glycogenolysis

Glycogenolysis is the metabolic pathway by which glycogen is broken down to glucose. In glycogen, glucose units are linked mainly by α-1,4-glycosidic bonds with branch points connected by α-1,6 bonds. The initial step is catalyzed by glycogen phosphorylase, which cleaves glucose units as glucose-1-phosphate from the nonreducing ends until four residues remain before a branch. A debranching enzyme then transfers a block of three residues and hydrolyzes the α-1,6 linkage, releasing one free glucose. Glucose-1-phosphate is converted to glucose-6-phosphate by phosphoglucomutase. In liver, glucose-6-phosphate is dephosphorylated by glucose-6-phosphatase to produce free glucose that can be released into the bloodstream; in muscle, glucose-6-phosphate is primarily used for glycolysis to supply ATP for contraction.

Regulation: Glycogenolysis is stimulated by hormones such as glucagon (liver) and epinephrine (liver and muscle) acting through cAMP and protein kinase A, which activate glycogen phosphorylase kinase and convert glycogen phosphorylase to the active form. Insulin antagonizes this pathway by activating phosphatases that inactivate glycogen phosphorylase. In muscle, Ca2+ released during contraction also activates glycogen phosphorylase kinase. Allosteric regulation includes activation of glycogen phosphorylase by AMP in muscle and inhibition by glucose in liver.

Physiological role: Glycogenolysis maintains blood glucose during fasting and provides rapid energy during exercise. Defects in the enzymes of glycogenolysis can contribute to glycogen storage diseases, with clinical features such as hypoglycemia, exercise intolerance, or hepatomegaly depending on the tissue affected.