UDP glycogen synthase
|Muscle glycogen synthase|
|Properties of human protein|
|Mass / length primary structure||737 amino acids|
|EC, category||glycosyl transferase,|
|Response type||Transfer of a glycosyl residue|
|Substrate||UDP-glucose + (1,4-α-D-glycosyl) n|
|Products||UDP + (1,4-α-D-glycosyl) n + 1|
|Parent taxon||Bilateria , Fungi|
|Liver glycogen synthase|
|Properties of human protein|
|Mass / length primary structure||701 amino acids|
The UDP-glycogen synthase (Gen: GYS ) is occurring in humans, animals and fungi glycogen synthase , an enzyme that for the construction of glycogen in metabolism is essential. Two isoforms are known, muscle glycogen synthase (gene: GYS1 ) and liver glycogen synthase ( GYS2 ). Mutations in the GYS genes can cause hereditary glycogen synthase deficiency and thus the very rare type 0 glycogen storage disease.
The main task of this regulated key enzyme of the glycogen metabolism is the polymerization of glucose in an α-1-4- glycosidic bond . This happens in the penultimate step of glycogen synthesis. With the splitting off of UDP, UDP-glucose (formed from UTP and glucose) is attached at the end to existing glycogen chains. The latter are a prerequisite for the reaction and are provided by initiation steps by the glycogenin (“priming glucosyltransferase”). Polymerization of free glucose that is not fixed to glycogenin chains does not take place.
Regulation through phosphorylation
The regulation of the glycogen synthase takes place, as with almost all important key enzymes of the metabolism , by phosphorylation and dephosphorylation . In the case of glycogen synthase, this occurs through the insulin / glucagon level, which, via a G-protein cascade, results in the provision of a second messenger . This activates the corresponding kinases or phosphatases which lead to the phosphorylation or dephosphorylation of enzymes . The following applies here: Phosphorylation by kinases leads to limited enzyme activity and dephosphorylation by phosphatases leads to complete enzyme activity.
The specific individual reactions are: Insulin deactivates glycogen synthase kinase 3 , which phosphorylates glycogen synthase in the resting state. It is dephosphorylated by protein phosphatase 1 (PP1). It is still unclear to what extent this PP1 activity is influenced by insulin. Glucagon, on the other hand, activates protein kinase A , which phosphorylates glycogen synthase.
The glycogen synthase is not completely inactivated in its phosphorylated form. Rather, it has a concentration-dependent activity. It is partially activated by a high concentration of glucose-6-phosphate .
- UniProt P54840
- Roach PJ, Takeda Y, Larner J: Rabbit skeletal muscle glycogen synthase. I. Relationship between phosphorylation state and kinetic properties . In: J. Biol. Chem. . 251, No. 7, April 1976, pp. 1913-9. PMID 818081 .
- Frame S, Cohen P: GSK3 takes center stage more than 20 years after its discovery . (PDF) In: Biochem. J. . 359, No. Pt 1, October 2001, pp. 1-16. PMID 11563964 . PMC 1222116 (free full text).
- Ceulemans H, Bollen M: Functional diversity of protein phosphatase-1, a cellular economizer and reset button . In: Physiol. Rev. . 84, No. 1, January 2004, pp. 1-39. doi : 10.1152 / physrev.00013.2003 . PMID 14715909 .
- Delibegovic M, Armstrong CG, Dobbie L, Watt PW, Smith AJ, Cohen PT: Disruption of the striated muscle glycogen targeting subunit PPP1R3A of protein phosphatase 1 leads to increased weight gain, fat deposition, and development of insulin resistance . In: Diabetes . 52, No. 3, March 2003, pp. 596-604. PMID 12606498 .
- Suzuki Y, Lanner C, Kim JH, et al : Insulin control of glycogen metabolism in knockout mice lacking the muscle-specific protein phosphatase PP1G / RGL . In: Mol. Cell. Biol . 21, No. 8, April 2001, pp. 2683-94. doi : 10.1128 / MCB.21.8.2683-2694.2001 . PMID 11283248 . PMC 86899 (free full text).