Mechanism of Glycogen Breakdown
The mobilization process involves the sequential cleavage of carbohydrate residues from the polymer chain. The primary role is performed by glycogen phosphorylase. This enzyme breaks $\alpha$-1,4-glycosidic bonds, releasing molecules as glucose-1-phosphate.
However, phosphorylase cannot act on the branching points of the molecule ($\alpha$-1,6-bonds). These are addressed by amylo-1,6-glucosidase (debranching enzyme). It performs a hydrolysis reaction—cleaving the single residue at the branch point with the participation of water. This yields unphosphorylated free glucose.
After "debranching," glycogen phosphorylase resumes cleaving glucose-1-phosphate from the straightened chain. In the next step, the resulting glucose-1-phosphate is isomerized into glucose-6-phosphate, the ultimate fate of which depends on the tissue type.
Differences in Mobilization Between the Liver and Muscles
Although the initial stages of glycogenolysis are universal, the ultimate goal of the process differs fundamentally between these organs due to their enzymatic profile.
- In the liver, a unique enzyme is present: glucose-6-phosphatase. It removes the phosphate group from glucose-6-phosphate, converting it into free glucose. These molecules enter the bloodstream, maintaining normal glycemia (3.3–5.5 mmol/L) and nourishing other tissues, most notably the brain.
- In muscles, the enzyme glucose-6-phosphatase is absent. The phosphorylated glucose-6-phosphate molecule cannot cross the cell membrane. Therefore, all the carbohydrate remains inside the muscle cell and enters the catabolic pathway (glycolysis) to meet its own energy demands during contraction.
Hormonal Regulation (Adenylyl Cyclase Cascade)
The switch between glycogen synthesis and breakdown depends on the insulin-glucagon ratio. When this ratio drops (during the postabsorptive state), mobilization is triggered. In the liver, the process is activated by glucagon, while in both the liver and muscles, it is activated by epinephrine.
The hormone binds to receptors and initiates the adenylyl cyclase cascade, which operates via chemical modification (phosphorylation) of enzymes:
- Protein kinase A is activated.
- It phosphorylates inactive phosphorylase kinase, converting it to its active form.
- Phosphorylase kinase, in turn, phosphorylates glycogen phosphorylase.
- Active glycogen phosphorylase begins actively breaking down glycogen.
Crucially, this same phosphorylation process converts the synthesis enzyme (glycogen synthase) into an inactive state. Thus, the cascade simultaneously triggers carbohydrate breakdown and inhibits their synthesis.
Regulation by Muscle Contraction
In skeletal muscle, glycogenolysis is additionally stimulated directly by muscle activity. Contraction releases $Ca^{2+}$ ions, which bind to the protein calmodulin.
The resulting "$4Ca^{2+}$-calmodulin" complex can directly activate phosphorylase kinase and other calmodulin-dependent protein kinases. As a result, glycogen phosphorylase transitions into its active form even without epinephrine signaling, ensuring high-intensity energy production.
Restoration of the system to its basal state (upon eating or resting) is mediated by phosphodiesterase (which degrades cAMP) and phosphoprotein phosphatase (which dephosphorylates all activated enzymes).