Glycogenin

Glycogenin is an enzyme involved in converting glucose to glycogen. It acts as a primer, by polymerizing the first few glucose molecules, after which other enzymes take over. It is a homodimer of 37-kDa subunits and is classified as a glycosyltransferase.

It catalyzes the chemical reaction:

UDP-alpha-D-glucose + glycogenin $\rightleftharpoons$ UDP + alpha-D-glucosylglycogenin

Thus, the two substrates of this enzyme are UDP-alpha-D-glucose and glycogenin, whereas its two products are UDP and alpha-D-glucosylglycogenin.

Nomenclature

This enzyme belongs to the family of glycosyltransferases, specifically the hexosyltransferases. The 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.^[2]

Function

The main enzyme involved in glycogen polymerisation, glycogen synthase, can only add to an existing chain of at least 8 glucose residues. Glycogenin acts as the primer, to which further glucose monomers may be added. It achieves this by 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

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 30.000 glucose units.^[1]

Isozymes

In humans, there are two 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.^[3]

glycogenin 1
Identifiers
Symbol	GYG1
Alt. symbols	GYG
Entrez	2992
HUGO	4699
OMIM	603942
RefSeq	NM_004130
UniProt	P46976
Other data
Locus	Chr. 3 q24-q25.1

glycogenin 2
Identifiers
Symbol	GYG2
Entrez	8908
HUGO	4700
OMIM	300198
RefSeq	NM_003918
UniProt	O15488
Other data
Locus	Chr. X p22.3

References

↑ PDB 1LL3; Gibbons BJ, Roach PJ, Hurley TD (May 2002). "Crystal structure of the autocatalytic initiator of glycogen biosynthesis, glycogenin". J. Mol. Biol. 319 (2): 463–77. doi:10.1016/S0022-2836(02)00305-4. PMID 12051921.
↑ Whelan WJ (September 1998). "Pride and prejudice: the discovery of the primer for glycogen synthesis". Protein Sci. 7 (9): 2038–41. doi:10.1002/pro.5560070921. PMC 2144155. PMID 9761486.
↑ Moslemi AR, Lindberg C, Nilsson J, Tajsharghi H, Andersson B, Oldfors A (April 2010). "Glycogenin-1 deficiency and inactivated priming of glycogen synthesis". N. Engl. J. Med. 362 (13): 1203–10. doi:10.1056/NEJMoa0900661. PMID 20357282.

External links

glycogenin at the US National Library of Medicine Medical Subject Headings (MeSH)
http://molbio.med.miami.edu/NewWebsite/Whelan.htm

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