Glycogen Metabolism (Lesson 5)

Glycogen: storage form of glucose

• Glycogen is the storage form of glucose, mainly in liver and muscle.
• It is a highly branched polymer that increases storage efficiency and provides rapid enzymatic access.

Glycogen structure

• Glucose units linked by $\alpha-1,4\text{-glycosidic}$ bonds; branch points via $\alpha-1,6\text{-glycosidic}$ bonds.
• Very large (103–105 glucose units) and less soluble than free glucose.
• Many non-reducing ends allow rapid synthesis and breakdown.

Glycogenesis (glycogen synthesis)

• Activation: glucose is converted to UDP-glucose using ATP and UTP (UDP-glucose pyrophosphorylase).
• Enzymes:
  • Glycogen synthase (GYS) extends the chain by adding glucose from UDP-glucose.
  • Glycogen branching enzyme (GBE) introduces new $\alpha-1,6$ branches.
  • Glycogenin serves as the primer for glycogen synthesis.
• Non-reducing ends are the sites of glucose addition/removal.

Glycogenolysis (glycogen breakdown)

• Glycogen phosphorylase cleaves $\alpha-1,4$ bonds to yield glucose-1-phosphate (G1P).
• Debranching enzyme (4:4 transferase and 1:6 glucosidase activities) resolves branches to produce G1P.
• Fate of G1P:
  • In liver: converted to glucose and released into blood via glucose-6-phosphatase (G6Pase).
  • In muscle: no glucose-6-phosphatase, so G6P remains for glycolysis within muscle.

Tissue distribution and roles

• Muscle glycogen: fuel for muscle activity; cannot raise blood glucose.
• Liver glycogen: maintains blood glucose; supplies glucose to all tissues.

Regulation and hormones

• Glucagon: stimulates glycogenolysis in liver (raises blood glucose).
• Insulin: promotes glycogenesis and glucose uptake in tissues (lowers blood glucose).
• In muscle, insulin enhances glucose uptake via GLUT4; liver regulates blood sugar via hormonal signals.

Enzymes and key steps (summary)

• UDP-glucose pyrophosphorylase: converts $\text{Glc-1-P}$ + $\text{UTP}$ to $\text{UDP-Glucose}$ + $\text{PPi}$.
• Glycogen synthase (GYS): adds glucose from UDP-glucose to the growing glycogen chain.
• Glycogenin: primer for polymer initiation.
• Branching enzyme (GBE): creates new $\alpha-1,6\text{ branches}$.

Glycogen branching and primer

• Glycogenin (GYG) initiates synthesis; GYS elongates; GBE forms $\alpha-1,6$ branches.

Glycogen vs starch

• Glycogen: highly branched for rapid glucose mobilization in animals.
• Starch: plant storage; less branching and more compact.

Glycogen storage diseases

• McArdle's disease: deficiency of glycogen phosphorylase (muscle);
• Cori (Cori disease): debranching enzyme deficiency;
• von Gierke's disease: glucose-6-phosphatase deficiency;
• Hers' disease: debranching enzyme deficiency (milder form).

Carbohydrate loading and endurance

• High carbohydrate intake before endurance events increases muscle glycogen stores and extends endurance time.

Quick recall

• Glucose is the main ATP fuel; glycogen stores glucose when blood levels are high.
• Glycogen comprises glucose units linked by $\alpha-1,4$ with $\alpha-1,6$ branches.
• Glycogenolysis vs glycogenesis are opposing processes regulated by hormones.
• Liver vs muscle glycogen differ in their ability to supply glucose to the body.
• Defects in glycogen metabolism cause glycogen storage diseases.