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Glycogen phosphorylase is one of the phosphorylase enzymes (EC 2.4.1.1). It breaks up glycogen into glucose subunits. Glycogen is left with one less glucose molecule, and the free glucose molecule is in the form of glucose-1-phosphate. In order to be used for metabolism, it must be converted to glucose-6-phosphate by the enzyme phosphoglucomutase.

Glycogen phosphorylase can only act on linear chains of glycogen (α1-4 glycosidic linkage). Its work will immediately come to a halt four residues away from α1-6 branch (which are exceedingly common in glycogen). In these situations, a debranching enzyme is necessary, which will straighten out the chain in that area. Additionally, an α1-6 glucosidase enzyme is required to break the remaining α1-6 residue that remains in the new linear chain. After all this is done, glycogen phosphorylase can continue.

Glycogen phosphorylase has a pyridoxal phosphate (PLP derived from Vitamin B₆) at each catalytic site. Pyridoxal phosphate links with basic residues and covalently forms a Schiff base which helps attack the substrate. PLP is covalently linked to the protein via the ε-amino group of a lysyl residue. PLP therefore stabilizes the attacking phosphate group.

Regulation

Glycogen phosphorylase is regulated by both allosteric control and by phosphorylation (covalent modification).

Hormones such as epinephrine and glucagon regulate glycogen phosphorylase using second messenger amplification systems that are linked to G proteins. Epinephrine activates adenylate cyclase through a G-protein that in turn increases levels of cAMP. cAMP binds to and releases an active form of protein kinase A (PKA). Next, PKA phosphorylates phosphorylase kinase which in turn phosphorylates glycogen phosphorylase b, transforming it into the active glycogen phosphorylase a. This phosphorylation is added onto the glycogen phosphorylase a seryl 14. In the liver, epinephrine activates another G-protein linked receptor that triggers a different cascade resulting in the activation of Phospholipase C (PLC). PLC indirectly causes the release of calcium from the hepatocytes endoplasmic reticulum into the cytosol. The increased calcium availability binds to calmodulin and activates PKA. PKA activates glycogen phosphorylase in the same manner mentioned previously.

Glycogen phosphorylase b is not always inactive in muscle, as it can be activated allosterically by AMP. An increase in AMP concentration, which occurs during strenuous exercise, signals energy demand. AMP activates glycogen phosphorylase b by changing its conformation from a tensed to a relaxed form. This relaxed form has similar enzymatic properties as the phosphorylated enzyme. An increase in ATP concentration opposes this activation by displacing AMP, indicating sufficient energy stores.

Upon eating a meal there is a release of insulin, signaling glucose availability in the blood. Insulin indirectly activates PP-1 and phosphodiesterase. The PP-1 directly dephosphorylates glycogen phosphorylase a reforming the inactive glycogen phosphorylase b. The phosphodiesterase converts cAMP to AMP. This activity removes the second messenger (generated by glucagon and epinephrine) and inhibits PKA. In this manner, PKA can no longer cause the phosphorylation cascade that ends with formation of (active) glycogen phosphorylase a. These modifications initiated by insulin end glycogenolysis in order to preserve what glycogen stores are left in the cell and trigger glyconeogenesis (rebuilding of glycogen).

See also

• McArdle's Disease (deficiency of (muscle) myophosphorylase)
• Hers' Disease (deficiency of liver phosphorylase)

External links

• The Glycogen Phosphorylase Protein
• MeSH Glycogen+phosphorylase

Wikipedia content modification information:

• This page was last modified on 31 May 2008, at 12:28.

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