TOPIC 1.3 - 1.4 - Carbohydrate Metabolism - Glycogen Synthesis Degradation

Glycogen Synthesis, Degradation and Reciprocal Regulation

Dr. Nigel Austin

Page 1: Overview of Glycogen

  • Glycogen is a storage form of glucose.

  • Composed of long glucose polymers with approximately 10 residues per branch.

  • Contains two primary types of bonds:

    • α - 1,4 glycosidic bonds: Found in the backbone.

    • α - 1,6 glycosidic bonds: Located at the branch points.

  • Branching in glycogen allows for rapid breakdown due to multiple terminal ends, enabling quick energy release.

Page 2: Importance of Glycogen Storage

  • Storage Sites: Primarily stored as granules in the cytoplasm of liver cells (hepatocytes).

  • Function: Helps regulate blood glucose concentration, crucial for tissues, especially the brain and erythrocytes which rely heavily on glucose for energy.

  • Muscle Storage: Stored in skeletal and cardiac muscle cells, quickly mobilized during sudden or strenuous activities to provide energy.

Page 3: Glycogen Breakdown (Glycogenolysis)

  • Process Overview: Glycogen breakdown is termed glycogenolysis and occurs in three main steps using four different enzymes.

Page 4: Glycogenolysis – Step 1: Phosphorylysis

  • Definition: The first step involves phosphorolysis, the cleavage of a terminal glucose residue from glycogen.

  • Key Enzyme: Glycogen phosphorylase recognizes and removes the free -OH group on terminal glucose residues, adding inorganic phosphate (Pi), resulting in glucose-1-phosphate.

Page 5: Glycogenolysis – Step 2: Glycogen Remodeling

  • Limitation of Glycogen Phosphorylase: Can only cleave α - 1,4 glycosidic bonds and stops 4 residues before the branch point.

  • Enzyme Activation: At this stage, a bifunctional debranching enzyme is needed:

    • Transferase Activity: Moves 3 glucose residues to another terminal end.

    • α - 1,6 Glycosidase Activity: Cleaves the glucose residue at the branch point into a free glucose molecule.

Page 6: Glycogenolysis – Step 3: Conversion of Glucose-1-Phosphate

  • Final Step: The enzyme phosphoglucomutase converts glucose-1-phosphate into glucose-6-phosphate.

Page 7: Glycogenesis - Glycogen Synthesis

  • Requirement: Synthesis (glycogenesis) of glycogen needs a primer.

  • Primer Formation: Glycogenin synthesizes a primer of 7 glucose residues using UDP-glucose.

  • Elongation: After primer formation, glycogen synthase extends the glucose chain using α - 1,4 glycosidic bonds, while branching enzyme introduces α - 1,6 glycosidic bonds.

Page 8: Reciprocal Regulation of Glycogen

  • Glucagon's Role: Glycogen degradation stops glycogen synthesis.

  • Insulin's Role: Insulin prevents glycogen degradation by:

    • Inhibiting the phosphorylation and activation of glycogen phosphorylase.

    • Activating phosphodiesterase which converts cAMP to AMP, reversing glucagon's effects.

Page 9: WACE Questions (Assessment)

  1. Main Function: Why store glucose as glycogen rather than free glucose? (1 mark)

  2. Glycogen Remodeling: Purpose of glycogen remodelling? (2 marks)


  3. Fate of Glucose-6-Phosphate: a) In liver cells? (2 marks)b) In active muscle cells? (2 marks)

  4. Anaerobic Conditions: Pathway for ATP release from glycogen and its final product during rapid activity? (1 mark)

  5. Catabolism: What compound are amino acids and fats catabolized into for energy release? Which pathways metabolize this compound? (2 marks)

  6. Importance of Glycogen Breakdown: Why is glycogen breakdown essential in skeletal muscles compared to fats and amino acids? (2 marks)

    • Example context: Running away from an enraged dog.