Glycogenolysis

Glycogenolysis is the metabolic process by which glycogen, the stored polymer of glucose, is broken down to make its glucose units available for metabolism. It occurs mainly in the cytosol and is especially important in the liver and skeletal muscle, the body's major glycogen stores. The principal product released directly from glycogen is glucose-1-phosphate rather than free glucose .^1,2

The key enzyme glycogen phosphorylase removes glucose residues from the nonreducing ends of glycogen by cleaving α(1→4) glycosidic bonds, releasing glucose-1-phosphate. When degradation approaches an α(1→6) branch point, the glycogen debranching enzyme rearranges the chain and removes the branch, releasing a small amount of free glucose. Glucose-1-phosphate is then converted by phosphoglucomutase to glucose-6-phosphate .^1,2

The fate of glucose-6-phosphate differs between tissues. Liver cells contain glucose-6-phosphatase, which can convert glucose-6-phosphate to free glucose for release into the bloodstream, allowing liver glycogenolysis to help maintain blood glucose during fasting. Skeletal muscle lacks significant glucose-6-phosphatase activity, so glucose derived from muscle glycogen is used primarily within the muscle, particularly through glycolysis to support energy production during contraction .^1,2

Glycogenolysis is regulated according to metabolic demand. Glucagon promotes the process in the liver, while epinephrine can stimulate glycogen breakdown in both liver and muscle. In contracting skeletal muscle, calcium and signals associated with increased energy demand can also promote glycogen breakdown. Glycogenolysis is distinct from glycolysis, which metabolizes glucose or glucose-6-phosphate further, and from gluconeogenesis, which synthesizes new glucose from noncarbohydrate precursors .^1,2