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 → Glycogen and Starch Biosynthesis|
Glycogen is a highly branched glucose polymer that serves as a form of energy storage in animals and fungi. It resembles plant-produced starch and is sometimes called "animal starch".
Glycogen is formed of small chains of 8 to 12 glucose molecules linked together by α (1->4) bonds. These small chains, also known as maltodextrins, are in turn linked together by α (1->6) bonds. The α-1,4 linkages make up approximately 95% of the total molecule. The α-1,6 branches accounts for 7-10% of the linkages and are evenly distributed within the glycogen particle.
Since each chain (with the exception of the outer unbranched chains) supports two branches, glycogen particles grow spherically by adding tiers (a tier corresponds to the spherical space separating two consecutive branches from all chains located at similar distance from the center of the particle). Mathematical modelling predicts a maximal value for the particle size above which further growth is impossible as there would not be sufficient space for interaction of the chains with the catalytic sites of glycogen metabolism enzymes. This generates a particle consisting of 12 tiers corresponding to a 42 nm maximal diameter including 55 000 glucose residues. 36% of this total number rests in the outer (unbranched) shell and is thus readily accessible to glycogen catabolism without debranching [Shearer02].
Although glycogen and starch are two distinct physical states of the same type of storage polysaccharide, starch is solid semi-crystalline while glycogen particles are entirely hydrosoluble [Ball11].
Glucose is polymerized within the polysaccharides thanks to its activation in the form of a nucleotide-sugar through the action of NDP-glucose pyrophosphorylase. All eukaryotes known synthesize glycogen from UDP-α-D-glucose while all Gram-negative glycogen accumulating bacteria use ADP-α-D-glucose (see glycogen biosynthesis II (from UDP-D-Glucose) and glycogen biosynthesis I (from ADP-D-Glucose)).
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.
Initiation of glycogen biosynthesis in mammals is mediated by the enzyme glycogenin (EC 22.214.171.124). 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].
Ball11: Ball S, Colleoni C, Cenci U, Raj JN, Tirtiaux C (2011). "The evolution of glycogen and starch metabolism in eukaryotes gives molecular clues to understand the establishment of plastid endosymbiosis." J Exp Bot 62(6);1775-801. PMID: 21220783
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
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