Glycogen phosphorylase, muscle form (PYGM) (PYGM)

Glycogen phosphorylase, muscle form (PYGM) is a dimeric allosteric enzyme that catalyzes the rate-limiting step of glycogenolysis in skeletal muscle, releasing glucose-1-phosphate from stored glycogen to support energy metabolism during muscle contraction and exercise. The enzyme is a model system for understanding covalent enzyme regulation, operating through reversible phosphorylation at serine 14 and allosteric activation by adenosine monophosphate (AMP), which signals energy deficit. The enzyme requires pyridoxal-5'-phosphate (vitamin B6-derived cofactor) for catalytic activity and undergoes dynamic conformational changes between inactive (T state) and active (R state) forms in response to cellular energy status and hormonal signals including epinephrine and glucagon. Mutations in the PYGM gene cause glycogen storage disease type V (McArdle's disease), a metabolic disorder characterized by severe exercise intolerance, muscle pain, and weakness due to impaired glycogen mobilization. While extensively studied as a prototype for allosteric enzyme regulation, muscle glycogen phosphorylase remains an underexplored therapeutic target for pharmacological intervention in metabolic diseases.

Other names

Muscle glycogen phosphorylasePhosphorylase, muscle typeGlycogen phosphorylase isoform PYGM

Glycogen phosphorylase catalyzes the phosphorolysis of glycogen, cleaving alpha-1,4-glycosidic bonds to release glucose-1-phosphate. Its activity is primarily regulated by covalent modification (phosphorylation of Ser14 by phosphorylase kinase, triggered by hormonal signals like epinephrine and glucagon via cAMP pathways) and allosteric regulation. Allosteric activators such as AMP shift the enzyme to its active (R) state, while inhibitors like ATP and glucose-6-phosphate stabilize the inactive (T) state. Insulin inhibits glycogenolysis by decreasing cAMP levels, thereby reducing phosphorylase activation.