Glycogen Metabolism Overview

Glycogen: A polymer of glucose, primarily stored in the liver and muscle tissue. It functions as a medium-term energy storage and a reservoir of glucose. Glycogen levels mobilize when energy or glucose are scarce and are synthesized from glucose when plentiful.

Glycogen Biosynthesis

• Key Intermediate: Glucose-6-phosphate, produced from glucose and ATP, plays a crucial role in glycogen synthesis.

• Isomerization Step: Converts glucose-6-phosphate to glucose-1-phosphate through a rearrangement where the phosphate group is moved from the sixth carbon to the first. This step is crucial as it prepares glucose for activation.

• Activation of Glucose: UDP-glucose is formed from glucose-1-phosphate and UTP. The reaction involves UTP reacting with glucose-1-phosphate, expelling pyrophosphate. This transformation is vital as UDP-glucose is the activated form of glucose used in glycogen synthesis.

• Glycogen Chain Formation: This process occurs through alpha-1,4 glycosidic bonds formation. Carbon 1 of the incoming glucose unit binds to carbon 4 of the terminal glucose in the pre-existing glycogen chain. UDP serves as a leaving group during bond formation, facilitating the synthesis process. Electrophilic glucose oxycation is formed for the bond reaction with the hydroxyl group of glycogen.

• Retention of Configuration: The alpha configuration of glucose is preserved throughout the synthesis, ensuring the functionality of glycogen in metabolic pathways.

Branching in Glycogen

• Glycogen is highly branched, enhancing its solubility and mobilization efficiency. Branch points are created by linking carbon 1 of glucose to carbon 6 of a branch point glucose, forming alpha-1,6 bonds.

• This branching structure allows for multiple sites for glucose mobilization, enabling rapid energy release when needed, particularly during intense physical activity or fasting. Branching increases the surface area available for enzymes involved in breakdown or mobilization.

Glycogen Degradation

• Key Enzyme: Glycogen phosphorylase is the primary enzyme that cleaves glucose residues at alpha-1,4 bonds. It operates by using a phosphate group to maintain the phosphorylation status of the glucose moiety, producing glucose-1-phosphate. This reaction resembles synthetic steps and retains the stereochemistry (alpha configuration) of the glucose.

• Degrading Branched Glycogen: Since glycogen phosphorylase cannot cleave alpha-1,6 bonds, it reduces the chain's length by trimming the linear segments until three consecutive alpha-1,4 residues remain adjacent to a branch.

• These remaining residues can then be transferred to facilitate the elongation of a different chain. Afterward, a glycosidase hydrolyzes the alpha-1,6 link, releasing free glucose.

Function of Released Glucose

Released glucose can:

• Be exported from the liver into the bloodstream to maintain blood glucose levels for systemic energy needs.

• Be converted to glucose-6-phosphate to enter glycolytic pathways for ATP production.

• Serve various metabolic roles, including being utilized for energy in muscle contraction or being directed towards gluconeogenesis in times of fasting, thus contributing to overall glucose homeostasis in the body.