Glycogenesis: How to Synthesize Glycogen
“Synthesis of Glycogen from Glucose is called GLYCOGENESIS. It takes place in the Cytosol and requires ATP and UTP, besides Glucose.” The goal of glycolysis, glycogenolysis, and the citric acid cycle is to conserve energy as ATP from the catabolism of carbohydrates. If the cells have sufficient supplies of ATP, then these pathways and cycles are inhibited. Under these conditions of excess ATP, the liver will attempt to convert a variety of excess molecules into glucose and/or glycogen.
Steps involved in Glycogenesis:
There are 6 major steps are involved in the Glycogenolysis:
Step 1: Glucose Phosphorylation:
Glucose is phosphorylated into Glucose-6-Phosphate, a reaction that is common to the first reaction in the pathway of glycolysis from Glucose. This reaction is catalyzed by Hexokinase in Muscle and Glucokinase in Liver.
Glucose + ATP –> Glucose-6-P
(Enzyme: Glucokinase or Hexokinase)
Step 2: Glc-6-P to Glc-1-P conversion:
Glucose-6-P is converted to Glc-1-Phosphate in a reaction catalyzed by the enzyme “Phosphoglucomutase”.
Glucose-6-P + Enz-P <—> Glucose-1,6-bis Phosphate + Enz
<—> Glucose-1-Phosphate + Enzyme-P
Step 3: Attachment of UTP to Glc-1-P:
Glucose-1-P reacts with Uridine triphosphate (UTP) to form the active nucleotide Uridine diphosphate Glucose (UDP-Glc). The reaction is catalyzed by the enzyme “UDPGlc Pyrophosphorylase”.
UTP + Glucose-1-P <—> UDPGlc + PPi
(Enzyme: UDPGlc Pyrophosphorylase)
Step 4: Attachment of UDP-Glc to Glycogen Primer:
A small fragment of pre-existing glycogen must act as a “Primer” (also called GLYCOGENIN) to initiate glycogen synthesis. The Glycogenin can accept glucose from UDP-Glc.
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 it self takes up a for glucose residues to form a fragment of primer which serves as an acceptor for the rest of the glucose molecules.
Step 5: Glycogen synthesis by Glycogen synthase:
Glycogen synthase, the enzyme transfers the Glucose from UDP-Glc to the non-reducing end of Glycogen to form alpha 1,4-linkages. Glycogen synthase catalyze the synthesis of a linear unbranched molecule with alpha-1,4-glycosidic linkages.
Step 6: Glycogen Branches formation:
In this step, the formation of branches is brought about by the action of a branching enzyme, namely branching enzyme (amylo-[1—>4]—>[1—>6]-transglucosidase).
This enzyme transfers a small fragment of five to eight glucose residues from the non-reducing end of glycogen chain. to another glucose residue where it is linked by alpha-1,6 bond.
It leads to the formation of a new non-reducing end, besides the existing one. Glycogen chain wil be elongated and branched.
Overall reaction of Glycogenesis,
(Glucose)n + Glucose + 2 ATP –> (Glucose) n+1 + 2 ADP + Pi
Two ATP molecules will utilize in this process. One is required for the phosphorylation of Glucose and other is needed for conversion of UDP to UTP.