwo as treX. Although, like mammalian GDE, treX has bothactivities: amylosidase and glucanotransferase functions,activities. TreX is structurally similar to glgX, and hasshas a mass of 80kD and one active site.<ref name="Woo" /><ref name ="UniProt A8QX06" /> 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.<ref name="Song" /><ref name="Park" />
 
=== One enzyme with two catalytic sites ===
In mammals and [[yeast]], a single enzyme performs both debranching functions.<ref name="Nakayama"/> 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.<ref name=Gillard_80/> Glycogen debranching enzyme is the only known eukaryotic enzyme that contains multiple catalytic sites and is active as a monomer.<ref name="Chen"/><ref name="UniProt P35573"/>
 
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.<ref name=Nakayama/> In addition to these two [[active site]]s, AGL appears to contain a third active site that allows it to bind to a glycogen polymer.<ref name="Gillard"/> Though the complete structure of the GDE in Eukaryotes is yet to be determined itIt 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.<ref name = Yamamoto/>
 
[[File:Hypothesized substraight binding ___location.png|thumb|center|Hypothesized sidechain binding sites|600px]]
 
The structure of the ''Candida glabrata'' GDE has been reported.<ref>{{cite journal | vauthors = Zhai L, Feng L, Xia L, Yin H, Xiang S | title = Crystal structure of glycogen debranching enzyme and insights into its catalysis and disease-causing mutations | journal = Nature Communications | volume = 7 | article-number = 11229 | date = April 2016 | pmid = 27088557 | pmc = 4837477 | doi = 10.1038/ncomms11229 | bibcode = 2016NatCo...711229Z }}</ref> The structure revealed that distinct domains in GDE encode the glucanotransferase and glucosidase activities. Their catalyses are similar to that of alpha-amylase and glucoamylase, respectively. Their active sites are selective towards the respective substrates, ensuring proper activation of GDE. Besides the active sites GDE have additional binding sites for glycogen, which are important for its recruitment to glycogen. Mapping the disease-causing mutations onto the GDE structure provided insights into glycogen storage disease type III.
It was seen that when glucose ‘a’, ‘b’, ‘c’ and ‘0’ in the [[active site]] was hydrolyzed the most rapidly.<ref name=Yamamoto/> 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.
 
== Genetic Location___location ==
Despite these advances, the complete structure of GDE in eukaryotes has yet to be determined.<ref name="Woo"/> 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.<ref name=Woo/><ref name ="UniProt A8QX06"/> 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.<ref name=Song/><ref name="Park"/>
 
The official name for the gene is “amylo"amylo- α- 1,6- glucosidase, 4- α- glucanotransferase", with the official symbol AGL. AGL is an autosomal gene found on chromosome lp211p21.<ref name=Hondoh/> 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.<ref name=Gene/>
== Genetic Location ==
The gene is 85 kb long, has 35 [[exon]]s 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 5’5' untranslated region. Exons 4-35 encode the remaining 1505 amino acids of the AGL gene.<ref name= Bao/>
 
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.<ref name=Hondoh/> 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.<ref name=Gene/>
The gene is 85 kb long, has 35 [[exon]]s 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.<ref name= Bao/>
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.<ref name = Gillard /><ref name=Ding />
 
== Clinical Significancesignificance ==
{{Main|Glycogen storage disease type III}}
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.<ref name= Monga/>
 
Most patients exhibit GDE defiency in both liver and muscle (TypeIIIaType IIIa), although 15% of patients have retained GDE in muscle while having it absent from the liver (Type IIIb).<ref name=Hondoh/> 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.<ref name=Shen/>
 
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]].<ref name=Bao/><ref name=Talente/> 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.<ref name =Kishnan/> Type III patients be distinguished by elevated liver enzymes, with normal [[uric acid]] and blood lactate levels, differing from other forms of GSD.<ref name=Shen/> In patients with muscle involvement, Type IIIa, the muscle weakness becomes predominant into adulthood and can lead to ventricular [[hypertrophy]] and distal muscle wasting.<ref name=Shen/>
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{{Reflist | colwidth = 35em | refs =
 
<ref name="Song">{{cite journal | vauthors = Song HN, Jung TY, Park JT, Park BC, Myung PK, Boos W, Woo EJ, Park KH | title = Structural rationale for the short branched substrate specificity of the glycogen debranching enzyme GlgX | journal = Proteins | volume = 78 | issue = 8 | pages = 1847–551847–1855 | date = June 2010 | pmid = 20187119 | doi = 10.1002/prot.22697 | url = | issns2cid = 28334066 }}</ref>
 
<ref name="Bao">{{cite journal | vauthors = Bao Y, Dawson TL, Chen YT | title = Human glycogen debranching enzyme gene (AGL): complete structural organization and characterization of the 5' flanking region | journal = Genomics | volume = 38 | issue = 2 | pages = 155–165 | date = December 1996 | pmid = 8954797 | doi = 10.1006/geno.1996.0611 }}</ref>
 
<ref name="BaoBerg">{{cite journalbook | vauthors =Bao YStryer L, DawsonBerg TLJM, ChenTymoczko YTJL | title = Human glycogen debranching enzyme gene (AGL): complete structural organization and characterization of the 5' flanking regionBiochemistry | journaledition = Genomics6th | volumepublisher = 38W.H. | issue = 2Freeman | pages___location = 155–65San |date=December 1996Francisco | pmidyear = 89547972007 | doiisbn = 10.1006/geno.1996.0611| url = | issn =978-0-7167-8724-2 }}</ref>
 
<ref name="BergDauvillée">{{cite bookjournal |author1 vauthors =Stryer Dauvillée D, LubertKinderf |author2=BergIS, JeremyLi Mark |author3=TymoczkoZ, JohnKosar-Hashemi L.B, |Samuel titleMS, =Rampling BiochemistryL, |Ball editionS, =Morell 6thMK | languagetitle = |Role publisherof =the W.H.Escherichia Freemancoli |glgX ___locationgene =in Sanglycogen Franciscometabolism | yearjournal = 2007Journal |of origyear =Bacteriology | pagesvolume = 187 | quoteissue = 4 | isbnpages = 0-7167-8724-51465–1473 | oclcdate = February 2005 | doipmid = 15687211 | urlpmc = 545640 | accessdatedoi = 10.1128/JB.187.4.1465-1473.2005 }}</ref>
 
<ref name="DauvilléeNakayama">{{cite journal | vauthors =Dauvillée D, Kinderf IS, Li Z, Kosar-Hashemi B, SamuelNakayama MSA, RamplingYamamoto LK, BallTabata S, Morell MK | title = RoleIdentification of the Escherichiacatalytic coliresidues glgXof gene inbifunctional glycogen metabolismdebranching enzyme | journal = J.The Bacteriol.Journal of Biological Chemistry | volume = 187276 | issue = 431 | pages = 1465–7328824–28828 | date =February 2005August 2001 | pmid = 15687211 | pmc = 54564011375985 | doi = 10.11281074/JBjbc.187.4.1465-1473.2005M102192200 | urldoi-access = | issn =free }}</ref>
 
<ref name="NakayamaChen">{{cite journal | vauthors =Nakayama AChen YT, He JK, YamamotoDing KJH, TabataBrown SBI | title = IdentificationGlycogen ofdebranching theenzyme: catalyticpurification, residuesantibody characterization, and immunoblot analyses of bifunctionaltype III glycogen debranchingstorage enzymedisease | journal = J.American Biol.Journal Chem.of Human Genetics | volume = 27641 | issue = 316 | pages = 28824–81002–1015 | date =August 2001December 1987 | pmid = 113759852961257 | doipmc = 10.1074/jbc.M102192200 | url = | issn =1684360 }}</ref>
 
<ref name="ChenUniProt P35573">{{cite journalweb |vauthors=Chen YT,url He= JK, Ding JH, Brown BIhttps://www.uniprot.org/uniprot/P35573 | title = Glycogen debranching enzyme: purification,- antibodyHomo characterization,sapiens and immunoblot analyses of type III glycogen storage disease(Human) | journalpublisher = Am. J. Hum. Genet. | volume = 41 | issue = 6 | pages = 1002–15 |date=December 1987 | pmid = 2961257 | pmc = 1684360 | doi = | url = | issn =UniProt }}</ref>
 
<ref name="UniProt P35573Gillard_80">{{cite webjournal | urlvauthors = http://www.uniprot.org/uniprot/P35573Gillard BK, White RC, Zingaro RA, Nelson TE | title = GlycogenAmylo-1,6-glucosidase/4-alpha-glucanotransferase. Reaction of rabbit muscle debranching enzyme with an active site-directed Homoirreversible sapiensinhibitor, (Human)1-S-dimethylarsino-1-thio-beta-D-glucopyranoside | datejournal = |The formatJournal =of Biological Chemistry | workvolume = 255 | publisherissue = UniProt18 | pages = 8451–8457 | languagedate = |September archiveurl =1980 | archivedatepmid = 6447697 | quotedoi = 10.1016/S0021-9258(18)43517-X | accessdatedoi-access = free }}</ref>
 
<ref name="Gillard_80Gillard">{{cite journal | vauthors = Gillard BK, White RC, Zingaro RA, Nelson TE | title = Amylo-1,6-glucosidase/4-alpha-glucanotransferase.: Reactionuse of rabbitreversible musclesubstrate debranchingmodel enzymeinhibitors withto anstudy the binding and active site-directedsites irreversibleof inhibitor,rabbit 1-S-dimethylarsino-1-thio-beta-D-glucopyranosidemuscle debranching enzyme | journal = J. Biol. Chem.Biochemistry | volume = 25516 | issue = 18 | pages = 8451–73978–3987 | date = September 19801977 | pmid = 6447697269742 | doi = | url = | issn =10.1021/bi00637a007 }}</ref>
 
<ref name="GillardWoo">{{cite journal | vauthors =Gillard BKWoo EJ, NelsonLee TES, |Cha titleH, =Park Amylo-1JT,6-glucosidase/4-alpha-glucanotransferase: useYoon ofSM, reversibleSong substrateHN, modelPark inhibitorsKH to| studytitle the= bindingStructural andinsight activeinto sitesthe ofbifunctional rabbitmechanism muscleof the glycogen-debranching enzyme TreX from the archaeon Sulfolobus solfataricus | journal = BiochemistryThe Journal of Biological Chemistry | volume = 16283 | issue = 1842 | pages = 3978–8728641–28648 | date =September 1977October 2008 | pmid = 26974218703518 | pmc = 2661413 | doi = 10.10211074/bi00637a007jbc.M802560200 | doi-access = free }}</ref>
 
<ref name="UniProt A8QX06">{{cite web | url = https://www.uniprot.org/uniprot/A8QX06 | title = TreX - Actinoplanes sp. SN223/29 | publisher = UniProt }}</ref>
<ref name="Woo">{{cite journal |vauthors=Woo EJ, Lee S, Cha H, Park JT, Yoon SM, Song HN, Park KH | title = Structural insight into the bifunctional mechanism of the glycogen-debranching enzyme TreX from the archaeon Sulfolobus solfataricus | journal = J. Biol. Chem. | volume = 283 | issue = 42 | pages = 28641–8 |date=October 2008 | pmid = 18703518 | pmc = 2661413 | doi = 10.1074/jbc.M802560200 | url = | issn = }}</ref>
 
<ref name="UniProt A8QX06A7ZSW4">{{cite web | url = httphttps://www.uniprot.org/uniprot/A8QX06A7ZSW4 | title = TreXGlycogen -debranching Actinoplanesenzyme sp.- SN223/29Escherichia |coli dateO139:H28 =(strain |E24377A format/ = | work =ETEC) | publisher = UniProt | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = }}</ref>
 
<ref name="UniProt A7ZSW4P15977">{{cite web | url = httphttps://www.uniprot.org/uniprot/A7ZSW4P15977 | title = Glycogen debranching enzyme4-alpha-glucanotransferase - Escherichia coli O139:H28 (strain E24377A / ETECK12) | date = | format = | work = | publisher = UniProt | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = }}</ref>
 
<ref name="WooPark">{{cite journal |vauthors=WooPark EJJT, LeePark SHS, Kang HK, Hong JS, Cha H, ParkWoo JTEJ, YoonKim SMJW, SongKim HNMJ, Boos W, Lee S, Park KH | title = StructuralOligomeric insightand intofunctional the bifunctional mechanismproperties of thea glycogen-debranching enzyme (TreX) from the archaeon SulfolobusSulfobus solfataricus P2. | journal = J.Biocatalysis Biol.and Chem.Biotransformation | volumeyear = 2832008 | issuevolume = 4226 | pagesissue = 28641–81–2 |date=October 2008 | pmidpages = 18703518 | pmc = 266141376–85 | doi = 10.10741080/jbc.M80256020010242420701806652 | urls2cid = | issn =83831481 }}</ref>
<ref name="UniProt P15977">{{cite web | url = http://www.uniprot.org/uniprot/P15977 | title = 4-alpha-glucanotransferase - Escherichia coli (strain K12) | date = | format = | work = | publisher = | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = }}</ref>
 
<ref name="ParkTalente">{{cite journal | vauthors =Park JTTalente GM, ParkColeman HSRA, KangAlter HKC, HongBaker JSL, ChaBrown HBI, WooCannon EJRA, KimChen JWYT, KimCrigler MJJF, BoosFerreira WP, LeeHaworth SJC, ParkHerman KHGE, |Issenman titleRM, =Keating OligomericJP, andLinde functionalR, propertiesRoe ofTF, aSenior debranchingB, enzymeWolfsdorf (TreX)JI from| thetitle archaeon= SulfobusGlycogen solfataricusstorage P2.disease in adults | journal = BiocatalysisAnnals andof BiotransformationInternal Medicine | yearvolume = 2008120 | volumeissue = 263 | pages = 76–85218–226 | date = February 1994 | pmid = 8273986 | doi = 10.10807326/102424207018066520003-4819-120-3-199402010-00008 | s2cid = 24896145 }}</ref>
 
<ref name="Monga">{{cite book | vauthors = Monga SP | title = Molecular Pathology of Liver Diseases (Molecular Pathology Library) | publisher = Springer | ___location = Berlin | year = 2010 | isbn = 978-1-4419-7106-7 }}</ref>
<ref name="Talente">{{cite journal |vauthors=Talente GM, Coleman RA, Alter C, Baker L, Brown BI, Cannon RA, Chen YT, Crigler JF, Ferreira P, Haworth JC, Herman GE, Issenman RM, Keating JP, Linde R, Roe TF, Senior B, Wolfsdorf JI | title = Glycogen storage disease in adults | journal = Ann. Intern. Med. | volume = 120 | issue = 3 | pages = 218–26 |date=February 1994 | pmid = 8273986 | doi = 10.7326/0003-4819-120-3-199402010-00008| url = | issn = }}</ref>
 
<ref name="MongaHondoh">{{cite bookjournal | authorvauthors = SatdarshanHondoh P.H, S.Saburi W, Mori H, Okuyama M, Nakada T, Matsuura Y, Kimura MongaA | title = MolecularSubstrate Pathologyrecognition mechanism of Liveralpha-1,6-glucosidic Diseaseslinkage (Molecularhydrolyzing Pathologyenzyme, Library)dextran glucosidase from Streptococcus mutans | publisherjournal = SpringerJournal of Molecular Biology | ___locationvolume = Berlin378 | yearissue = 20104 | pages = 913–922 | isbndate = 1-4419-7106-8May 2008 | pmid = 18395742 | doi = 10.1016/j.jmb.2008.03.016 }}</ref>
 
<ref name="HondohMCCarter">{{cite journal | |vauthors =Hondoh H,McCarter Saburi WJD, MoriWithers H, etalSG | title = Substrate recognition mechanismMechanisms of alpha-1,6-glucosidicenzymatic linkageglycoside hydrolyzing enzyme, dextran glucosidase from Streptococcus mutanshydrolysis | journal = J.Current Mol.Opinion Biol.in Structural Biology | volume = 3784 | issue = 46 | pages = 913–22885–892 | date =May 2008December 1994 | pmid = 183957427712292 | doi = 10.1016/j.jmb.2008.03.0160959-440X(94)90271-2 }}</ref>
 
<ref name="MCCarterYamamoto">{{cite journal | vauthors =McCarter JDYamamoto E, Makino Y, WithersOmichi SGK | title = MechanismsActive site mapping of enzymaticamylo-alpha-1,6-glucosidase glycosidein hydrolysisporcine liver glycogen debranching enzyme using fluorogenic 6-O-alpha-glucosyl-maltooligosaccharides | journal = Curr.Journal Opin.of Struct. Biol.Biochemistry | volume = 4141 | issue = 65 | pages = 885–92627–634 | date =December 1994May 2007 | pmid = 771229217317688 | doi = 10.10161093/0959-440X(94)90271-2jb/mvm065 | urldoi-access = free }}</ref>
 
<ref name="YamamotoHers">{{cite journal | vauthors =Yamamoto EHers HG, MakinoVerhue YW, OmichiVan Khoof F | title = Active siteThe mappingdetermination of amylo-alpha-1,6-glucosidase in porcine liver glycogen debranching enzyme using fluorogenic 6-O-alpha-glucosyl-maltooligosaccharides | journal = J.European Biochem.Journal of Biochemistry | volume = 1412 | issue = 53 | pages = 627–34257–264 | date =May 2007October 1967 | pmid = 173176886078537 | doi = 10.10931111/jb/mvm065j.1432-1033.1967.tb00133.x }}</ref>
 
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<ref name="DingMolecule">{{cite journal | vauthors =Ding JH, de Barsy T, Brown BI, Coleman RA, ChenChiba YTS | title = ImmunoblotMolecular analyses of glycogen debranching enzymemechanism in different subtypes of glycogen storage diseasealpha-glucosidase typeand IIIglucoamylase | journal = J.Bioscience, Pediatr.Biotechnology, and Biochemistry | volume = 11661 | issue = 18 | pages = 95–1001233–1239 | date =January 1990August 1997 | pmid = 22959699301101 | doi = 10.10161271/S0022bbb.61.1233 | doi-3476(05)81652-Xaccess = free }}</ref>
 
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<ref name="ShenKishnan">{{cite journal | vauthors =Shen JKishnani PS, BaoAustin YSL, LiuArn HMP, LeeBali PDS, LeonardBoney JVA, ChenCase YTLE, |Chung titleWK, =Desai MutationsDM, inEl-Gharbawy exonA, 3Haller ofR, theSmit glycogenGP, debranchingSmith enzymeAD, geneHobson-Webb areLD, associatedWechsler withSB, glycogenWeinstein storageDA, diseaseWatson typeMS III| thattitle is= differentiallyGlycogen expressedstorage indisease livertype III diagnosis and musclemanagement guidelines | journal = J.Genetics Clin.in Invest.Medicine | volume = 9812 | issue = 27 | pages = 352–7446–463 | date = July 19962010 | pmid = 875564420631546 | pmcdoi = 50743710.1097/GIM.0b013e3181e655b6 | doi-access = 10.1172/JCI118799free }}</ref>
 
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}}
 
== External links ==
{{Commons category}}
*[http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=gsd3 GeneReviews/NCBI/NIH/UW entry on Glycogen Storage Disease Type III]
* [httphttps://www.ncbi.nlm.nih.gov/omimbooks/NBK26372/232400,610860,232400,610860 OMIMGeneReviews/NCBI/NIH/UW entriesentry on Glycogen Storage Disease Type III]
* [https://omim.org/search?index=entry&start=1&limit=10&search=232400+610860+232400+610860&sort=score+desc&field=number OMIM entries on Glycogen Storage Disease Type III]
* {{MeSH name|Glycogen+debranching+enzyme}}
 
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{{Enzymes}}
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[[Category:Carbohydrate metabolism]]
[[Category:EC 2.4.1]]
[[Category:EC 3.2.1]]