Glycogenin

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glycogenin glucosyltransferase
Rabbit muscle glycogenin structure.jpg
Glycogenin structure (from rabbit). [1]
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EC no. 2.4.1.186
CAS no. 117590-73-5
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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.

Contents

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

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:

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

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

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.

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. Glycogen structure.svg
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.

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. [6]

glycogenin 1
Identifiers
SymbolGYG1
Alt. symbolsGYG
NCBI gene 2992
HGNC 4699
OMIM 603942
RefSeq NM_004130
UniProt P46976
Other data
EC number 2.4.1.186
Locus Chr. 3 q24-q25.1
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Structures Swiss-model
Domains InterPro
glycogenin 2
Identifiers
SymbolGYG2
NCBI gene 8908
HGNC 4700
OMIM 300198
RefSeq NM_003918
UniProt O15488
Other data
EC number 2.4.1.186
Locus Chr. X p22.3
Search for
Structures Swiss-model
Domains InterPro

Related Research Articles

<span class="mw-page-title-main">Glycogen</span> Glucose polymer used as energy store in animals

Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. It is the main storage form of glucose in the human body.

Glycogenesis is the process of glycogen synthesis, in which glucose molecules are added to chains of glycogen for storage. This process is activated during rest periods following the Cori cycle, in the liver, and also activated by insulin in response to high glucose levels.

<span class="mw-page-title-main">Glycogen synthase</span> Enzyme class, includes all types of glycogen/starch synthases

Glycogen synthase is a key enzyme in glycogenesis, the conversion of glucose into glycogen. It is a glycosyltransferase that catalyses the reaction of UDP-glucose and n to yield UDP and n+1.

<span class="mw-page-title-main">Glycogen debranching enzyme</span> Mammalian protein found in Homo sapiens

The glycogen debranching enzyme, in humans, is the protein encoded by the gene AGL. This enzyme is essential for the breakdown of glycogen, which serves as a store of glucose in the body. It has separate glucosyltransferase and glucosidase activities.

<span class="mw-page-title-main">Glycogen branching enzyme</span> Mammalian protein involved in glycogen production

1,4-alpha-glucan-branching enzyme, also known as brancher enzyme or glycogen-branching enzyme is an enzyme that in humans is encoded by the GBE1 gene.

In enzymology, a 1,4-alpha-glucan 6-alpha-glucosyltransferase is an enzyme that catalyzes the chemical reaction that transfers an alpha-D-glucosyl residue in a 1,4-alpha-D-glucan to the primary hydroxyl group of glucose or 1,4-alpha-D-glucan.

<span class="mw-page-title-main">UTP—glucose-1-phosphate uridylyltransferase</span> Class of enzymes

UTP—glucose-1-phosphate uridylyltransferase also known as glucose-1-phosphate uridylyltransferase is an enzyme involved in carbohydrate metabolism. It synthesizes UDP-glucose from glucose-1-phosphate and UTP; i.e.,

1,3-Beta-glucan synthase is a glucosyltransferase enzyme involved in the generation of beta-glucan in fungi. It serves as a pharmacological target for antifungal drugs such as caspofungin, anidulafungin, and micafungin, deemed 1,3-Beta-glucan synthase inhibitors. Under the CAZy classification system, fungi and plant members fall in the glycosyltransferase 48 family (GT48). Some members of the glycosyltransferase 2 family, such as the curdlan synthase CrdS, also has a similar activity.

In enzymology, an alpha-1,4-glucan-protein synthase (ADP-forming) is an enzyme that catalyzes the chemical reaction

In enzymology, an alpha,alpha-trehalose-phosphate synthase (UDP-forming) is an enzyme that catalyzes the chemical reaction

In enzymology, a cellulose synthase (GDP-forming) is an enzyme that catalyzes the chemical reaction

In enzymology, a dolichyl-phosphate beta-glucosyltransferase is an enzyme that catalyzes the chemical reaction

In enzymology, a 4-alpha-glucanotransferase is an enzyme that catalyzes a chemical reaction that transfers a segment of a 1,4-alpha-D-glucan to a new position in an acceptor carbohydrate, which may be glucose or a 1,4-alpha-D-glucan.

In enzymology, an indole-3-acetate beta-glucosyltransferase is an enzyme that catalyzes the chemical reaction

In enzymology, a NDP-glucose—starch glucosyltransferase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Starch synthase</span> Enzyme family

In enzymology, a starch synthase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Sucrose-phosphate synthase</span> Class of enzymes

Sucrose-phosphate synthase (SPS) is a plant enzyme involved in sucrose biosynthesis. Specifically, this enzyme catalyzes the transfer of a hexosyl group from uridine diphosphate glucose (UDP-glucose) to D-fructose 6-phosphate to form UDP and D-sucrose-6-phosphate. This reversible step acts as the key regulatory control point in sucrose biosynthesis, and is an excellent example of various key enzyme regulation strategies such as allosteric control and reversible phosphorylation.

<span class="mw-page-title-main">Sucrose synthase</span> Protein family

In enzymology, a sucrose synthase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Glycogenin-1</span> Protein-coding gene in the species Homo sapiens

Glycogenin-1 is an enzyme that is involved in the biosynthesis of glycogen. It is capable of self-glucosylation, forming an oligosaccharide primer that serves as a substrate for glycogen synthase. This is done through an inter-subunit mechanism. It also plays a role in glycogen metabolism regulation. Recombinant human glycogenin-1 was expressed in E. coli and purified using conventional chromatography techniques.

Glucosyl-3-phosphoglycerate synthase is an enzyme with systematic name NDP-glucose:3-phospho-D-glycerate 2-alpha-D-glucosyltransferase. This enzyme catalyses the following chemical reaction

References

  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. ↑ 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.
  6. ↑ 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.

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