glycogenolysis, process by which glycogen, the primary carbohydrate stored in the liver and muscle cells of animals, is broken down into glucose to provide immediate energy and to maintain blood glucose levels during fasting. Glycogenolysis occurs primarily in the liver and is stimulated by the hormones glucagon and epinephrine (adrenaline).

When blood glucose levels fall, as during fasting, there is an increase in glucagon secretion from the pancreas. That increase is accompanied by a concomitant decrease in insulin secretion, because the actions of insulin, which are aimed at increasing the storage of glucose in the form of glycogen in cells, oppose the actions of glucagon. Following secretion, glucagon travels to the liver, where it stimulates glycogenolysis.

The vast majority of glucose that is released from glycogen comes from glucose-1-phosphate, which is formed when the enzyme glycogen phosphorylase catalyzes the breakdown of the glycogen polymer. In the liver, kidneys, and intestines, glucose-1-phosphate is converted (reversibly) to glucose-6-phosphate by the enzyme phosphoglucomutase. Those tissues also house the enzyme glucose-6-phosphatase, which converts glucose-6-phosphate into free glucose that is secreted into the blood, thereby restoring blood glucose levels to normal. Glucose-6-phosphate is also taken up by muscle cells, where it enters glycolysis (the set of reactions that breaks down glucose to capture and store energy in the form of adenosine triphosphate, or ATP). Small amounts of free glucose also are produced during glycogenolysis through the activity of glycogen debranching enzyme, which completes the breakdown of glycogen by accessing branching points in the polymer.

Epinephrine, similar to glucagon, stimulates glycogenolysis in the liver, resulting in the raising of the level of blood glucose. However, that process is generally initiated by the fight-or-flight response, as opposed to the physiological drop in blood glucose levels that stimulates glucagon secretion. Compare glycogenesis.

Various rare inherited diseases of glycogen storage produce abnormalities in glycogenolysis. For example, glycogen storage disease type V (McArdle disease) results in a lack of glycogen phosphorylase, which impairs glycogen breakdown and prevents muscles from meeting the energy demands of exercise. Glycogen storage disease type III (Cori, or Forbes, disease) is caused by mutations in a gene involved in the production of glycogen debranching enzyme. The disease results in cellular accumulation of abnormal, incompletely broken down glycogen molecules, leading to tissue damage, particularly in the liver and muscles.