Glycogen phosphorylase (muscle form) (GPb)

Glycogen phosphorylase b is the dephosphorylated, less active form of glycogen phosphorylase found predominantly in skeletal muscle. It catalyzes the rate-limiting step of glycogen breakdown by removing glucose residues from glycogen as glucose-1-phosphate, a key process for mobilizing energy during muscle contraction[1][3][8]. The enzyme is allosterically regulated by various effectors such as adenosine monophosphate (AMP) and is converted to its more active form (glycogen phosphorylase a) by phosphorylation of a key serine residue (Ser14)[4][3][8]. Glycogen phosphorylase has been studied extensively as a drug target for diabetes and metabolic disorders, with several small-molecule inhibitors developed to limit unwanted glucose production[6]. Deficiency or genetic mutations of the muscle isoform (coded by the PYGM gene) cause McArdle disease, a rare glycogen storage disorder. Recent structural studies reveal multiple allosteric and catalytic regulatory sites, making the enzyme amenable to pharmacological modulation[6][1]. Key therapeutic challenges involve balancing inhibition to avoid hypoglycemia and ensuring specificity among isoforms.

Other names

Glycogen phosphorylase bMuscle glycogen phosphorylasePYGM (gene symbol, human muscle isozyme)GPb (abbreviation)

Inhibition of glycogen phosphorylase reduces glycogen breakdown, lowering glucose output from tissues (particularly muscle and liver). Allosteric inhibition stabilizes the less active "T state" of the enzyme. Catalytic site inhibitors directly block glycogen-binding and catalysis.