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Glycogenin

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glycogenin glucosyltransferase
Glycogenin structure (from rabbit).[1]
Identifiers
EC no.2.4.1.186
CAS no.117590-73-5
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BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
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NCBIproteins

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 reactions:

UDP-alpha-D-glucose + glycogenin ⇌ UDP + alpha-D-glucosylglycogenin
UDP-alpha-D-glucose + a glucosyl-glycogenin ⇌ (1,4-alpha-D-glucosyl)n-glucosyl glucogenin + UDP + H+

Thus, the two substrates of this enzyme are UDP-alpha-D-glucose and glycogenin, whereas its two products are UDP and alpha-D-glucosylglycogenin.[2][3]

Nomenclature

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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.

One may also notice that the naming of glycogenin hints at its function, with the glyco prefix referring to a carbohydrate and the genin suffix derived from the Latin genesis meaning novel, source, or beginning. This hints at the role of glycogenin to simply start glycogen synthesis before glycogen synthase takes over.

Discovery

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Glycogenin was discovered in 1984 by Dr. William J. Whelan, a fellow of the Royal Society of London and former professor of Biochemistry at the University of Miami.[4]

Function

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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, 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.

Glycogenin is able to use the other two pyrimidine nucleotides as well, namely CDP-glucose and TDP-glucose, in addition to its native substrate, UDP-glucose.[5]

Structure

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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.[6]

Isozymes

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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.[7]

glycogenin 1
Identifiers
SymbolGYG1
Alt. symbolsGYG
NCBI gene2992
HGNC4699
OMIM603942
RefSeqNM_004130
UniProtP46976
Other data
EC number2.4.1.186
LocusChr. 3 q24-q25.1
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StructuresSwiss-model
DomainsInterPro
glycogenin 2
Identifiers
SymbolGYG2
NCBI gene8908
HGNC4700
OMIM300198
RefSeqNM_003918
UniProtO15488
Other data
EC number2.4.1.186
LocusChr. X p22.3
Search for
StructuresSwiss-model
DomainsInterPro

References

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  1. ^ 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.
  2. ^ Barengo R, Krisman CR (May 1978). "Initiation of glycogen biosynthesis in Escherichia coli. Studies of the properties of the enzymes involved". Biochimica et Biophysica Acta (BBA) - General Subjects. 540 (2): 190–6. doi:10.1016/0304-4165(78)90131-9. PMID 418819.
  3. ^ Butler NA, Lee EY, Whelan WJ (May 1977). "A protein-bound glycogen component of rat liver". Carbohydrate Research. 55: 73–82. doi:10.1016/s0008-6215(00)84444-4. PMID 861979.
  4. ^ 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.
  5. ^ Alonso, Miriam D.; Lagzdins, Erik J.; Lomako, Joseph; Lomako, Wieslawa M.; Whelan, William J. (1995-02-13). "New and specific nucleoside diphosphate glucose substrates for glycogenin". FEBS Letters. 359 (2–3): 110–112. doi:10.1016/0014-5793(95)00018-5. ISSN 0014-5793.
  6. ^ Katch, Victor L.; McArdle, William D.; Katch, Frank I. (2007). Exercise physiology: energy, nutrition, and human performance. Philadelphia: Lippincott Williams and Wilkins. p. 12. ISBN 978-0-7817-4990-9.
  7. ^ 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.

Further reading

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