Glycogen phosphorylase, muscle isoform (PYGM)

Glycogen phosphorylase, muscle isoform (PYGM), is a key enzyme responsible for catalyzing the rate-limiting step in glycogenolysis: the phosphorolytic cleavage of glycogen to release glucose-1-phosphate. PYGM is predominately expressed in skeletal muscle but can also be found in other tissues, including the brain and lymphoid tissue. Its primary function is to supply energy rapidly during muscle contraction by mobilizing stored glycogen. It is regulated allosterically by AMP, ATP, and reversible phosphorylation at the Ser14 site, which switches the enzyme between active (phosphorylase a) and less active (phosphorylase b) forms. Mutations or deficiencies in PYGM cause McArdle disease (glycogen storage disease type V), characterized by exercise intolerance and muscle weakness. PYGM is implicated in several additional processes, including insulin signaling, immune response, cancer metabolism, and more, making it a potential therapeutic target for metabolic and neoplastic diseases[1][2][5][6].

Other names

Muscle glycogen phosphorylaseMyophosphorylaseGlycogen phosphorylase, muscle form

Inhibition of PYGM activity reduces glycogenolysis, decreasing the availability of glucose-1-phosphate from glycogen breakdown[2][5]. Inhibitors may block the enzyme's catalytic site or allosteric regulatory sites, impacting glucose release in muscle and potentially modulating metabolic pathways relevant for disease (e.g., cancer, metabolic disorders)[4].