Myophosphorylase

Myophosphorylase, also known as muscle glycogen phosphorylase, is an enzyme that catalyzes the initial step of glycogen breakdown in skeletal muscle. It cleaves glucose units from glycogen as glucose-1-phosphate, which is then converted to glucose-6-phosphate and funneled into glycolysis to meet muscular energy demands. The muscle isoform is encoded by the PYGM gene and is distinct from liver (PYGL) and brain (PYGB) forms.

In human muscle, glycogen phosphorylase exists in phosphorylated (active, form A) and dephosphorylated (less active, form B) states. Activation occurs by phosphorylation through phosphorylase kinase, which is stimulated by Ca2+ released during muscle contraction and by hormonal signaling that elevates cAMP. Allosteric regulation complements this: AMP activates the enzyme, whereas ATP and glucose-6-phosphate inhibit its activity. The enzyme’s activity integrates neural, hormonal, and energetic cues to meet rapid energy needs during exercise.

Clinical relevance arises from mutations in PYGM causing McArdle disease (glycogen storage disease type V). Affected individuals experience exercise-induced muscle cramps, weakness, and myoglobinuria following strenuous activity, with a characteristic “second wind” phenomenon as alternative energy sources are recruited. Blood lactate levels during exercise are often blunted due to impaired glycogenolysis in muscle. Diagnosis combines clinical assessment, genetic testing for PYGM variants, and measurement of myophosphorylase activity in muscle fibers. Management emphasizes regular, moderate exercise and dietary strategies to maintain energy supply during activity.