Structural Biochemistry/Carbohydrates/Glycogen Breakdown

Overview
Glucose is a monosaccharide that fuels cells. Since a high concentration of glucose destroys the osmotic state of the cell, resulting in cell damage, hence glucose is not used for energy storage. Instead glycogen, a form of glucose that serves the purpose of energy storage, is used. Glycogen is a multibranched polysaccharide that can be broken down into glucose and used as a source of energy.

4 enzyme activities are needed for the breakdown of glycogen in providing 6-phosphate:
 * 1) Degradation of glycogen
 * 2) Remodeling of glycogen
 * 3) Remodeled glycogen as a substrate
 * 4) Conversion of product

Degradation of glycogen: Production of glucose 1-phosphate
Glycogen phosphorylase is the major enzyme in helping with the breakdown of glycogen. Through the addition of orthophosphate, denoted Pi, glycogen phosphorylase cleaves the substrate to form glucose 1-phosphate. Phosphorylase sequentially removes the residues from the nonreducing side the glycogen by having the Pi to cleave the glycosidic linkage between C1 carbon and the oxygen. As a result, glucose 1-phosphate from the cleavage along with the enzyme phosphoglucomutase converts to glucose 6-phosphate.



Remodeling of glycogen: Participation of pyridoxal phosphate

 * 1) A proton from Pi is transferred to the oxygen on C4 of the glycogen chain and at the same time Pi grabs a proton from the pyridoxal phosphate (PLP).


 * 1) An intermediate, carbonium ion, is formed


 * 1) Pi attacks the carbonium ion, leading to the formation of α-glucose 1-phosphate along with the addition of a proton back to the PLP

Remodeled glycogen as substrate: Aid from a debranching enzyme
Cleavage of α-1, 4 bond stops when phosphorylase reaches the fourth residue away from the development of branch. Two more enzymes, transferase and α-1, 6-glucosidase, are introduced to further facilitate the remodeling of glycogen. The transferase moves three residues from one branch to another. Then α-1,6 glycosidic bond is hydrolyzed by α-1,6 glucosidase, releasing a glucose. In general, the goal of transferase and α-1,6 glucosidase is to turn the branched molecule to into linear form.



Conversion of product: Production of glucose 6-phosphate
The enzyme phosphoglucomutase has a phosphorylated serine residue at its active site, and the phosphoryl group is later added to glucose 1-phosphate, more specifically, at C6 hydroxyl group, to yield glucose 1, 6-bisphosphate. At the same time, the C1 phosphoryl group of the substrate is added to the serine residue of phosphoglucomutase, ending up with glucose 6-phosphate and phosphoenzyme.

Reference
Berg, Jeremy "Biochemistry", Chapter 21 Glycogen Metabolism. 615-620. Seventh edition. Freeman and Company, 2010.