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Glycogen Metabolism


Glycogen is a large branched polymer of glucose molecules linked by â-1,4 glycosidic linkages, branches arise by α-1,6 glycosidic linkage at approximately every fifth to tenth residue.

Glycogen is storage form of carbohydrate in animals.  It occurs mainly in liver (6%), muscle it rarely exceeds 1%, but because of greater muscle mass, muscle represent 3-4 times as much glycogen store as liver.

The general structure of glycogen is shown below :



Fig: The glycogen molecule. A. General structure. B. Enlargement of structure at a branch point. The molecule is a sphere approximately 21 nm in diameter that can be seen in electron micrographs. It has a molecular mass of 107 Da and consists of polysaccharide chains, each containing about 13 glucose residues. The chains are either branched or unbranched and are arranged in 12 concentric layers (only four are shown in the figure). The branched chains (each has two branches) are found in the inner layers and the unbranched chains in the outer layer. (G, glycogenin, the primer molecule for glycogen synthesis.)  

  1. Glycogenesis : (Glycogen Synthesis)
    1. Glucose is phosphorylated to glucose-6-phosphate and then converted to glucose-1-phosphate (G1P)
    2. G1P reacts with uridine triphosphate to form the active nucleotide diphosphate glucose (UDPG). 
    3. Glycogen synthase enzyme catalyses the transfer of glucose units of UDGP to pre-existing glycogen chain or glycogen primer. Glycogen primer is made by glycogenin, a 37 Kda protein on which first glucose molecule is transferred to synthesize new or fresh glycogen molecule.
    4. A branching enzyme transfers a part of α-1, 4 chain to a neighboring chain to form α1:6 linkage, thus establishing the branching points in the molecule. 
  2. Glycogenolysis (glycogen breakdown)
    1. Phosphorylase enzyme specifically acts on the terminal α-1,4 glycosidic bonds of glycogen molecules resulting in liberation of glucose units until four glucose residue remain on each side of branch point.
    2. A specific glucan transferase will then transfer a trisaccharide unit from one side to the other, thus exposing the branch point.
    3. A debranching enzyme will act on α-1,6 linkage to liberate a free glucose residue.


Fig: Pathways of glycogenesis and of glycogenolysis in the liver. (+), Stimulation; (-), inhibition. Insulin decreases the level of cAMP only after it has been raised by glucagon or epinephrine; i.e., it antagonizes their action. Glucagon is active in heart muscle but not in skeletal muscle. At*: Glucan transferase and debranching enzyme appear to be two separate activities of the same enzyme.

  1. Regulatory enzymes:
    1. Phosphorylase enzyme is the rate limiting enzyme in the process of glycogenolysis.
    2. Glycogenolysis in liver produces glucose as an end-product but in muscle there is no glucose 6-phosphatase enzyme so end-product of glycogenolysis is glucose-6-phosphate. Therefore free glucose is not formed in muscle and therefore glucose from muscle doesn’t come out of muscle to raise blood glucose level.

Allosteric control of phosphorylase occurs through

In muscle

In liver





Ca++ (Through δ subunit of phosphorylase kinase)


5’ AMP


 Glucose 6 phosphate




 Glucose 6 phosphate

 Free glucoseQ

  1. Difference between Liver & Muscle Phosphorylase
    1. In the liver the role of glycogen is to provide free glucose for export to maintain the blood concentration of glucose; in muscle the role of glycogen is to provide a source of glucose 6-phosphate for glycolysis in response to the need for ATP for muscle contraction.
    2. In both tissues, the enzyme is activated by phosphorylation catalyzed by phosphorylase kinase (to yield phosphorylase a) and inactivated by dephosphorylation catalyzed by phosphoprotein phosphatase (to yield phosphorylase b), in response to hormonal and other signals.
    3. Active phosphorylase a in both tissues is allosterically inhibited by ATP and glucose 6-phosphate; in liver, but not muscle, free glucose is also an inhibitor.
    4. Muscle phosphorylase differs from the liver isoenzyme in having a binding site for 5'AMP, which acts as an allosteric activator of the (inactive) dephosphorylated b-form of the enzyme.
    5. 5'AMP acts as a potent signal of the energy state of the muscle cell; it is formed as the concentration of ADP begins to increase (indicating the need for increased substrate metabolism to permit ATP formation), as a result of the reaction of adenylate kinase: 2 x ADP ↔ ATP + 5'AMP
    6. The role of glycogen in liver is to provide free glucose for export to maintain the blood glucose level; whereas in muscles the role of glycogen is to provide a source of glucose-6 PO4 for glycolysis (to supply ATP for muscle contraction).
    7. This difference of fate of glycogen in liver & muscle is d/t absence of glucose-6 phosphatase enzyme in muscle. Because of absence of this enzyme, which catalyzes the final step of glycogenolysis, glycogen in muscles can only be converted upto glucose-6 phosphate.
    8. Hence muscle glycogenolysis does not contribute to blood glucose directly.


  1. Glycogen Storage diseases are caused by genetic defects that results in deficiency in certain enzymes of glycogen metabolism.
  2. The causes and characteristic of several glycogen storage diseases are listed in table below:  



Deficient Enzyme


Type 1

Von Gierke’s disease


Hypoglycemia lacticacidemia, ketosis, hyperlipemia

Type II

Pompe’s disease

lysosomal α-1,4 and α-1,6 glucosidase (ACID MALTASE)

Fatal, accumulation of glycogen in lysosomes, heart failure.

Type III

Cori’s disease or Limit dextrinosis or Forbe’s

debranching enzyme

Accumulation of characteristic branched polysaccharide.

Type IV

Andersen’s disease

branching enzyme

Death due to cardiac or liver failure in first year of life.

Type V

McArdle’s syndrome

muscle phosphorylase

Diminished exercise tolerance; muscles have abnormally high glycogen content

Type VI

Her’s disease

liver phosphorylase

High glycogen content in liver, tendency towards hypoglycemia.

Type VII

Tarui’s disease

Muscle phosphofructokinase

As in type V.


Hepatic phosphorylase kinase deficiency

liver phosphorylase kinase

As in Type VI.

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