Glycogen phosphorylase In the liver, glucagon activates another G-protein-linked receptor that triggers a different cascade, resulting in the activation of Phospholipase C (PLC). PLC indirectly causes the release of calcium from the hepatocytes' endoplasmic reticulum into the cytosol. The increased calcium availability binds to the calmodulin subunit and activates glycogen phosphorylase kinase. Glycogen phosphorylase kinase activates glycogen phosphorylase in the same manner mentioned previously. Glycogen phosphorylase b is not always inactive in muscle, as it can be activated allosterically by AMP. An increase in AMP concentration, which occurs during strenuous exercise, signals energy demand. AMP activates glycogen phosphorylase b by changing its
Glycogen phosphorylase the subunit interface that is not present in the rabbit muscle glycogen phosphorylase (RMGP) normally used in studies. This site was not sensitive to the same inhibitors as those at the AMP allosteric site, and most success has been had synthesizing new inhibitors that mimic the structure of glucose, since glucose-6-phosphate is a known inhibitor of HLGP and stabilizes the less active T-state. These glucose derivatives have had some success in inhibiting HLGP, with predicted Ki values as low as 0.016 mM. Mutations in the muscle isoform of glycogen phosphorylase (PYGM) are associated with glycogen storage disease type V (GSD