Glycogen debranching enzyme: Difference between revisions

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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]]

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{{PBB|geneid=178 }}

{{Infobox_gene}}

{{enzyme

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"/>

| 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 thoughthrough 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 though an α -1,6 glycosidic linkage<ref name="Berg"/>

{|class=wikitable

* 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/>

|{{infobox enzyme

| Name = [[4-alpha-glucanotransferase|4-α-glucanotransferase]]

[[File:Glycosidase mechanism.png]]

| image = =

| width =

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.

| 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=GillardGillard_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 />

== PathologyClinical significance ==

{{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 | authorvauthors = 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 | yeardate = June 2010 | month = June | pmid = 20187119 | doi = 10.1002/prot.22697 | url = | issns2cid = 28334066 }}</ref>

<ref name="Bao">{{cite journal | authorvauthors = 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 = 155–65155–165 | yeardate = December 1996 | month = December | pmid = 8954797 | doi = 10.1006/geno.1996.0611| url = | issn = }}</ref>

<ref name="Berg">{{cite book | authorvauthors = Stryer L, Lubert; Berg, Jeremy Mark;JM, Tymoczko, John L. | authorlink = | editor = | others =JL | title = Biochemistry | edition = 6th | language = | publisher = W.H. Freeman | ___location = San Francisco | year = 2007 | origyear = | pages = | quote = | isbn = 978-0-7167-8724-5 | oclc = | doi = | url = | accessdate =2 }}</ref>

<ref name="Dauvillée">{{cite journal | authorvauthors = Dauvillée D, Kinderf IS, Li Z, Kosar-Hashemi B, Samuel MS, Rampling L, Ball S, Morell MK | title = Role of the Escherichia coli glgX gene in glycogen metabolism | journal = J.Journal Bacteriol.of Bacteriology | volume = 187 | issue = 4 | pages = 1465–731465–1473 | yeardate = February 2005 | month = February | pmid = 15687211 | pmc = 545640 | doi = 10.1128/JB.187.4.1465-1473.2005 | url = | issn = }}</ref>

<ref name="Nakayama">{{cite journal | authorvauthors = Nakayama A, Yamamoto K, Tabata S | title = Identification of the catalytic residues of bifunctional glycogen debranching enzyme | journal = J.The Biol.Journal Chem.of Biological Chemistry | volume = 276 | issue = 31 | pages = 28824–828824–28828 | yeardate = August 2001 | month = August | pmid = 11375985 | doi = 10.1074/jbc.M102192200 | urldoi-access = | issn =free }}</ref>

<ref name="Chen">{{cite journal | authorvauthors = Chen YT, He JK, Ding JH, Brown BI | title = Glycogen debranching enzyme: purification, antibody characterization, and immunoblot analyses of type III glycogen storage disease | journal = Am.American J.Journal Hum.of Human Genet.Genetics | volume = 41 | issue = 6 | pages = 1002–151002–1015 | yeardate = December 1987 | month = December | pmid = 2961257 | pmc = 1684360 | doi = | url = | issn = }}</ref>

<ref name="UniProt P35573">{{cite web | url = httphttps://www.uniprot.org/uniprot/P35573 | title = Glycogen debranching enzyme - Homo sapiens (Human) | author = | authorlink = | coauthors = | date = | format = | work = | publisher = UniProt | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = }}</ref>

<ref name="GillardGillard_80">{{cite journal | authorvauthors = Gillard BK, White RC, Zingaro RA, Nelson TE | title = 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 | journal = J.The Biol.Journal Chem.of Biological Chemistry | volume = 255 | issue = 18 | pages = 8451–78451–8457 | yeardate = September 1980 | month = September | pmid = 6447697 | doi = | url =10.1016/S0021-9258(18)43517-X | issndoi-access = free }}</ref>

<ref name="WooGillard">{{cite journal | authorvauthors = WooGillard EJBK, LeeNelson S,TE Cha| H,title Park= JTAmylo-1,6-glucosidase/4-alpha-glucanotransferase: Yoonuse SM,of Songreversible HN,substrate Parkmodel KHinhibitors |to titlestudy =the Structuralbinding insightand intoactive thesites bifunctionalof mechanismrabbit ofmuscle the glycogen-debranching enzyme TreX from the archaeon Sulfolobus solfataricus | journal = J. Biol. Chem.Biochemistry | volume = 28316 | issue = 4218 | pages = 28641–83978–3987 | yeardate = 2008September | month = October1977 | pmid = 18703518 | pmc = 2661413269742 | doi = 10.10741021/jbc.M802560200 | url = | issn =bi00637a007 }}</ref>

<ref name="UniProt A8QX06Woo">{{cite webjournal | urlvauthors = http://www.uniprot.org/uniprot/A8QX06Woo EJ, Lee S, Cha H, Park JT, Yoon SM, Song HN, Park KH | title = TreXStructural -insight Actinoplanesinto sp.the SN223/29bifunctional |mechanism authorof =the |glycogen-debranching authorlinkenzyme =TreX |from coauthorsthe =archaeon Sulfolobus solfataricus | datejournal = |The formatJournal =of Biological Chemistry | workvolume = 283 | publisherissue = UniProt42 | pages = 28641–28648 | languagedate = October 2008 | archiveurlpmid = 18703518 | archivedatepmc = 2661413 | quotedoi = 10.1074/jbc.M802560200 | accessdatedoi-access = free }}</ref>

<ref name="UniProt A7ZSW4A8QX06">{{cite web | url = httphttps://www.uniprot.org/uniprot/A7ZSW4A8QX06 | title = Glycogen debranching enzymeTreX - EscherichiaActinoplanes coli O139:H28 (strain E24377Asp. SN223/ ETEC) | author = | authorlink = | coauthors = | date = | format = | work =29 | publisher = UniProt | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = }}</ref>

<ref name="UniProt P15977A7ZSW4">{{cite web | url = httphttps://www.uniprot.org/uniprot/P15977A7ZSW4 | title = 4-alpha-glucanotransferaseGlycogen debranching enzyme - Escherichia coli O139:H28 (strain K12)E24377A |/ author = | authorlink = | coauthors = | date = | format = | work =ETEC) | publisher = | pages = | language = | archiveurl = | archivedate = | quote = | accessdate =UniProt }}</ref>

<ref name="UniProt P15977">{{cite web | url = https://www.uniprot.org/uniprot/P15977 | title = 4-alpha-glucanotransferase - Escherichia coli (strain K12) }}</ref>

<ref name="Park">{{cite journal | author = Park JT, Park HS, Kang HK, Hong JS, Cha H, Woo EJ, Kim JW, Kim MJ, Boos W, Lee S, Park KH | title = Oligomeric and functional properties of a debranching enzyme (TreX) from the archaeon Sulfobus solfataricus P2. | journal = Biocatalysis and Biotransformation | year = 2008 | volume = 26 | pages = 76–85 | doi = 10.1080/10242420701806652 }}</ref>

<ref name="TalentePark">{{cite journal | author vauthors=Park Talente GMJT, ColemanPark RAHS, AlterKang CHK, BakerHong LJS, BrownCha BIH, CannonWoo RAEJ, ChenKim YTJW, CriglerKim JFMJ, FerreiraBoos PW, HaworthLee JCS, HermanPark GE,KH Issenman| RM,title Keating= JP,Oligomeric Lindeand R,functional Roeproperties TF,of Seniora B,debranching Wolfsdorfenzyme JI(TreX) |from titlethe =archaeon GlycogenSulfobus storagesolfataricus disease in adultsP2. | journal = Ann.Biocatalysis Intern.and Med.Biotransformation | volumeyear = 1202008 | issuevolume = 326 | pagesissue = 218–261–2 | yearpages = 199476–85 | monthdoi = February10.1080/10242420701806652 | pmids2cid = 8273986 | doi = | url = | issn =83831481 }}</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 = Annals of Internal Medicine | volume = 120 | issue = 3 | pages = 218–226 | date = February 1994 | pmid = 8273986 | doi = 10.7326/0003-4819-120-3-199402010-00008 | s2cid = 24896145 }}</ref>

<ref name="Monga">{{cite book | author = Satdarshan P. S. Monga | title = Molecular Pathology of Liver Diseases (Molecular Pathology Library) | publisher = Springer | ___location = Berlin | year = 2010 | pages = | isbn = 1-4419-7106-8 }}</ref>

<ref name="HondohMonga">{{cite journalbook | authorvauthors = HondohMonga H, Saburi W, Mori H, ''et al.''SP | title = SubstrateMolecular recognition mechanismPathology of alpha-1,6-glucosidicLiver linkageDiseases hydrolyzing(Molecular enzyme,Pathology dextran glucosidase from Streptococcus mutansLibrary) | journalpublisher = J. Mol. Biol.Springer | volume___location = 378 | issue = 4 | pages = 913–22Berlin | year = 20082010 | monthisbn = May | pmid = 18395742 | doi = 10.1016/j.jmb.2008.03.016978-1-4419-7106-7 }}</ref>

<ref name="MCCarterHondoh">{{cite journal | authorvauthors = McCarterHondoh JDH, WithersSaburi SGW, Mori H, Okuyama M, Nakada T, Matsuura Y, Kimura A | title = MechanismsSubstrate recognition mechanism of enzymaticalpha-1,6-glucosidic glycosidelinkage hydrolysishydrolyzing enzyme, dextran glucosidase from Streptococcus mutans | journal = Curr.Journal Opin.of Struct.Molecular Biol.Biology | volume = 4378 | issue = 64 | pages = 885–92913–922 | yeardate = 1994May | month = December2008 | pmid = 771229218395742 | doi = 10.1016/0959-440X(94)90271-2| url =j.jmb.2008.03.016 }}</ref>

<ref name="GillardMCCarter">{{cite journal | authorvauthors = GillardMcCarter BKJD, NelsonWithers TESG | title = Amylo-1,6-glucosidase/4-alpha-glucanotransferase: useMechanisms of reversibleenzymatic substrateglycoside modelhydrolysis inhibitors| tojournal study= theCurrent bindingOpinion andin activeStructural sites of rabbit muscle debranching enzyme | journal = BiochemistryBiology | volume = 164 | issue = 186 | pages = 3978–87885–892 | yeardate = 1977December | month = September1994 | pmid = 2697427712292 | doi = 10.10211016/bi00637a0070959-440X(94)90271-2 }}</ref>

<ref name="Yamamoto">{{cite journal | authorvauthors = Yamamoto E, Makino Y, Omichi K | title = Active site mapping of amylo-alpha-1,6-glucosidase in porcine liver glycogen debranching enzyme using fluorogenic 6-O-alpha-glucosyl-maltooligosaccharides | journal = J.Journal Biochem.of Biochemistry | volume = 141 | issue = 5 | pages = 627–34627–634 | yeardate = May 2007 | month = May | pmid = 17317688 | doi = 10.1093/jb/mvm065 | doi-access = free }}</ref>

<ref name="Hers">{{cite journal | authorvauthors = Hers HG, Verhue W, Van hoof F | title = The determination of amylo-1,6-glucosidase | journal = Eur.European J.Journal Biochem.of Biochemistry | volume = 2 | issue = 3 | pages = 257–64257–264 | yeardate = October 1967 | month = October | pmid = 6078537 | doi = 10.1111/j.1432-1033.1967.tb00133.x }}</ref>

<ref name="Ding">{{cite journal | authorvauthors = Ding JH, de Barsy T, Brown BI, Coleman RA, Chen YT | title = Immunoblot analyses of glycogen debranching enzyme in different subtypes of glycogen storage disease type III | journal = J.The Pediatr.Journal of Pediatrics | volume = 116 | issue = 1 | pages = 95–100 | yeardate = January 1990 | month = January | pmid = 2295969 | doi = 10.1016/S0022-3476(05)81652-X }}</ref>

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<ref name="Kishnan">{{cite journal | author = Kishnani PS, Austin SL, Arn P, ''et al.'' | title = Glycogen storage disease type III diagnosis and management guidelines | journal = Genet. Med. | volume = 12 | issue = 7 | pages = 446–63 | year = 2010 | month = July | pmid = 20631546 | doi = 10.1097/GIM.0b013e3181e655b6 }}</ref>

}}

== 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}}

{{Glycogenesis and glycogenolysis enzymes}}

{{Glycosyltransferases}}

{{Sugar hydrolases}}

{{Glycosyltransferases}}

{{Enzymes}}

{{Portal bar|Biology|border=no}}

{{DEFAULTSORT:Glycogen Debranching Enzyme}}

[[Category:Carbohydrate metabolism]]

[[Category:EC 2.4.1]]

[[Category:EC 3.2.1]]