Glycogen branching enzyme

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glycogen branching enzyme
Identifiers
EC number 2.4.1.18
CAS number 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 / EGO
1,4-alpha-glucan branching enzyme
Identifiers
Symbol GBE1
Entrez 2632
HUGO 4180
OMIM 607839
RefSeq NM_000158
UniProt Q04446
Other data
Locus Chr. 3 p12

“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 a large number of terminal residues for rapid degradation. Branching also importantly increases the solubility and decreases the osmotic strength of glycogen.[1]

Function[edit]

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.[2]

Nomenclature[edit]

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, 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.

Structure[edit]

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.[3][4] 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.[3][5][6][7] 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.[3]

Glycogen binding enzymes in other organisms have also been crystallized and structurally determined, demonstrating both similarity and variation to GBE found in Escherichia coli.[8][9][10][11]

Genetic Location and Pathology[edit]

The official name of the gene encoding glycogen binding enzyme is “glucan (1,4-alpha-), branching enzyme 1” with an official gene symbol of GBE1.[12][13][14] 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.[12][13][14][15] The human GBE gene was also isolated by a function complementation of the Saccharomyces cerevisiae GBE deficiency.[15] From the isolated cDNA, the length of the gene was found to be approximately 3 kb.[15] Additionally, the coding sequence was found to comprise of 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.[15] 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).[14] 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.[14] Glycogen buildup leads to increased osmotic pressure resulting in cellular swelling and death.[14] The tissues most affected by this disease are the liver, heart, and neuromuscular system, areas with the greatest levels of glycogen accumulation.[14][16] Abnormal glycogen buildup in the liver interferes with liver functioning and can result in an enlarged liver and liver disease.[14][17] 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.[14] At least three mutations in the GBE1 gene have been found to cause another disease called adult polyglucosan body disease (APBD).[14][18] While in GSD IV GBE activity is undetectable or minimally detectable, APBD is characterized by reduced or even normal GBE activity.[18] 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.[18][19]

References[edit]

  1. ^ Berg, Jeremey (2012). Biochemistry Seventh Edition. W.H. Freeman and Company. pp. 627–630. 
  2. ^ Rose, Steven (1999). The Chemistry of LIfe. Pelican Books. pp. 199–201. 
  3. ^ a b c Abad, Marta; Binderup, Kim, Rios-Steiner, Jorge, Arni, Raghuvir, Preiss, Jack, Geiger, James (August 23, 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. 
  4. ^ Pal, Kuntal; Kumar, Shiva, Sharma, Shikha, Garg, Saurabh Kumar, Alam, Mohammad Suhail, Xu, H. Eric, Agrawal, Pushpa, Swaminathan, Kunchithapadam (May 5, 2010). "Crystal Structure of Full-length Mycobacterium tuberculosis H37Rv Glycogen Branching Enzyme INSIGHTS OF N-TERMINAL β-SANDWICH IN SUBSTRATE SPECIFICITY AND ENZYMATIC ACTIVITY". The Journal of Biological Chemistry 265: 20897–20903. 
  5. ^ Matsuura, Yoshiki; Kusunoki, Masami, Harada, Wakako, Kakudo, Masao (1984). "Structure and Possible Catalytic Residues of Taka-Amylase A". The Journal of Biochemistry 95 (3): 697–702. 
  6. ^ Buisson, G; Duee, E; Haser, R; Payan, F (December 20, 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. PMC 553868. PMID 3502087. 
  7. ^ Devillers, Claire; Piper, Mary, Ballicora, Miguel, Preiss, Jack (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. 
  8. ^ Kuriki, Takashi; Stewart, Douglas, Preiss, Jack (1997). "Construction of Chimeric Enzyme out of Maize Endosperm Branching Enzyme I and II: Activity and Properties". The Journal of Biological Chemistry 46: 28999–29004. 
  9. ^ Palomo, Marta; Pijning, Tjaard, Booiman, Thijs, Dobruchowska, Justyna, Van der Vlist, Jeroen, Kralj, Slavko, Planas, Antoni, Loos, Katja, Kamerling, Johannis, Dijkstra, Bauke, Van der Maarel, Marc, Dijkhuizen, Lubbert, Leemhuis, Hans (February 4, 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. 
  10. ^ Santos, Camila; Tonoli, Celisa, Trindade, Daniel, Betzel, Christian, Takata, Hiroki, Kuriki, Takashi, Kanai, Tamotsu, Imanaka, Tadayuki, Arni, Raghuvir, Murakami, Mario (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: 547–557. doi:10.1002/prot.22902. 
  11. ^ Nogushi, Junji; Chaen, Kimiko, Vu, Nhuan, Akasaka, Taiki, Shimada, Hiroaki, Nakashima, Takashi, Nishi, Aiko, Satoh, Hikaru, Omori, Toshiro, Kakuta, Yoshimuitsu, Makoto, Kimura (April 3, 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. 
  12. ^ a b National Center for Biotechnology Information. "GBE1 glucan (1,4-alpha-), branching enzyme 1 [ Homo sapiens (human) ]". US. National Library of Medicine. 
  13. ^ a b Online Mendelian Inheritance in Man. "Glycogen Branching Enzyme; GBE1". Johns Hopkins University. 
  14. ^ a b c d e f g h i Genetics Home Reference. "GBE1". U.S. National Library of Medicine. 
  15. ^ a b c d Thon, Vicki; Khalil, Miriam, Cannon, John (1993). "Isolation of Human Glycogen Branching Enzyme cDNAs by Screening Complementation in Yeast". The Journal of Biological Chemistry 268 (10): 7509–7513. 
  16. ^ Mingyi, Chen (2011). Glycogen Storages Diseases chapter of Molecular Pathology of Liver Diseases. Springer. pp. 677–682. 
  17. ^ Bruno, C.; Van Diggelen, O.P., Cassandrini, D., Gimpelev, M., Gluffre B., Donati, M.A., Introvini, P., Alegria, A., Assereto, S., Morandi, L., Mora, M., Tonoli, E., Mascelli, S., Traverso, M., Pasquini, E., Bado, M., Vilarinho, L., Van Noort, G., Mosca, F., DiMauro, S., Zara, F., Minetti, C. (September 28, 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. 
  18. ^ a b c Klein, Christopher. "Adult Polyglucosan Body Disease". 
  19. ^ Hussain, Abrar; Armistead, Joy, Gushulak, Lara, Kruck, Christa, Pind, Steven, Triggs-Raine, Barbara, Natowicz, Marvin (September 2002). "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: 286–288. doi:10.1016/j.bbrc.2012.08.089. 
  • Barker SA, Bourne E and Peat S (Lond.). "The enzymic synthesis and degradation of starch. Part IV. The purification and storage of the Q-enzyme of the potato". J. Chem. Soc.: 1705–1711. doi:10.1039/jr9490001705. 
  • Baum H and Gilbert GA (1953). "A simple method for the preparation of crystalline potato phosphorylase and Q-enzyme". Nature 171 (4361): 983–984. doi:10.1038/171983a0. PMID 13063502. 
  • Hehre EJ (1951). Enzymic Synthesis of Polysaccharides: a Biological type of Polymerization. "Advances in Enzymology and Related Areas of Molecular Biology". Adv. Enzymol. Relat. Subj. Biochem. Advances in Enzymology - and Related Areas of Molecular Biology 11: 297–337. doi:10.1002/9780470122563.ch6. ISBN 978-0-470-12256-3. 
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