Glycogenolysis serves the organism to provide glucose-1-phosphate and glucose from the carbohydrate storage form glycogen. Glycogen is stored in large amounts, particularly in the liver and skeletal muscle. Among other things, blood glucose levels are also affected by glycogen metabolism in the liver.
What is glycogenolysis?
Glycogen is present in all cells and is thus directly available for energy supply. However, it is stored in the liver and skeletal muscle to provide energy supply for a certain transitional period, even in the absence of food. Glycogenolysis is characterized by the breakdown of glycogen into glucose-1-phosphate and glucose. About 90 percent glucose-1-phosphate and ten percent glucose are produced. Glycogen is the storage form of glucose, similar to what starch is in plants. It appears as a branched molecule in whose chains the glucose units alpha-1-4 are O-glycosidically linked. At the branching point, in addition to an alpha-1-4 O-glycosidic bond, there is also an alpha-1-6 O-glycosidic bond. Glycogen is not completely degraded. The basic molecule always exists. New glucose molecules are either glycosidically bound to it or split off from it. Only in the form of this tree-like branched molecule is effective energy storage possible. Glycogen is present in all cells and is thus directly available for energy supply. However, it is stored in the liver and in skeletal muscle to ensure energy supply for a certain transitional period, even in the absence of food. When required, it is mainly broken down into the intracellular form glucose-1-phosphate. To regulate blood glucose levels, free glucose is increasingly produced in the liver by enzymatic reactions.
Function and role
Glycogenolysis provides energy to the body in the form of free glucose and the phosphorylated form of glucose. For this purpose, the carbohydrate storage form glycogen is broken down. Since glycogen is found in all body cells, glycogenolysis occurs everywhere. Glycogen is also stored in skeletal muscle and in the liver. In this way, the high energy requirements of skeletal muscles can be met quickly, even in the absence of food. The liver also provides an adequate amount of glucose to regulate blood glucose levels. For this purpose, an additional enzyme, glucose-6-phosphatase, is present in the liver to convert glucose-1-phosphate to glucose-6-phosphate. Glucose-6-phosphate can then be fed to glycolysis, the formation of glucose. The initial steps of glycogenolysis are basically the same in skeletal muscle and liver. The alpha-1-4 O-glycosidic linked glucose molecules in the chains of the tree-like branched molecule glycogen are cleaved by the enzyme glycogen phosphorylase. In this process, the glucose molecule that has been cleaved is linked to a phosphate residue. Glucose-1-phosphate is formed, which can be used immediately for energy production or for transformation into other biomolecules. This cleavage process occurs only up to the fourth glucose unit of the chain before the branch point. To break down the remaining glucose units, the so-called debranching enzyme (4-alpha-glucanotransferase) is now used. This enzyme performs two tasks. First, it catalyzes the separation of three of the four glucose units upstream of the branch point and its transfer to a free non-reducing end of the glycogen. Second, it catalyzes the hydrolysis of the alpha-1-6 branching site, producing free glucose. Because of the ratio of chains to branching sites in glycogen, only ten percent of free glucose is ever produced in this process. However, even larger amounts of free glucose are formed in the liver. As mentioned earlier, the liver has an additional enzyme (glucose-6-phosphatase) that catalyzes the isomerization of the molecule glucose-1-phosphate into glucose-6-phosphate. Glucose-6-phosphate can be easily converted into free glucose. In this way, the liver ensures that blood glucose levels remain constant during food deprivation. When blood glucose levels drop due to physical stress or food deprivation, the hormones glucagon and epinephrine are produced at an increased rate. Both hormones stimulate glycogenolysis and thus ensure a balanced blood glucose level. Glucagon is the antagonist of the hormone insulin, which is increasingly produced when blood glucose levels are high. Insulin inhibits glycogenolysis.
Diseases and ailments
When glycogenolysis is increased, it may be a symptom of a pathological process. For example, the hormone glucagon directly stimulates glycogenolysis by activating a G protein-coupled receptor (GPCR). As a result of the onset of the reaction cascade, a glycogen phosphorylase (PYG) is catalytically activated. Glycogen phosphorylase in turn catalyzes the formation of glucose-1-phosphate from the cleavage of glucose units from glycogen. Thus, with an increased concentration of the hormone glucagon, an increased breakdown of glucogen takes place. The end effect is that larger amounts of glucose are produced, resulting in increased blood glucose levels. Highly elevated concentrations of glucagon occur in the so-called glucagonom. The glucagonom is a neuroendocrine tumor of the pancreas, which permanently produces enormous amounts of glucagon. Thus, the glucagon plasma level can be elevated up to 1000 times the norm. Symptoms of the disease include diabetes mellitus, due to increased glycogenolysis, severely destructive eczema on the face, hands and feet, and anemia. The tumor is usually malignant. Treatment consists in its surgical removal. In case of metastases or inoperability, chemotherapy is performed. Glucogen is also broken down in increased production of adrenaline. Adrenaline is produced in high concentrations in a pheochromocytoma, among others, without the ability to regulate hormone levels. A pheochromocytoma represents hormonally active tumors of the adrenal medulla. The causes of these tumors usually cannot be determined. In the majority of cases, however, they are benign tumors, although they can also degenerate into malignant tumors. In addition to high blood pressure and cardiac arrhythmias, blood glucose levels are greatly elevated due to increased glycogenolysis. Non-specific symptoms are headache, sweating, pallor as well as restlessness, fatigue and leukocytosis. Therapy consists mainly of surgical removal of the tumor.
