Glycogen synthesis in the liver and muscle

Glycogen synthesis, which occurs through a different metabolic pathway than its breakdown, restores its reserves in the liver and muscle when dietary carbohydrates are available.
In the liver it occurs in the fed state and it is stimulated both by increased glucose availability and insulin.
In post-exercise muscle, glycogen synthesis is faster when there are high blood glucose levels and insulin is available; the hormone stimulates glucose transport into muscle cells, thanks to the mobilization of specific transporters called GLT4, and glycogen synthesis activity.
Glycogen synthesis requires more energy than that recovered during its breakdown: two ATP molecules are spent versus only one ATP molecules saved thanks to glucose-1-phoshate production. Therefore, the energy cost that the cell pays to store glucose as glycogen is an high-energy phosphate bond for each glucose unit.

The steps in glycogen synthesis

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

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

The next step is UDP-glucose production from glucose-1-phosphate and UTP in the reaction catalyzed by UDP-glucose pyrophosphorylase; the reaction, reversible (and the name of the enzyme is due to the reverse reaction), becomes irreversible thanks 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

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

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.
The overall balanced equation for glycogen synthesis is:

glycogen(n glucose residues) + glucose + 2 ATP → glycogen(n+1 glucose residues) + 2 ADP + 2 Pi

Glycogen Synthesis: Glycogen Branching Enzyme
Fig. 1 – Glycogen Branching Enzyme

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.
Then, glycogen synthase may add further glucose residues to the new branch.

References

Berg J.M., Tymoczko J.L., and Stryer L. Biochemistry. 5th edition.  W. H. Freeman and Company, 2002

Nelson D.L., M. M. Cox M.M. Lehninger. Principles of biochemistry. 4th Ed. W.H. Freeman and Company, 2004

Rawn J.D. Biochimica. Mc Graw-Hill, Neil Patterson Publishers, 1990

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