Glycogenolysis is the process of breaking down glycogen into glucose to provide immediate energy.
Glycogen is a multi-branched polysaccharide that serves as a primary form of energy storage in animals and fungi. It is mainly stored in the liver and muscle tissues. Here’s a detailed overview of glycogen:
Structure
- Polysaccharide Composition: Glycogen is composed of glucose molecules linked together primarily by α-1,4-glycosidic bonds with branches formed by α-1,6-glycosidic bonds.
- Highly Branched: The structure of glycogen is highly branched, with branches occurring approximately every 8-12 glucose units. This branching allows for rapid release of glucose when it is needed.
Storage Sites
- Liver: The liver stores glycogen and releases glucose into the bloodstream to maintain blood glucose levels, especially between meals or during fasting.
- Muscle: Muscle glycogen is used locally within the muscle cells to provide energy during physical activity.
Here’s a step-by-step breakdown of the glycogenolysis process:
Step 1: Glycogen Phosphorylase Activation
- Enzyme: Glycogen phosphorylase
- Reaction: Glycogen (n units) + Pi (inorganic phosphate) → Glycogen (n-1 units) + Glucose-1-phosphate
- Mechanism: Glycogen phosphorylase cleaves α-1,4-glycosidic bonds at the non-reducing ends of glycogen, releasing glucose-1-phosphate (G1P).
Step 2: Debranching Enzyme Activity
- Enzymes:
- Oligo-α-1,4-α-1,4-glucantransferase (transferase activity)
- Amylo-α-1,6-glucosidase (glucosidase activity)
- Reaction:
- Transferase moves a small oligosaccharide near a branch point to a longer chain.
- Glucosidase then hydrolyzes the α-1,6-glycosidic bond, releasing free glucose.
- Mechanism: When glycogen phosphorylase reaches about four glucose residues from a branch point, the debranching enzyme transfers a trisaccharide from the branch to the main chain and then cleaves the remaining single glucose residue at the α-1,6 linkage.
Step 3: Conversion of Glucose-1-Phosphate to Glucose-6-Phosphate
- Enzyme: Phosphoglucomutase
- Reaction: Glucose-1-phosphate → Glucose-6-phosphate
- Mechanism: Phosphoglucomutase catalyzes the reversible conversion of G1P to glucose-6-phosphate (G6P) via an intermediate glucose-1,6-bisphosphate.
Step 4: Final Conversion to Glucose (Liver-specific)
- Enzyme: Glucose-6-phosphatase
- Reaction: Glucose-6-phosphate + H₂O → Glucose + Pi
- Mechanism: In the liver, G6P is hydrolyzed by glucose-6-phosphatase to free glucose, which can be released into the bloodstream to maintain blood glucose levels.
Regulation of Glycogenolysis
- Hormonal Regulation:
- Glucagon: Activates glycogen phosphorylase in the liver in response to low blood glucose levels.
- Epinephrine: Activates glycogen phosphorylase in both liver and muscle during stress or exercise.
- Covalent Modification:
- Phosphorylation: Glycogen phosphorylase is activated by phosphorylation. This modification is mediated by phosphorylase kinase, which is itself activated by protein kinase A (PKA) in response to cAMP signaling.
- Dephosphorylation: Glycogen phosphorylase is inactivated by dephosphorylation, which is mediated by protein phosphatase 1 (PP1).
Summary
- Glycogen phosphorylase cleaves α-1,4-glycosidic bonds, releasing G1P.
- Debranching enzyme rearranges and removes branches.
- Phosphoglucomutase converts G1P to G6P.
- Glucose-6-phosphatase in the liver converts G6P to glucose for blood release.
This process ensures that glucose is readily available for energy production, especially during fasting or intense physical activity.