Glycogenogenesis

Glycogenogenesis is the metabolic pathway that results in the formation of glycogen from glucose. It is a key process in regulating blood glucose levels, particularly when glucose is abundant. This process primarily occurs in the liver and muscles, with the liver's glycogen stores serving a systemic role in maintaining blood glucose homeostasis, while muscle glycogen is reserved for the energy needs of the muscle itself.

The synthesis of glycogen begins with glucose entering the cell. Glucose is then phosphorylated to glucose-6-phosphate. This step is catalyzed by hexokinase in most tissues and glucokinase in the liver. Glucose-6-phosphate is then isomerized to glucose-1-phosphate. This conversion is catalyzed by phosphoglucomutase. Subsequently, glucose-1-phosphate is activated by reacting with uridine triphosphate (UTP) to form uridine diphosphate glucose (UDP-glucose). This reaction is catalyzed by UDP-glucose pyrophosphorylase, releasing pyrophosphate which is rapidly hydrolyzed to drive the reaction forward.

The final step involves UDP-glucose being added to a growing glycogen chain. Glycogen synthase is the enzyme responsible for this elongation. It transfers the glucose unit from UDP-glucose to the non-reducing end of an existing glycogen primer molecule, forming an alpha-1,4 glycosidic bond. Since glycogen synthase can only add glucose to pre-existing chains, a primer molecule of glycogen is required to initiate the process. This primer is typically a small protein called glycogenin, which autoglycosylates itself with a few glucose residues. Once a primer is established, glycogen synthase can extend the chain. Branching of the glycogen molecule is also important for solubility and access to more terminal glucose units for rapid release. This branching, creating alpha-1,6 glycosidic bonds, is accomplished by the enzyme branching enzyme (amylo-1,4-1,6-transglycosylase).