View source for Glycogenin

{{Infobox enzyme 
| Name = glycogenin glucosyltransferase
| AltNames = 
| EC_number = 2.4.1.186
| CAS_number= 117590-73-5
| image =  Rabbit muscle glycogenin structure.jpg
| caption = Glycogenin structure (from rabbit).<ref name="pmid12051921">{{PDB|1LL3}}; {{cite journal | vauthors = Gibbons BJ, Roach PJ, Hurley TD | title = Crystal structure of the autocatalytic initiator of glycogen biosynthesis, glycogenin | journal = J. Mol. Biol. | volume = 319 | issue = 2 | pages = 463–77 |date=May 2002 | pmid = 12051921 | doi = 10.1016/S0022-2836(02)00305-4 | url =  }}</ref>
}}

'''Glycogenin''' is an enzyme involved in converting [[glucose]] to [[glycogen]]. It acts as a [[primer (molecular biology)|primer]], by polymerizing the first few glucose molecules, after which other enzymes take over.  It is a [[homodimer]] of 37-[[Atomic mass unit|kDa]] subunits and is classified as a [[glycosyltransferase]].

It [[catalysis|catalyzes]] the [[chemical reaction]]:

:UDP-alpha-D-glucose + glycogenin {{eqm}} UDP + alpha-D-glucosylglycogenin

Thus, the two [[substrate (biochemistry)|substrates]] of this enzyme are [[UDP-glucose|UDP-alpha-D-glucose]] and '''glycogenin''', whereas its two [[product (chemistry)|products]] are [[uridine diphosphate|UDP]] and [[alpha-D-glucosylglycogenin]].

== Nomenclature ==

This enzyme belongs to the family of [[glycosyltransferase]]s, specifically the hexosyltransferases.  The [[List of enzymes|systematic name]] of this enzyme class is '''UDP-alpha-D-glucose:glycogenin alpha-D-glucosyltransferase'''. Other names in common use include:
*  glycogenin,
* priming glucosyltransferase, and 
* UDP-glucose:glycogenin glucosyltransferase.

== Discovery ==

Glycogenin was discovered in 1984 by Dr. William J. Whelan, a fellow of the [[Royal Society of London]] and current professor of Biochemistry at the [[University of Miami]].<ref name="pmid9761486">{{cite journal | author = Whelan WJ | title = Pride and prejudice: the discovery of the primer for glycogen synthesis | journal = Protein Sci. | volume = 7 | issue = 9 | pages = 2038–41 |date=September 1998 | pmid = 9761486 | pmc = 2144155 | doi = 10.1002/pro.5560070921 | url = }}</ref>

== Function ==

The main enzyme involved in glycogen [[polymerisation]], [[glycogen synthase]] in the liver and in the muscle glycogen synthesis is initiated by UDP-Glucose, can only add to an existing chain of at least 3 [[glucose]] residues. Glycogenin acts as the [[Primer (molecular biology)|primer]], to which further glucose [[monomer]]s may be added. It achieves this by [[catalysis|catalyzing]] the addition of glucose to itself (autocatalysis) by first binding glucose from [[UDP-glucose]] to the [[hydroxyl]] group of Tyr-194. Seven more glucoses can be added, each derived from UDP-glucose, by glycogenin's glucosyltransferase activity. Once sufficient residues have been added, glycogen synthase takes over extending the chain. Glycogenin remains covalently attached to the reducing end of the glycogen [[molecule]].

Evidence accumulates that a '''priming protein''' may be a fundamental property of polysaccharide synthesis in general; the molecular details of mammalian glycogen biogenesis may serve as a useful model for other systems.

== Structure ==
[[File:Glycogen structure.svg|thumb|300px|left|2-D cross-sectional view of [[glycogen]]. A core protein of ''glycogenin'' is surrounded by branches of [[glucose]] units. The entire globular complex may contain approximately 30&nbsp;000 glucose units.<ref name="isbn0-7817-4990-5">{{cite book | author = Katch, Victor L. | author2 = McArdle, William D. | author3 = Katch, Frank I. | others = | title = Exercise physiology: energy, nutrition, and human performance | edition = | language = | publisher = Lippincott Williams and Wilkins | location = Philadelphia | year = 2007 | origyear = | pages = 12 | quote = | isbn = 978-0-7817-4990-9 | oclc = | doi = | url = | accessdate = }}</ref>]]
{{Clear}}

== Isozymes ==

In humans, there are two [[Protein isoform|isoforms]] of glycogenin — glycogenin-1, encoded by GYG1, and expressed in muscle; and glycogenin-2, encoded by GYG2,and expressed in the liver and cardiac muscle, but not skeletal muscle. Patients have been found with defective GYG1, resulting in muscle cells with the inability to store glycogen, and consequential weakness and heart disease.<ref name="pmid20357282">{{cite journal | vauthors = Moslemi AR, Lindberg C, Nilsson J, Tajsharghi H, Andersson B, Oldfors A | title = Glycogenin-1 deficiency and inactivated priming of glycogen synthesis | journal = N. Engl. J. Med. | volume = 362 | issue = 13 | pages = 1203–10 |date=April 2010 | pmid = 20357282 | doi = 10.1056/NEJMoa0900661 | url =  }}</ref>

{|
|- valign="top"
|{{infobox protein
|Name=glycogenin 1
|caption=
|image=
|width=
|HGNCid=4699
|Symbol=GYG1
|AltSymbols=GYG
|EntrezGene=2992
|OMIM=603942
|RefSeq=NM_004130
|UniProt=P46976
|PDB=
|ECnumber=2.4.1.186
|Chromosome=3
|Arm=q
|Band=24
|LocusSupplementaryData=-q25.1
}}
|{{infobox protein
|Name=glycogenin 2
|caption=
|image=
|width=
|HGNCid=4700
|Symbol=GYG2
|AltSymbols=
|EntrezGene=8908
|OMIM=300198
|RefSeq=NM_003918
|UniProt=O15488
|PDB=
|ECnumber=2.4.1.186
|Chromosome=X
|Arm=p
|Band=22.3
|LocusSupplementaryData=
}}
|}

==References==
{{reflist|33em}}

== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Krisman CR, Barengo R | year = 1975 | title = A precursor of glycogen biosynthesis: alpha-1,4-glucan-protein | journal = Eur. J. Biochem.  | volume = 52 | pages = 117&ndash;23  | pmid = 809265 | doi = 10.1111/j.1432-1033.1975.tb03979.x | issue = 1 }}
* {{cite journal | vauthors = Pitcher J, Smythe C, Campbell DG, Cohen P | year = 1987 | title = Identification of the 38-kDa subunit of rabbit skeletal muscle glycogen synthase as glycogenin | journal = Eur. J. Biochem.  | volume = 169 | pages = 497&ndash;502  | pmid = 3121316 | doi = 10.1111/j.1432-1033.1987.tb13637.x | issue = 3 }}
* {{cite journal | vauthors = Pitcher J, Smythe C, Cohen P | year = 1988 | title = Glycogenin is the priming glucosyltransferase required for the initiation of glycogen biogenesis in rabbit skeletal muscle | journal = Eur. J. Biochem.  | volume = 176 | pages = 391&ndash;5  | pmid = 2970965 | doi = 10.1111/j.1432-1033.1988.tb14294.x | issue = 2 }}
* Berman, M.C. and Opie, L.A. (Eds.), Membranes and Muscle, ICSU Press/IRL Press, Oxford, 1985, p.&nbsp;65-84.
* {{cite journal | vauthors = Rodriguez IR, Whelan WJ | year = 1985 | title = A novel glycosyl-amino acid linkage: rabbit-muscle glycogen is covalently linked to a protein via tyrosine | journal = Biochem. Biophys. Res. Commun.  | volume = 132 | pages = 829&ndash;36  | pmid = 4062948 | doi = 10.1016/0006-291X(85)91206-9 | issue = 2 }}
* {{cite journal | vauthors = Lomako J, Lomako WM, Whelan WJ | year = 1988 | title = A self-glucosylating protein is the primer for rabbit muscle glycogen biosynthesis | journal = FASEB J.  | volume = 2 | pages = 3097&ndash;103  | pmid = 2973423 | issue = 15 }}
* {{cite journal | vauthors = Alonso MD, Lomako J, Lomako WM, Whelan WJ | year = 1995 | title = Catalytic activities of glycogenin additional to autocatalytic self-glucosylation | journal = J. Biol. Chem.  | volume = 270 | pages = 15315&ndash;9  | pmid = 7797519 | doi = 10.1074/jbc.270.25.15315 | issue = 25 }}
* {{cite journal | vauthors = Alonso MD, Lomako J, Lomako WM, Whelan WJ | year = 1995 | title = A new look at the biogenesis of glycogen | journal = FASEB J.  | volume = 9 | pages = 1126&ndash;37  | pmid = 7672505 | issue = 12 }}
* {{cite journal | vauthors = Mu J, Roach PJ | year = 1998 | title = Characterization of human glycogenin-2, a self-glucosylating initiator of liver glycogen metabolism | journal = J. Biol. Chem.  | volume = 273 | pages = 34850&ndash;6  | pmid = 9857012 | doi = 10.1074/jbc.273.52.34850 | issue = 52 }}
{{refend}}

==External links==
{{Commonscat}}
*{{MeshName|glycogenin}}
*[http://molbio.med.miami.edu/NewWebsite/Whelan.htm molbio.med.miami.edu]

{{Glycosyltransferases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

[[Category:EC 2.4.1]]
[[Category:Enzymes of known structure]]