Glycogenolysis is the breakdown of glycogen (n) to

glucose-1-phosphate Glucose 1-phosphate (also called cori ester) is a glucose molecule with a phosphate group on the 1'-carbon. It can exist in either the α- or β- anomeric form. Reactions of α-glucose 1-phosphate Catabolic In glycogenolysis, it is the direct p ...

and glycogen (n-1). Glycogen branches are

catabolized Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipids, ...

by the sequential removal of glucose monomers via

phosphorolysis Phosphorolysis is the cleavage of a compound in which inorganic phosphate is the attacking group. It is analogous to hydrolysis.Stryer, L. (1988) Biochemistry, 3rd ed., Freeman (p. 451) An example of this is glycogen breakdown by glycogen phospho ...

, by the enzyme

glycogen phosphorylase Glycogen phosphorylase is one of the phosphorylase enzymes (). Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond. Glycogen phosphory ...

Mechanism

The overall reaction for the breakdown of glycogen to glucose-1-phosphate is: : glycogen_{(n residues)} + P_i glycogen_{(n-1 residues)} + glucose-1-phosphate Here,

cleaves the bond linking a terminal glucose

residue Residue may refer to: Chemistry and biology * An amino acid, within a peptide chain * Crop residue, materials left after agricultural processes * Pesticide residue, refers to the pesticides that may remain on or in food after they are applied ...

to a glycogen branch by substitution of a

phosphoryl {{unreferenced, date=May 2015 A phosphoryl group is the chemical ion or radical: P+O32−, containing phosphorus and oxygen. (The correct chemical name for this −PO32− group is phosphonato, and phosphono for −PO3H2; as ''phosphoryl'' in ch ...

group for the α →4linkage. Glucose-1-phosphate is converted to

glucose-6-phosphate Glucose 6-phosphate (G6P, sometimes called the Robison ester) is a glucose sugar phosphorylated at the hydroxy group on carbon 6. This dianion is very common in cells as the majority of glucose entering a cell will become phosphorylated in this wa ...

(which often ends up in

glycolysis Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...

) by the enzyme

phosphoglucomutase Phosphoglucomutase () is an enzyme that transfers a phosphate group on an α-D-glucose monomer from the 1 to the 6 position in the forward direction or the 6 to the 1 position in the reverse direction. More precisely, it facilitates the interconve ...

. Glucose residues are phosphorolysed from branches of glycogen until four residues before a glucose that is branched with a α →6linkage.

Glycogen debranching enzyme A debranching enzyme is a molecule that helps facilitate the breakdown of glycogen, which serves as a store of glucose in the body, through glucosyltransferase and glucosidase activity. Together with phosphorylases, debranching enzymes mobiliz ...

then transfers three of the remaining four glucose units to the end of another glycogen branch. This exposes the α →6branching point, which is

hydrolysed Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis ...

by α →6glucosidase, removing the final glucose residue of the branch as a molecule of glucose and eliminating the branch. This is the only case in which a glycogen metabolite is not glucose-1-phosphate. The glucose is subsequently phosphorylated to glucose-6-phosphate by

hexokinase A hexokinase is an enzyme that phosphorylates hexoses (six-carbon sugars), forming hexose phosphate. In most organisms, glucose is the most important substrate for hexokinases, and glucose-6-phosphate is the most important product. Hexokina ...

Function

Glycogenolysis takes place in the cells of the

muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

and

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

tissues in response to hormonal and neural signals. In particular, glycogenolysis plays an important role in the

fight-or-flight response The fight-or-flight or the fight-flight-or-freeze response (also called hyperarousal or the acute stress response) is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first des ...

and the regulation of glucose levels in the blood. In

myocyte A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscl ...

s (muscle cells), glycogen degradation serves to provide an immediate source of glucose-6-phosphate for

, to provide energy for muscle contraction. In

hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...

s (liver cells), the main purpose of the breakdown of glycogen is for the release of glucose into the bloodstream for uptake by other cells. The phosphate group of glucose-6-phosphate is removed by the enzyme

glucose-6-phosphatase The enzyme glucose 6-phosphatase (EC 3.1.3.9, G6Pase; systematic name D-glucose-6-phosphate phosphohydrolase) catalyzes the hydrolysis of glucose 6-phosphate, resulting in the creation of a phosphate group and free glucose: : D-glucose 6-phos ...

, which is not present in myocytes, and the free glucose exits the cell via

GLUT2 Glucose transporter 2 (GLUT2) also known as solute carrier family 2 (facilitated glucose transporter), member 2 (SLC2A2) is a transmembrane carrier protein that enables protein facilitated glucose movement across cell membranes. It is the principa ...

facilitated diffusion channels in the hepatocyte cell membrane.

Regulation

Glycogenolysis is regulated hormonally in response to blood sugar levels by

glucagon Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...

and

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

, and stimulated by

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...

during the

. Insulin potently inhibits glycogenolysis. In myocytes, glycogen degradation may also be stimulated by neural signals.

Clinical significance

Parenteral (

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

) administration of

is a common human medical intervention in

diabetic Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased app ...

emergencies when sugar cannot be given orally. It can also be administered

intramuscularly Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...

Pathology

References

External links

The chemical logic of glycogen degradation at ufp.pt
* {{Glycogenesis and glycogenolysis Metabolic pathways Hepatology Diabetes