Glycogen phosphorylase the site at which the enzyme binds to glycogen granules before initiating cleavage of terminal glucose molecules. In fact, 70% of dimeric phosphorylase in the cell exists as bound to glycogen granules rather than free floating. The inhibition of glycogen phosphorylase has been proposed as one method for treating type 2 diabetes. Since glucose production in the liver has been shown to increase in type 2 diabetes patients, inhibiting the release of glucose from the liver’s glycogen’s supplies appears to be a valid approach. The cloning of the human liver glycogen phosphorylase (HLGP) revealed a new allosteric binding site near
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