Glycogenolysis

Glycogenolysis (also known as "Glycogenlysis") is the conversion of glycogen polymers to glucose monomers. Glycogen is catabolized by removal of a glucose monomer through cleavage with inorganic phosphate to produce glucose-1-phosphate. This derivative of glucose is then converted to glucose-6-phosphate, an intermediate in glycolysis.

The hormones glucagon and epinephrine stimulate glycogenolysis.

Function
Glycogenolysis takes place in the muscle and liver tissues, where glycogen is stored, as a hormonal response to epinephrine (e.g., adrenergic stimulation) and/or glucagon, a pancreatic peptide triggered by low blood glucose concentrations, and produced in the alpha cells of the islets of Langerhans.


 * Liver (hepatic) cells can consume the glucose-6-phosphate in glycolysis or remove the phosphate group using the enzyme glucose-6-phosphatase and release the free glucose into the bloodstream for uptake by other cells.


 * Muscle cells in humans do not possess glucose-6-phosphatase and, hence, will not release glucose, but instead use the glucose-6-phosphate in glycolysis.

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

First step
The overall reaction for the 1st step is:

Glycogen (n residues) + Pi <-> Glycogen (n-1 residues)+ G1P

Here, glycogen phosphorylase cleaves the bond at the 1 position by substitution of a phosphoryl group. It breaks down glucose polymer at &alpha;-1-4 linkages until 4 linked glucoses are left on the branch. (Glycogen phosphorylase (EC 2.4.1.1) can be used as a marker enzyme to determine glycogen breakdown. )

Second step
The second step involves the enzyme [α[1→4]→α[1→4] glucan transferase]/debranching enzyme, which transfers the three remaining glucose units to another 1,4 terminal of glycogen, which exposes the α[1→6] branching point. The final action of this enzyme is the hydrolysis of the remaining glucose attached at the α[1→6] branch point, which gives one free glucose molecule. This is the only case in which a glycogen metabolite is not glucose-1-phosphate. These glucan transferase and debranching enzyme activities are from two separate catalytic sites on the same protein.

Third step
The third and last stage converts G1P (glucose-1-phosphate) to G6P (glucose-6-phosphate) through the enzyme phosphoglucomutase.

Regulation
The key regulatory enzyme of the process of glycogenolysis is glycogen phosphorylase:
 * Phosphorylation --> activation
 * Dephosphorylation --> inhibition