Glycogen phosphorylase, liver type (PYGL)

Glycogen phosphorylase, liver type (PYGL) is the hepatic isoform of glycogen phosphorylase, an enzyme that catalyzes the rate-limiting step of glycogenolysis by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bonds of glycogen.[1][3] This enzyme is essential for maintaining blood glucose levels during fasting periods and low glucose availability by breaking down hepatic glycogen stores and releasing glucose to peripheral tissues.[2] The liver isoform functions as a "glucose sensor," remaining active unless allosterically inhibited by high blood glucose concentrations, which signal sufficient glucose availability.[1][2] Mutations in the PYGL gene cause Hers' disease (glycogen storage disease type VI), characterized by mild hypoglycemia and variable symptoms.[1] Inhibition of liver glycogen phosphorylase has been proposed as a therapeutic strategy for type 2 diabetes, as elevated hepatic glucose production contributes to hyperglycemia in diabetic patients.[1] Experimental glucose-mimetic inhibitors have shown promise, with potential for selective targeting of this enzyme to modulate glucose homeostasis.[1]

Other names

Liver glycogen phosphorylaseHepatic glycogen phosphorylasePhosphorylase a (active form)Phosphorylase b (inactive form)Human liver glycogen phosphorylase (HLGP)

Inhibition of hepatic glucose output (proposed therapeutic approach for type 2 diabetes); Allosteric inhibition by glucose, which inactivates the enzyme; Regulation through reversible phosphorylation and allosteric effects