Phosphorylases

Phosphorylases are enzymes that catalyze the phosphorolytic cleavage of alpha-1,4 glycosidic bonds in glucose polymers such as glycogen and starch. Using inorganic phosphate, they release glucose-1-phosphate from the nonreducing ends of the polymer, enabling mobilization of stored carbohydrate without generating free glucose.

Two major groups are recognized: glycogen phosphorylases, which act on animal glycogen (and on starch in plants), and starch phosphorylases, which primarily function in plant metabolism. In mammals, muscle and liver express distinct glycogen phosphorylase isozymes with tissue-specific regulatory properties; plants contain plastidial and cytosolic phosphorylases.

Activity is controlled by both allosteric effectors and covalent modification. Phosphorylation by phosphorylase kinase converts the less active phosphorylase b to the more active phosphorylase a; in liver, glucose acts as an allosteric inhibitor of phosphorylase a. In muscle, AMP strongly activates phosphorylase b. Dephosphorylation terminates activity. The debranching enzyme is needed for complete glycogen breakdown beyond alpha-1,6 linkages.

During fasting or exercise, hormonal signals promote phosphorylation and glycogen breakdown to supply glucose-1-phosphate for glycolysis; in plants, starch reserves are mobilized in the dark via plastidial phosphorylases.

Defects in glycogen phosphorylase cause glycogen storage diseases, such as McArdle disease (muscle, PYGM deficiency) and Hers disease (liver, PYGL deficiency). Symptoms include exercise intolerance, cramps, and hypoglycemia. Phosphorylases are essential for rapid glucose supply during periods of energy demand.