GLYCOGENESIS

GLYCOGENESIS

The synthesis of glycogen from glucose is glycogenesis . Glycogenesis takes place in the cytosol and requires ATP and UTP, besides glucose.

1. Synthesis of UDP-glucose : The enzymes hexokinase (in muscle) and glucokinase (in liver) convert glucose to glucose 6-phosphate. Phosphoglucomutase catalyses the conversion of glucose 6-phosphate to glucose 1-phosphate. Uridine diphosphate glucose (UDPG) is synthesized from glucose 1-phosphate and UTP by UDP-glucose pyrophosphorylase.

2. Requirement of primer to initiate glycogenesis : A small fragment of pre-existing glycogen must act as a ‘primer’ to initiate glycogen synthesis. It is recently found that in the absence of glycogen primer, a specific protein—namely ‘glycogenin’—can accept glucose from UDPG. The hydroxyl group of the amino acid tyrosine of glycogenin is the site at which the initial glucose unit is attached. The enzyme glycogen initiator synthase transfers the first molecule of glucose to glycogenin. Then glycogenin itself takes up a few glucose residues to form a fragment of primer which serves as an acceptor for the rest of the glucose molecules.

3. Glycogen synthesis by glycogen synthase : Glycogen synthase is responsible for the formation of 1,4-glycosidic linkages. This enzyme transfers the glucose from UDP-glucose to the non-reducing end of glycogen to form - 1,4 linkages.

4. Formation of branches in glycogen : Glycogen synthase can catalyse the synthesis of a linear unbranched molecule with 1,4 - glycosidic linkages. Glycogen, however, is a branched tree-like structure. The formation of branches is brought about by the action of a branching enzyme, namely glucosyl -4-6 transferase. (amylo 1,4 1,6 trans- glucosidase). This enzyme transfers a small fragment of five to eight glucose residues from the non-reducing end of glycogen chain (by breaking -1,4 linkages) to another glucose residue where it is linked by -1,6 bond. This leads to the formation of a new non-reducing end, besides the existing one. Glycogen is further elongated and branched, respectively, by the enzymes glycogen synthase and glucosyl 4-6 transferase.

The overall reaction of the glycogen synthesis for the addition of each glucose residue is

(Glucose)n + Glucose + 2ATP (Glucose)n+1 + 2 ADP + Pi

Of the two ATP utilized, one is required for the phosphorylation of glucose while the other is needed for conversion of UDP to UTP.

   GLYCOGEN SYNTHESIS 

GLYCOGENESIS

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