glycogensynthesis

Glycogen synthesis, or glycogenesis, is the metabolic process by which glucose molecules are converted into glycogen for storage, primarily in liver and skeletal muscle. The process begins with glucose uptake and phosphorylation to glucose-6-phosphate, isomerization to glucose-1-phosphate, and activation to UDP-glucose by UDP-glucose pyrophosphorylase. A protein primer, glycogenin, initiates the chain, after which glycogen synthase adds glucose units from UDP-glucose to the growing glycogen chain via α-1,4-glycosidic bonds, extending the chain at the non-reducing ends.

As the chain grows, branching enzyme (amylo-1,4-to-1,6-transglucosylase) introduces α-1,6-linked branches, increasing solubility and access points for rapid synthesis or breakdown. The result is a branched glycogen molecule, composed of glucose units stored in cytosolic granules.

Glycogen synthase is the key rate-limiting enzyme, existing in more active (dephosphorylated) and less active (phosphorylated) forms. Regulation integrates hormonal and allosteric signals: insulin promotes glycogen synthesis by activating protein phosphatase 1, which dephosphorylates and activates glycogen synthase; glucagon and epinephrine, via cAMP and PKA, promote glycogen breakdown and inhibit synthesis. Glucose-6-phosphate can allosterically activate glycogen synthase, particularly in liver and muscle, supporting synthesis when glucose availability is high.

Dysfunction in glycogen synthesis can lead to glycogen storage diseases targeting liver (GYS2 deficiency) or muscle (GYS1), among others.