Metabolic Modeling Tutorial
registration ends
Sat Mar 7th, 2015
Metabolic Modeling Tutorial
registration ends
Sat Mar 7th, 2015
Metabolic Modeling Tutorial
registration ends
Sat Mar 7th, 2015
Metabolic Modeling Tutorial
registration ends
Sat Mar 7th, 2015
Metabolic Modeling Tutorial
registration ends
Sat Mar 7th, 2015

MetaCyc Pathway: glycogen biosynthesis II (from UDP-D-Glucose)

Enzyme View:

Note: a dashed line (without arrowheads) between two compound names is meant to imply that the two names are just different instantiations of the same compound -- i.e. one may be a specific name and the other a general name, or they may both represent the same compound in different stages of a polymerization-type pathway. This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Biosynthesis Carbohydrates Biosynthesis Polysaccharides Biosynthesis Glucogen and Starch Biosynthesis

Some taxa known to possess this pathway include ? : Homo sapiens , Neurospora crassa , Oryctolagus cuniculus , Rattus norvegicus , Saccharomyces cerevisiae

Expected Taxonomic Range: Fungi , Metazoa

General Background

Glycogen and starch, megadalton-sized glucose polymers, are the major reservoir of readily available energy and carbon compounds in most living organisms, ranging from the archaea, eubacteria and yeasts to the higher eukaryotes, including plants and animals. Only parasites seem to lack enzymes for the metabolism of these compounds [Henrissat02].

The linkages between the glucose units in glycogen are comprised of approximately 90% α-1,4 linkages, with the remainder being α-1,6 branch glucosyl linkages. The average chain length is about 12 to 14 glucose units.

A key enzyme in the biosynthetic pathway is glycogen (or starch) synthase. Glycogen and starch synthases are classified in two large and distinct famillies: the mammalian and yeast enzymes utilize UDP-α-D-glucose as the glucosyl group donor (see glycogen biosynthesis II (from UDP-D-Glucose)), while bacterial and plant enzymes prefer ADP-α-D-glucose (see glycogen biosynthesis I (from ADP-D-Glucose) and starch biosynthesis).

About This Pathway

In mammals glycogen is synthesized and stored primarily in liver and muscle cells [Peng93, Katz97]. Glycogen metabolism is a major component of whole-body glucose metabolism, and defective glycogen storage is associated with several diseases, including type 2 diabetes.

The precursor for glycogen synthesis in mammals is UDP-α-D-glucose, which is produced from α-D-glucose 1-phosphate by the enzyme UDP-glucose pyrophosphorylase.

Initiation of glycogen biosynthesis in mammals is mediated by the enzyme glycogenin (EC This unusual enzyme catalyzes two reactions: first, it transfers one glucose unit from UDP-glucose to form an oligosaccharide covalently attached to itself at a tyrosine residue (Tyr194). Next it catalyzes the addition of additional glucose units to the first one by α-1,4-glucosidic linkages, forming a glycogen primer [Lomako04, Gibbons02].

The mammalian glycogen synthase, which is a homotetramer of 85 kDa subunits, attaches to the glucosylated glycogenin complex, and catalyzes the transfer of the glucose moiety of additional UDP-α-D-glucose molecules by α-1,4-glucosidic linkage, extending the glycogen chain further.

During this elongation process, branched α-1,6-glucosidic linkages are formed by the 1,4-α-glucan branching enzyme, which cuts groups of ~6 glucose units from the end of the chains, and reattaches them by α-1,6-linkages, forming branched points.

This process continues, forming a complex termed proglycogen, which is about 400 kDa. At this point, a different glycogen synthase, with a lower affinity for UDP-α-D-glucose, replaces the previous synthase, and along with the branching enzyme, catalyzes the synthesis of a final macroglycogen polymer, which is about 10,000 kDa [Alonso95].

Variants: glycogen biosynthesis I (from ADP-D-Glucose) , starch biosynthesis

Created 12-Dec-2005 by Caspi R , SRI International


Alonso95: Alonso MD, Lomako J, Lomako WM, Whelan WJ (1995). "A new look at the biogenesis of glycogen." FASEB J 9(12);1126-37. PMID: 7672505

Gibbons02: Gibbons BJ, Roach PJ, Hurley TD (2002). "Crystal structure of the autocatalytic initiator of glycogen biosynthesis, glycogenin." J Mol Biol 319(2);463-77. PMID: 12051921

Henrissat02: Henrissat B, Deleury E, Coutinho PM (2002). "Glycogen metabolism loss: a common marker of parasitic behaviour in bacteria?." Trends Genet 18(9);437-40. PMID: 12175798

Katz97: Katz A (1997). "Differential responses of glycogen synthase to ischaemia and ischaemic contraction in human skeletal muscle." Exp Physiol 82(1);203-11. PMID: 9023518

Lomako04: Lomako J, Lomako WM, Whelan WJ (2004). "Glycogenin: the primer for mammalian and yeast glycogen synthesis." Biochim Biophys Acta 1673(1-2);45-55. PMID: 15238248

Peng93: Peng HL, Chang HY (1993). "Cloning of a human liver UDP-glucose pyrophosphorylase cDNA by complementation of the bacterial galU mutation." FEBS Lett 329(1-2);153-8. PMID: 8354390

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Bao96: Bao Y, Kishnani P, Wu JY, Chen YT (1996). "Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen-branching enzyme gene." J Clin Invest 97(4);941-8. PMID: 8613547

Barbetti96: Barbetti F, Rocchi M, Bossolasco M, Cordera R, Sbraccia P, Finelli P, Consalez GG (1996). "The human skeletal muscle glycogenin gene: cDNA, tissue expression and chromosomal localization." Biochem Biophys Res Commun 220(1);72-7. PMID: 8602861

Browner89: Browner MF, Nakano K, Bang AG, Fletterick RJ (1989). "Human muscle glycogen synthase cDNA sequence: a negatively charged protein with an asymmetric charge distribution." Proc Natl Acad Sci U S A 86(5);1443-7. PMID: 2493642

Buschiazzo04: Buschiazzo A, Ugalde JE, Guerin ME, Shepard W, Ugalde RA, Alzari PM (2004). "Crystal structure of glycogen synthase: homologous enzymes catalyze glycogen synthesis and degradation." EMBO J 23(16);3196-205. PMID: 15272305

Cao93: Cao Y, Mahrenholz AM, DePaoli-Roach AA, Roach PJ (1993). "Characterization of rabbit skeletal muscle glycogenin. Tyrosine 194 is essential for function." J Biol Chem 268(20);14687-93. PMID: 8325847

Gibson71: Gibson WB, Illingsworth B, Brown DH (1971). "Studies of glycogen branching enzyme. Preparation and properties of -1,4-glucan- -1,4-glucan 6-glycosyltransferase and its action on the characteristic polysaccharide of the liver of children with Type IV glycogen storage disease." Biochemistry 10(23);4253-62. PMID: 5288588

Larner53: Larner, J. (1953). "The action of branching enzymes on outer chains of glycogen." J Biol Chem 202(2);491-503. PMID: 13061474

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lazarowski03: Lazarowski ER, Shea DA, Boucher RC, Harden TK (2003). "Release of cellular UDP-glucose as a potential extracellular signaling molecule." Mol Pharmacol 63(5);1190-7. PMID: 12695547

Mu97: Mu J, Skurat AV, Roach PJ (1997). "Glycogenin-2, a novel self-glucosylating protein involved in liver glycogen biosynthesis." J Biol Chem 272(44);27589-97. PMID: 9346895

Mu98: Mu J, Roach PJ (1998). "Characterization of human glycogenin-2, a self-glucosylating initiator of liver glycogen metabolism." J Biol Chem 273(52);34850-6. PMID: 9857012

Nuttall94: Nuttall FQ, Gannon MC, Bai G, Lee EY (1994). "Primary structure of human liver glycogen synthase deduced by cDNA cloning." Arch Biochem Biophys 311(2);443-9. PMID: 8203908

Okubo88: Okubo M, Bogardus C, Lillioja S, Mott DM (1988). "Glucose-6-phosphate stimulation of human muscle glycogen synthase phosphatase." Metabolism 37(12);1171-6. PMID: 2848177

Orho95: Orho M, Nikula-Ijas P, Schalin-Jantti C, Permutt MA, Groop LC (1995). "Isolation and characterization of the human muscle glycogen synthase gene." Diabetes 44(9);1099-105. PMID: 7657035

Plesner74: Plesner L, Plesner IW, Esmann V (1974). "Kinetic mechanism of glycogen synthase D from human polymorphonuclear leukocytes." J Biol Chem 249(4);1119-25. PMID: 4205314

Roach76: Roach PJ, Takeda Y, Larner J (1976). "Rabbit skeletal muscle glycogen synthase. I. Relationship between phosphorylation state and kinetic properties." J Biol Chem 251(7);1913-9. PMID: 818081

Solling77: Solling H, Esmann V (1977). "Purification and properties of glycogen synthase I from human leukocytes." Eur J Biochem 81(1);119-28. PMID: 412671

Thon93: Thon VJ, Khalil M, Cannon JF (1993). "Isolation of human glycogen branching enzyme cDNAs by screening complementation in yeast." J Biol Chem 268(10);7509-13. PMID: 8463281

Verhue66: Verhue W, Hers HG (1966). "A study of the reaction catalysed by the liver branching enzyme." Biochem J 99(1);222-7. PMID: 4290551

Westphal92: Westphal SA, Nuttall FQ (1992). "Comparative characterization of human and rat liver glycogen synthase." Arch Biochem Biophys 292(2);479-86. PMID: 1731614

Showing only 20 references. To show more, press the button "Show all references".

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Wed Mar 4, 2015, biocyc12.