Glycogen Metabolism

Structure of Glycogen

Glycogen is a branched chain polysaccharide, made exclusively from alpha D glucose. The primary glycosidic bond is an alpha 1-4 linkage. After an average of eight to ten, glycosyl residues, there is a branch containing an alpha 1-6 linkage.

Non reducing glucosyl residues at the terminal ends are sites of release of glucosyl units. Glycogen is a branched glucose polymer. Branching allows the large number of sites for glucose release. Bonds at branches connect carbon alpha 1-6. Bonds at non branching sites connect alpha carbon 1-4.

 

Functions of Glycogen

The main stores of Glycogen in the body are skeleton muscle and liver.

Muscle Glycogen – to serve as a fuel reserve for the synthesis of ATP during muscle contraction. It releases Glycogen instantly when required

Liver Glycogen – to maintain the blood Glucose concentration, particularly during the early stages of fast. It releases Glycogen over long period of time

 

 

Function of Glycogen stores

Liver Glycogen increases when well fed state and are depleted during fast. Muscle Glycogen not affected by short period of fasting (a few days) and is only moderately decreased in prolonged fasting (weeks). Muscle Glycogen is synthesized to replenish muscle stores after they have been depleted following strenuous exercises.

 

Synthesis of Glycogen (Glycogenesis)

Glycogen is synthesized from molecules of alpha D glucose. The process occurs in the cytosol. Requires energy supplies by ATP (for the phosphorylation of glucose) and uridine triphosphate.

Source of glucosyl residues alpha D glucose attached to Uridine diphosphate. (UDP). UDP glucose is synthesized from glucose-1phosphate and UTP by UDP-Glucose pyro phosphorylase. Glucose – 6Phosphate is converted to Glucose-1phosphate by phosphoglucomutase.  

Glycogen synthase is responsible for making the alpha 1-4 linkages in Glycogen. The enzyme cannot initiate chain synthesis using free glucose as an acceptor of a molecule glucose from UDP – Glucose. It can only elongate already existing chains of  glucose

 

Glycogen primer

1.    Fragment of Glycogen

In cells whose glycogen stores are not totally depleted

2.    In the absence of glycogen fragment, glycogenic (a protein) can serve as an acceptor of glucose residues from UDP- glucose

The side chain of OH group of a specific tyrosine serves as the site at which the initial glucosyl unit Is attached

The reaction catalyzes by Glycogenin itself via autoglucosylation (glycogenin is an enzyme). Glycogenin further catalyzes the transfer of next few molecules of glucose from UDP – Glucose, producing a short alpha 1-4 linked glucosyl chain. This serves as a primer that is able to be elongated by glycogen synthase.

 

 

 

 

 

Formation of branches of Glycogen

Branches located on average eight glucosyl residues apart, resulting highly branched structure.

Branching,

            Increases solubility

            Increasing number of non-reducing ends to which new glucosyl residues can be added (and also which these residues can be removed)

Branches are made by the action of the branching enzyme. It removes a chain of six to eight glucosyl residues. From the nonreducing end of the glycogen chain, breaking an alpha 1-4 bond and attaches it to another terminal glucosyl residue on the chain by an alpha 1-6 linkage. Branching enzyme functioning as a 4:6 transferase. The resulting new non reducing end as well as the old non reducing end from which the six to eight residues were removed can now be further elongated by glycogen synthase