Regulation of Glycogen Metabolism
1. Key Concept
- Glycogen metabolism is regulated so that glycogen synthesis (glycogenesis) and glycogen breakdown (glycogenolysis) do not happen at the same time.
- Regulation depends on:
- Hormones
- Energy status of the cell
- Allosteric control
- Covalent modification (phosphorylation/dephosphorylation)
2. Key Enzymes (Opposing Pair)
- Glycogen Synthase → Builds glycogen.
- Glycogen Phosphorylase → Breaks glycogen.
These enzymes are reciprocally regulated:
- When one is ON, the other is OFF.
3. Hormonal Regulation
A. Insulin (Fed state — high blood glucose)
- Stimulates glycogen synthesis.
- Activates glycogen synthase (dephosphorylation makes it active).
- Inhibits glycogen phosphorylase.
- Occurs in both liver and muscle.
Effect: Store extra glucose as glycogen.
B. Glucagon (Fasting state — low blood glucose)
- Works only in liver.
- Activates protein kinase A → phosphorylates:
- Glycogen phosphorylase → ON (breakdown)
- Glycogen synthase → OFF
- Increases release of glucose into blood.
Effect: Maintain blood glucose levels during fasting.
C. Epinephrine (Stress / Exercise)
- Acts in both muscle and liver.
- In muscle, epinephrine increases glycogen breakdown → ATP for contraction.
- In liver, epinephrine supports glucagon in increasing blood glucose.
4. Allosteric (Energy Status) Regulation
In Muscle
- AMP activates glycogen phosphorylase → breakdown for ATP.
- ATP and Glucose-6-phosphate inhibit glycogen phosphorylase (when energy is
- sufficient).
- Ca²⁺ (released during muscle contraction) activates phosphorylase kinase → stimulates glycogen breakdown even without hormones.
In Liver
- Glucose inhibits glycogen phosphorylase, helping switch to storage mode after meals.