Glycogen branching enzyme

Last updated

GBE1
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases GBE1 , APBD, GBE, GSD4, glucan (1,4-alpha-), branching enzyme 1, 1,4-alpha-glucan branching enzyme 1
External IDs OMIM: 607839; MGI: 1921435; HomoloGene: 129; GeneCards: GBE1; OMA:GBE1 - orthologs
EC number 2.4.1.18
Orthologs
SpeciesHumanMouse
Entrez

2632

74185

Ensembl

ENSG00000114480

ENSMUSG00000022707

UniProt

Q04446

Q9D6Y9

RefSeq (mRNA)

NM_000158

NM_028803

RefSeq (protein)

NP_000149

NP_083079

Location (UCSC) Chr 3: 81.49 – 81.76 Mb Chr 16: 70.11 – 70.37 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
Glycogen branching enzyme
Identifiers
EC no. 2.4.1.18
CAS no. 9001-97-2
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO
Search
PMC articles
PubMed articles
NCBI proteins

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. [5]

Contents

Glycogen branching enzyme is an enzyme that adds branches to the growing glycogen molecule during the synthesis of glycogen, a storage form of glucose. More specifically, during glycogen synthesis, a glucose 1-phosphate molecule reacts with uridine triphosphate (UTP) to become UDP-glucose, an activated form of glucose. The activated glucosyl unit of UDP-glucose is then transferred to the hydroxyl group at the C-4 of a terminal residue of glycogen to form an α-1,4-glycosidic linkage, a reaction catalyzed by glycogen synthase. Importantly, glycogen synthase can only catalyze the synthesis of α-1,4-glycosidic linkages. Since glycogen is a readily mobilized storage form of glucose, the extended glycogen polymer is branched by glycogen branching enzyme to provide glycogen breakdown enzymes, such as glycogen phosphorylase, with many terminal residues for rapid degradation. Branching also importantly increases the solubility and decreases the osmotic strength of glycogen. [6]

The protein encoded by this gene is a glycogen branching enzyme that catalyzes the transfer of alpha-1,4-linked glucosyl units from the outer end of a glycogen chain to an alpha-1,6 position on the same or a neighboring glycogen chain. Branching of the chains is essential to increase the solubility of the glycogen molecule and, consequently, in reducing the osmotic pressure within cells. The highest levels of this enzyme are found in liver and muscle cells. Mutations in this gene are associated with glycogen storage disease type IV (also known as Andersen's disease).

Nomenclature

This enzyme belongs to the family of transferases, to be specific, those glycosyltransferases that transfer hexoses (hexosyltransferases). The systematic name of this enzyme class is 1,4-alpha-D-glucan:1,4-alpha-D-glucan 6-alpha-D-(1,4-alpha-D-glucano)-transferase. Other names in common use include branching enzyme, amylo-(1,4→1,6)-transglycosylase, Q-enzyme, alpha-glucan-branching glycosyltransferase, amylose isomerase, enzymatic branching factor, branching glycosyltransferase, enzyme Q, glucosan transglycosylase, 1,4-alpha-glucan branching enzyme 1, plant branching enzyme, alpha-1,4-glucan:alpha-1,4-glucan-6-glycosyltransferase, and starch branching enzyme. This enzyme participates in starch and sucrose metabolism.

Gene

GBE is encoded by the GBE1 gene. [5] [7] [8] [9]

Through Southern blot analysis of DNA derived from human/rodent somatic cell hybrids, GBE1 has been identified as an autosomal gene located on the short arm of chromosome 3 at position 12.3. [7] [8] [9] [10] The human GBE gene was also isolated by a function complementation of the Saccharomyces cerevisiae GBE deficiency. [10] From the isolated cDNA, the length of the gene was found to be approximately 3 kb. [10] Additionally, the coding sequence was found to comprise 2,106 base pairs and encode a 702-amino acid long GBE. The molecular mass of human GBE was calculated to be 80,438 Da. [10]

Structure

Structure of glycogen branching enzyme found in E. Coli E. Coli Glycogen Branching Enzyme.png
Structure of glycogen branching enzyme found in E. Coli

Glycogen branching enzyme belongs to the α-amylase family of enzymes, which include α-amylases, pullulanas/isoamylase, cyclodextrin glucanotransferase (CGT), and branching enzyme. [11] [12] Shown by x-ray crystallography, glycogen branching enzyme has four marginally asymmetric units each that are organized into three domains: an amino-terminal domain, involved in determining the length of the chain transfer, a carboxyl-terminal domain, involved in substrate preference and catalytic capacity, and a central (α/β) barrel catalytic domain. [11] [13] [14] [15] The amino-terminal domain consists of 128 residues arranged in seven β-strands, the carboxyl-terminal domain with 116 residues also organized in seven β-strands, and the (α/β) barrel domain with 372 residues. While the central (α/β) barrel domain is common in members of the α-amylase family, numerous variations exist between the various barrel domains. Additionally, there are striking differences between the loops connecting elements of the secondary structure among these various α-amylase members, especially around the active site. In comparison to the other family members, glycogen binding enzyme has shorter loops, which result in a more open cavity, favorable to the binding of a bulkier substrate such as branched sugar. Through primary structure analysis and the x-ray crystallographic structures of the members of the α-amylase family, seven residue were conserved, Asp335, His340, Arg403, Asp 405, Glu458, His525, and Asp526 (E coli. numbering). These residues are implicated in catalysis and substrate binding. [11]

Glycogen binding enzymes in other organisms have also been crystallized and structurally determined, demonstrating both similarity and variation to GBE found in Escherichia coli. [16] [17] [18] [19]

Function

Scheme demonstrating the function of glycogen branching enzyme Glycogen Branching Enzyme Scheme.tif
Scheme demonstrating the function of glycogen branching enzyme

In glycogen, every 10 to 14 glucose units, a side branch with an additional chain of glucose units occurs. The side chain attaches at carbon atom 6 of a glucose unit, an α-1,6-glycosidic bond. This connection is catalyzed by a branching enzyme, generally given the name α-glucan branching enzyme. A branching enzyme attaches a string of seven glucose units (with some minor variation to this number) to the carbon at the C-6 position on the glucose unit, forming the α-1,6-glycosidic bond. The specific nature of this enzyme means that this chain of 7 carbons is usually attached to a glucose molecule that is in position three from the non-reducing end of another chain. Because the enzyme works with such specificity regarding the number of glucose units transferred and the position to which they are transferred, the enzyme creates the very characteristic, highly branched glycogen molecule. [20]

Clinical significance

Mutations in this gene are associated with glycogen storage disease type IV (also known as Andersen's disease) in newborns and with adult polyglucosan body disease. [5] [21]

Approximately 40 mutations in the GBE1 gene, most resulting in a point mutation in the glycogen branching enzyme, have led to the early childhood disorder, glycogen storage disease type IV (GSD IV). [9] This disease is characterized by a severe depletion or complete absence of GBE, resulting in the accumulation of abnormally structured glycogen, known as polyglucosan bodies. [9] Glycogen buildup leads to increased osmotic pressure resulting in cellular swelling and death. [9] The tissues most affected by this disease are the liver, heart, and neuromuscular system, areas with the greatest levels of glycogen accumulation. [9] [22] Abnormal glycogen buildup in the liver interferes with liver functioning and can result in an enlarged liver and liver disease. [9] [23] In muscles, the inability of cells to efficiently breakdown glycogen due to the severe reduction or absence of branching can lead to muscle weakness and atrophy. [9] At least three mutations in the GBE1 gene have been found to cause another disease called adult polyglucosan body disease (APBD). [9] [24] While in GSD IV GBE activity is undetectable or minimally detectable, APBD is characterized by reduced or even normal GBE activity. [24] In this disease, abnormal glycogen can build up in neurons leading to a spectrum of problems. Specifically, some disease characteristics are gait difficulties from mixed upper and lower motor neuron involvement sensory loss in lower extremities, and neurogenic bladder, a problem in which a person lacks bladder control due to a brain, spinal cord, or nerve condition. [24] [25]

Related Research Articles

<span class="mw-page-title-main">Glycogenolysis</span> Breakdown of glycogen

Glycogenolysis is the breakdown of glycogen (n) to glucose-1-phosphate and glycogen (n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase.

<span class="mw-page-title-main">Maltase</span> Enzyme

Maltase is an informal name for a family of enzymes that catalyze the hydrolysis of disaccharide maltose into two simple sugars of glucose. Maltases are found in plants, bacteria, yeast, humans, and other vertebrates.

<span class="mw-page-title-main">Glycogen phosphorylase</span> Class of enzymes

Glycogen phosphorylase is one of the phosphorylase enzymes. Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond. Glycogen phosphorylase is also studied as a model protein regulated by both reversible phosphorylation and allosteric effects.

Glycogen-branching enzyme deficiency (GBED) is an inheritable glycogen storage disease affecting American Quarter Horses and American Paint Horses. It leads to abortion, stillbirths, or early death of affected animals. The human form of the disease is known as glycogen storage disease type IV.

<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 storage disease type IV</span> Human disease

Glycogen storage disease type IV (GSD IV), or Andersen's Disease, is a form of glycogen storage disease, which is caused by an inborn error of metabolism. It is the result of a mutation in the GBE1 gene, which causes a defect in the glycogen branching enzyme. Therefore, glycogen is not made properly and abnormal glycogen molecules accumulate in cells; most severely in cardiac and muscle cells. The severity of this disease varies on the amount of enzyme produced. GSD IV is autosomal recessive, which means each parent has a mutant copy of the gene, but show no symptoms of the disease. Having an autosomal recessive inheritance pattern, males and females are equally likely to be affected by Andersen's disease. Classic Andersen's disease typically becomes apparent during the first few months after the patient is born. Approximately 1 in 20,000 to 25,000 newborns have a glycogen storage disease. Andersen's disease affects 1 in 800,000 individuals worldwide, with 3% of all GSDs being type IV. The disease was described and studied first by Dorothy Hansine Andersen.

<span class="mw-page-title-main">Glucose 6-phosphatase</span> Enzyme

Boron, Walter F.; Boulpaep, Emile L., eds. (2017). Medical Physiology (3rd ed.). Philadelphia, PA: Elsevier. ISBN 978-1-4557-4377-3.

β-Amylase Enzyme that hydrolyses alpha-1,4-D-glucosidic bonds in polysaccharides

β-Amylase is an enzyme with the systematic name 4-α-D-glucan maltohydrolase. It catalyses the following reaction:

α-Glucosidase Enzyme

α-Glucosidase (EC 3.2.1.20, is a glucosidase located in the brush border of the small intestine that acts upon α bonds:

<span class="mw-page-title-main">Phosphorylase kinase</span>

Phosphorylase kinase (PhK) is a serine/threonine-specific protein kinase which activates glycogen phosphorylase to release glucose-1-phosphate from glycogen. PhK phosphorylates glycogen phosphorylase at two serine residues, triggering a conformational shift which favors the more active glycogen phosphorylase "a" form over the less active glycogen phosphorylase b.

Equine polysaccharide storage myopathy is a hereditary glycogen storage disease of horses that causes exertional rhabdomyolysis. It is currently known to affect the following breeds American Quarter Horses, American Paint Horses, Warmbloods, Cobs, Dales Ponies, Thoroughbreds, Arabians, New Forest ponies, and a large number of Heavy horse breeds. While incurable, PSSM can be managed with appropriate diet and exercise. There are currently 2 subtypes, known as Type 1 PSSM and Type 2 PSSM.

<span class="mw-page-title-main">Myophosphorylase</span> Muscle enzyme involved in glycogen breakdown

Myophosphorylase or glycogen phosphorylase, muscle associated (PYGM) is the muscle isoform of the enzyme glycogen phosphorylase and is encoded by the PYGM gene. This enzyme helps break down glycogen into glucose-1-phosphate, so it can be used within the muscle cell. Mutations in this gene are associated with McArdle disease, a glycogen storage disease of muscle.

Glucan 1,4-α-glucosidase Enzyme that hydrolyses terminal α-1,4-D-glucose residues of polysaccharides

Glucan 1,4-α-glucosidase is an enzyme located on the brush border of the small intestine with systematic name 4-α-D-glucan glucohydrolase. It catalyses the following 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">Inborn errors of carbohydrate metabolism</span> Medical condition

Inborn errors of carbohydrate metabolism are inborn error of metabolism that affect the catabolism and anabolism of carbohydrates.

<span class="mw-page-title-main">Alpha glucan</span>

α-Glucans (alpha-glucans) are polysaccharides of D-glucose monomers linked with glycosidic bonds of the alpha form. α-Glucans use cofactors in a cofactor site in order to activate a glucan phosphorylase enzyme. This enzyme causes a reaction that transfers a glucosyl portion between orthophosphate and α-I,4-glucan. The position of the cofactors to the active sites on the enzyme are critical to the overall reaction rate thus, any alteration to the cofactor site leads to the disruption of the glucan binding site.

<span class="mw-page-title-main">Glucan 1,4-alpha-maltohydrolase</span>

Glucan 1,4-alpha-maltohydrolase is an enzyme with systematic name 4-alpha-D-glucan alpha-maltohydrolase. This enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">Neopullulanase</span>

Neopullulanase is an enzyme of the alpha-amylase family with systematic name pullulan 4-D-glucanohydrolase (panose-forming). This enzyme principally catalyses the following chemical reaction by cleaving pullulan's alpha-1,4-glucosidic bonds:

Glycogen phosphorylase, liver form (PYGL), also known as human liver glycogen phosphorylase (HLGP), is an enzyme that in humans is encoded by the PYGL gene on chromosome 14. This gene encodes a homodimeric protein that catalyses the cleavage of alpha-1,4-glucosidic bonds to release glucose-1-phosphate from liver glycogen stores. This protein switches from inactive phosphorylase B to active phosphorylase A by phosphorylation of serine residue 14. Activity of this enzyme is further regulated by multiple allosteric effectors and hormonal controls. Humans have three glycogen phosphorylase genes that encode distinct isozymes that are primarily expressed in liver, brain and muscle, respectively. The liver isozyme serves the glycemic demands of the body in general while the brain and muscle isozymes supply just those tissues. In glycogen storage disease type VI, also known as Hers disease, mutations in liver glycogen phosphorylase inhibit the conversion of glycogen to glucose and results in moderate hypoglycemia, mild ketosis, growth retardation and hepatomegaly. Alternative splicing results in multiple transcript variants encoding different isoforms [provided by RefSeq, Feb 2011].

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000114480 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022707 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 "Entrez Gene: glucan (1,4-alpha-), branching enzyme 1" . Retrieved 2011-08-30.
  6. ↑ Berg J (2012). Biochemistry (Seventh ed.). W.H. Freeman and Company. pp. 627–630.
  7. 1 2 "GBE1 glucan (1,4-alpha-), branching enzyme 1 [ Homo sapiens (human) ]". National Center for Biotechnology Information. US. National Library of Medicine.
  8. 1 2 "Glycogen Branching Enzyme; GBE1". Online Mendelian Inheritance in Man. Johns Hopkins University.
  9. 1 2 3 4 5 6 7 8 9 Genetics Home Reference. "GBE1". U.S. National Library of Medicine.
  10. 1 2 3 4 Thon VJ, Khalil M, Cannon JF (April 1993). "Isolation of human glycogen branching enzyme cDNAs by screening complementation in yeast". The Journal of Biological Chemistry. 268 (10): 7509–7513. doi: 10.1016/S0021-9258(18)53204-X . PMID   8463281.
  11. 1 2 3 Abad MC, Binderup K, Rios-Steiner J, Arni RK, Preiss J, Geiger JH (November 2002). "The X-ray crystallographic structure of Escherichia coli branching enzyme". The Journal of Biological Chemistry. 44. 277 (44): 42164–42170. doi: 10.1074/jbc.m205746200 . PMID   12196524.
  12. ↑ Pal K, Kumar S, Sharma S, Garg SK, Alam MS, Xu HE, et al. (July 2010). "Crystal structure of full-length Mycobacterium tuberculosis H37Rv glycogen branching enzyme: insights of N-terminal beta-sandwich in substrate specificity and enzymatic activity". The Journal of Biological Chemistry. 285 (27): 20897–20903. doi: 10.1074/jbc.M110.121707 . PMC   2898361 . PMID   20444687.
  13. ↑ Matsuura Y, Kusunoki M, Harada W, Kakudo M (March 1984). "Structure and possible catalytic residues of Taka-amylase A". Journal of Biochemistry. 95 (3): 697–702. doi: 10.1093/oxfordjournals.jbchem.a134659 . PMID   6609921.
  14. ↑ Buisson G, Duée E, Haser R, Payan F (December 1987). "Three dimensional structure of porcine pancreatic alpha-amylase at 2.9 A resolution. Role of calcium in structure and activity". The EMBO Journal. 6 (13): 3909–3916. doi:10.1002/j.1460-2075.1987.tb02731.x. PMC   553868 . PMID   3502087.
  15. ↑ Devillers CH, Piper ME, Ballicora MA, Preiss J (October 2003). "Characterization of the branching patterns of glycogen branching enzyme truncated on the N-terminus". Archives of Biochemistry and Biophysics. 418 (1): 34–38. doi:10.1016/S0003-9861(03)00341-2. PMID   13679080.
  16. ↑ Kuriki T, Stewart DC, Preiss J (November 1997). "Construction of chimeric enzymes out of maize endosperm branching enzymes I and II: activity and properties". The Journal of Biological Chemistry. 272 (46): 28999–29004. doi: 10.1074/jbc.272.46.28999 . PMID   9360973.
  17. ↑ Palomo M, Pijning T, Booiman T, Dobruchowska JM, van der Vlist J, Kralj S, et al. (February 2011). "Thermus thermophilus glycoside hydrolase family 57 branching enzyme: crystal structure, mechanism of action, and products formed". The Journal of Biological Chemistry. 286 (5): 3520–3530. doi: 10.1074/jbc.m110.179515 . PMC   3030357 . PMID   21097495.
  18. ↑ Santos CR, Tonoli CC, Trindade DM, Betzel C, Takata H, Kuriki T, et al. (February 2011). "Structural basis for branching-enzyme activity of glycoside hydrolase family 57: structure and stability studies of a novel branching enzyme from the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1". Proteins. 79 (2): 547–557. doi:10.1002/prot.22902. PMID   21104698. S2CID   25862890.
  19. ↑ Noguchi J, Chaen K, Vu NT, Akasaka T, Shimada H, Nakashima T, et al. (August 2011). "Crystal structure of the branching enzyme I (BEI) from Oryza sativa L with implications for catalysis and substrate binding". Glycobiology. 21 (8): 1108–1116. doi:10.1093/glycob/cwr049. PMID   21493662.
  20. ↑ Rose S (1999). The Chemistry of Life. Pelican Books. pp. 199–201.
  21. ↑ McKusick VA, Kniffin CL (May 2, 2016). "OMIM Entry 263570 - Polyglucosan body neuropathy, adult form". Online Mendelian Inheritance in Man. Johns Hopkins University. Retrieved 7 March 2017.
  22. ↑ Mingyi C (2011). "Glycogen Storages Diseases chapter of Molecular Pathology of Liver Diseases". In Monga SP (ed.). Molecular Pathology of Liver Diseases. Springer. pp. 677–682. ISBN   9781441971074.
  23. ↑ Bruno C, van Diggelen OP, Cassandrini D, Gimpelev M, Giuffrè B, Donati MA, et al. (September 2004). "Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis type IV)". Neurology. 63 (6): 1053–1058. doi:10.1212/01.wnl.0000138429.11433.0d. PMID   15452297. S2CID   7874969.
  24. 1 2 3 Klein C (1993). "Adult Polyglucosan Body Disease". GeneReviews. University of Washington, Seattle. PMID   20301758.
  25. ↑ Hussain A, Armistead J, Gushulak L, Kruck C, Pind S, Triggs-Raine B, et al. (September 2012). "The adult polyglucosan body disease mutation GBE1 c.1076A>C occurs at high frequency in persons of Ashkenazi Jewish background". Biochemical and Biophysical Research Communications. 426 (2): 286–288. doi:10.1016/j.bbrc.2012.08.089. PMID   22943850.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.