GLYCOGEN METABOLISM

Glycogen is a branched homopolysaccharides made exclusively from a-D-glucose. Glycogen is the storage form of carbohydrates in the human body. The major sites of storage are liver and muscle. The major function of liver glycogen is to provide glucose during fasting, when blood glucose level falls, liver glycogen is broken down and helps to maintain blood glucose level. After taking food, blood glucose tends to rise, which causes glycogen deposition in liver. About 5 hours after taking food, the blood glucose tends to fall, but, glycogen is lysed to glucose so that the energy needs are met. After about 18 hours fasting, most of the liver glycogen is depleted, at this time depot fats are hydrolysed and energy requirement is met by fatty acid oxidation.
The function of muscle glycogen is to act as reserve fuel for muscle contraction.

GLYCOGEN SYNTHESIS (GLYCOGENESIS)
The glycogen synthesis occurs by a pathway distinctly different from the reversal of glycogenolysis. The steps are:

1. Activation of Glucose
UDP glucose is formed from glucose-1-phosphate and UTP (uridine triphosphate) by the enzyme glucose-1-uridyltransferase.

2. Glycogen Synthase
The glucose moiety from UDP-glucose is transferred to glycogenin (a glycogen primer molecule which is essential to accept the glycosyl unit), The primer is made up of a protein-carbohydrate complex.

Glycogen synthase
Glycogen primer (n) + UDP glucose ————? Glycogen (n+1) + UDP


In this step, activated glucose units are sequentially added by the enzyme glycogen synthase .The glucose unit is added to the non-reducing (outer) end of the glycogen primer to form an alpha-1,4 glycosidic linkage and UDP is liberated.

3. Branching Enzyme
The glycogen synthase can add glucose units only in alpha-1,4 linkage. A branching enzyme is needed to create the alpha-1,6 linkages. When the chain is lengthened to 11 – 12 glucose residues, the branching enzyme will transfer a block of 6 to 8 glucose residues from this chain to another site on the growing molecule. The enzyme amylo-[1,4]?[1,6]-transglucosidase (branching enzyme) forms this alpha-1,6 linkage . To this newly created branch, further glucose units can be added in alpha-1,4 linkage by glycogen synthase.

DEGRADATION OF GLYCOGEN (GLYCOGENOLYSIS)
1. Glycogen Phosphorylase
Glycogen phosphorylase removes glucose as glucose-1-phosphate from glycogen. It removes glucose units one at a time. Enzyme sequentially hydrolyses alpha-1,4 glycosidic linkages, till it reaches a glucose residue, 3-4 glucose units away from a branch point. It cannot attack the 1,6 linkage at branch point. If glycogen phosphorylase alone acts on a glycogen molecule, the final product is a highly branched molecule; it is called limit dextrin. PLP (pyridoxal phosphate)



2. Debranching by bifunctional two Enzymes
Then a block of 3 glucose residues (trisaccharide unit) are transferred from the branching point to another branch by enzyme alpha-1,4 ? alpha-1,4 glucan transferase. Now the branch point is free. Then alpha-
1,6- glucosidase (debranching enzyme) can hydrolyse the remaining glucosyl unit held in alpha-1,6 linkage at the branch point. This glucose residue is released as free glucose. At this stage, the ratio of glucose-1-
phosphate to free glucose is about 8:1.The transferase and alpha-1,6-glucosidase will together convert the branch point to a linear one. With the removal of the branch point, phosphorylase enzyme can proceed with its action.