glycogenesis

Glycogenesis is the biosynthesis of glycogen, the branched polymer of glucose, from glucose units. In humans, it occurs primarily in liver and skeletal muscle, serving to store excess glucose for later use. Liver glycogen helps maintain blood glucose during fasting; muscle glycogen supplies glucose for muscle contraction during activity but is not released into the bloodstream.

The process begins with uptake and phosphorylation of glucose by hexokinase in muscle or glucokinase in liver, producing glucose-6-phosphate. Through phosphoglucomutase, glucose-6-phosphate is converted to glucose-1-phosphate, which is activated by UDP-glucose via UDP-glucose pyrophosphorylase to form UDP-glucose. Glycogen synthase then adds glucose from UDP-glucose to the growing chain by forming α-1,4 glycosidic bonds. A primer provided by glycogenin initiates the chain. After several units, branching enzyme creates α-1,6 bonds to form branches, increasing solubility and rapid mobilization.

Regulation: Glycogen synthase is the key rate-limiting enzyme of glycogenesis. It is activated by dephosphorylation (mediated by protein phosphatase-1 under insulin signaling) and allosterically activated by glucose-6-phosphate. It is inhibited when phosphorylated by hormones such as glucagon and epinephrine via cAMP-dependent protein kinase A, especially in the liver. In contrast, muscle glycogenesis is more sensitive to insulin and energy status; muscle lacks glucose-6-phosphatase, so stored glycogen cannot contribute to blood glucose.

Clinical notes: Disorders of glycogen synthesis are rare but can involve defects in glycogenin, glycogen synthase, or branching enzyme, affecting glycogen structure and storage. Understanding glycogenesis is fundamental to carbohydrate metabolism and energy homeostasis.