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 is quite stable. The protonated oxygen now represents a good leaving group, and the glycogen chain is separated from the terminal glycogen in an S1 fashion, resulting in the formation of a glucose molecule with a secondary carbocation at the 1 position. Finally, the deprotonated inorganic phosphate acts as a nucleophile and bonds with the carbocation, resulting in the formation of glucose-1-phosphate and a glycogen chain shortened by one glucose molecule. There is also an alternative proposed mechanism involving a positively charged oxygen in a half-chair conformation. The glycogen phosphorylase monomer is a large protein, composed of 842 amino acids