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|
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.
Initiation of glycogen biosynthesis in mammals is mediated by the enzyme glycogenin (EC 188.8.131.52). 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].
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
Browner89a: 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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