Regulation
The reaction is highly regulated by allosteric effectors such as glucose-6-phosphate, by phosphorylation reactions, and indirectly triggered by the hormone insulin, which is secreted by the pancreas. Phosphorylation of glycogen synthase decreases its activity. The enzyme also cleaves the ester bond between the C1 position of glucose and the pyrophosphate of UDP itself.
The control of glycogen synthase is a key step in regulating glycogen metabolism and glucose storage. Glycogen synthase is directly regulated by glycogen synthase kinase 3 (GSK-3), AMPK and protein kinase A (PKA). Each of these protein kinases lead to phosphorylated and catalytically inactive glycogen synthase. The phosphorylation sites of glycogen synthase are summarized below.
| Name | Phosphorylation Site | Kinase | Reference(s) |
|---|---|---|---|
| Site 1a | PKA | , | |
| Site 1b | PKA | , | |
| Site 2 | Serine 7 | AMPK | , |
| Site 2a | Serine 10 | CK2 | |
| Site 3a | Serine 641 | GSK3 | |
| Site 3b | Serine 645 | GSK3 | |
| Site 3c | Serine 649 | GSK3 | |
| Site 3d | Serine 653 | GSK3 | |
| Site 4 | Serine 727 |
For enzymes in the GT3 family, these regulatory kinases inactivate glycogen synthase by phosphorylating it at the N-terminal of the 25th residue and the C-terminal of the 120th residue. Glycogen synthase is also regulated by protein phosphatase 1 (PP1), which activates glycogen synthase via dephosphorylation. PP1 is targeted to the glycogen pellet by four targeting subunits, GM, GL, PTG and R6. These regulatory enzymes are regulated by insulin and glucagon signaling pathways.
Read more about this topic: Glycogen Synthase
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