Glycogenolysis is the breakdown of glycogen (n) to glucose-1-phosphate and glycogen (n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase.

Mechanism

In the muscles, glycogenolysis begins due to the binding of cAMP to phosphorylate kinase, converting the latter to its active form so it can convert phosphorylase b to phosphorylase a, which is responsible for catalyzing the breakdown of glycogen. 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, glycogen phosphorylase cleaves the bond linking a terminal glucose residue to a glycogen branch by substitution of a phosphoryl group for the α →4linkage. Glucose-1-phosphate is converted to glucose-6-phosphate (which often ends up in glycolysis) by the enzyme phosphoglucomutase. Glucose residues are phosphorolysed from branches of glycogen until four residues before a glucose that is branched with a α →6linkage. Glycogen debranching enzyme 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 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.

Enzymes

# Glycogen phosphorylase with Pyridoxal phosphate as prosthetic group # Alpha-1,4 → alpha-1,4 glucan transferase # Alpha-1,6-glucosidase # Phosphoglucomutase # Glucose-6-phosphatase (absent in muscles)

Function

Glycogenolysis takes place in the cells of the

muscle Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...

and

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

tissues in response to hormonal and neural signals. In particular, glycogenolysis plays an important role in the fight-or-flight response and the regulation of glucose levels in the blood. In

myocyte A muscle cell, also known as a myocyte, is a mature contractile Cell (biology), cell in the muscle of an animal. In humans and other vertebrates there are three types: skeletal muscle, skeletal, smooth muscle, smooth, and Cardiac muscle, cardiac ...

s (muscle cells), glycogen degradation serves to provide an immediate source of glucose-6-phosphate for glycolysis, to provide energy for muscle contraction. Glucose-6-phosphate can not pass through the cell membrane, and is therefore used solely by the myocytes that produce it. In hepatocytes (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, which is not present in myocytes, and the free glucose exits the cell via GLUT2 facilitated diffusion channels in the hepatocyte cell membrane.

Regulation

Glycogenolysis is regulated hormonally in response to blood sugar levels by glucagon and

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

, and stimulated by epinephrine during the fight-or-flight response. Insulin potently inhibits glycogenolysis. In myocytes, glycogen degradation may also be stimulated by neural signals; glycogenolysis is regulated by epinephrine and calcium released by the sarcoplasmic reticulum. Glucagon has no effect on muscle glycogenolysis. Calcium binds with calmodulin and the complex activates phosphorylase kinase.

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 nutr ...

) administration of glucagon is a common human medical intervention in diabetic emergencies when sugar cannot be given orally. It can also be administered intramuscularly.

Pathology

References

External links

The chemical logic of glycogen degradation at ufp.pt
* {{Authority control Biochemical reactions Carbohydrate metabolism Diabetes Hepatology