Glycogen Synthesis

1.The first step in glycogen synthesis is glucose activation to glucose-6-phosphate, in the reaction catalyzed by glucokinase in the liver and hexokinase in the muscle and the other organs and tissues. glucose + ATP → glucose-6-phosphate + ADP

2.When glycogen synthesis is occurring phosphoglucomutase , the same enzyme that acts also during glycogenolysis catalyzing the conversion of glucose 1-phosphate to glucose-6-phosphate, shifts the phosphate group from C6 to C1 (therefore the enzyme catalyses a reversible reaction).

glucose-6-phosphate → glucose-1-phosphate

3. The next step is UDP-glucose production from glucose-1-phosphate and UTP in the reaction catalyzed by UDP-glucose pyrophosphorylase ; the reaction becomes irreversible due to the rapid hydrolysis of pyrophosphate to inorganic phosphate in the reaction catalyzed by pyrophosphatase glucose-1-phosphate + UTP → UDP-glucose + PPi

PPi + H2O → 2 Pi 4. Then glycogen synthase transfers the activated glucose to 4’-OH group of a glucose residue (a nonreducing termini) present in the molecule catalyzing the formation of an α-(1,4) glycosidic bond and therefore extending the chain by one glucose unit and releasing the UDP. It should be noted that thus far 2 ATP molecules are consumed per molecule of glucose activated to UDP-glucose: one for glucose-1-phosphate production and the other for the re-synthesis of UPT from UDP in the reaction catalyzed by nucleoside diphosphate kinase .

UDP + ATP → UTP + ADP

5.The overall balanced equation for glycogen synthesis is: glycogen(n glucose residues) + glucose + 2 ATP → glycogen(n+1 glucose residues) + 2 ADP + 2 Pi

6..The branches are inserted in the reaction catalyzed by the branching enzyme, also called amylo-α- (1,4)→α-(1,6)-transglucosidase , that catalyzes the transfer en bloc of an oligosaccharide of six to seven glucose units from a nonreducing termini of a newly elongated chain of at least eleven units to another chain forming a new α-(1,6) glycosidic bond. The new branches are introduced at least at four glucose residues from an adjacent branch point.

Glycogenin (Glycogenin glucosyltransferase, is a transferase (a37kDa protein) responsible for the biosynthesis of glycogen; an important storage form of glucose in the body. It is a unique enzyme in that it is primer, substrate, catalyst, and product of its enzymatic reaction and extension process of glycogen biosynthesis. This is initiated by its ability to transfer glucose from UDP-glucose to form an oligosaccharide of eight glucose units that is covalently attached to itself at Tyr-194 in a multistep reaction mechanism .

After the formation of the nascent chain on the glycogenin molecule the glycogen synthase takes over.

Branching enzyme is a 4to6 glycosyltransferase. Or amylo (1to4) to (1to6) transglycosylase.

Prepared and compiled