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Overview of Glycogen Metabolism

Oct 27, 2024

Lecture on Glycogen Metabolism (Chapter 11 - Lippincott's Biochemistry)

Introduction

  • Glycogen: A storage form of glucose, essential for maintaining blood glucose levels.
  • Importance of Glucose: Critical for brain function, certain cells, and muscles.
  • Sources of Glucose:
    • Diet
    • Glycogen degradation
    • Gluconeogenesis (slower production)

Glycogen Structure

  • Main Storage Areas: Skeletal muscle (for energy during exercise) and liver (maintains glucose levels during fasting).
  • Structure:
    • Branch-like, with alpha 1,4 linkages (linear) and alpha 1,6 linkages (branching).
    • Made from alpha-D glucose.

Glycogenesis (Synthesis of Glycogen)

  • Process:
    • Steps:
      1. Glucose 6-phosphate → Glucose 1-phosphate.
      2. Glucose 1-phosphate + UTP → UDP-glucose (enzyme: UDP glucose phosphorylase).
      3. Glycogen synthase adds glucoses forming alpha-1,4 linkages.
      4. Glycogenin acts as a primer for initial glucose attachment.
    • Branching Enzyme (4,6-transferase):
      • Creates alpha-1,6 branches by moving glucose units.
    • Energy Requirement: Uses ATP and UTP.

Glycogenolysis (Breakdown of Glycogen)

  • Process:
    • Glycogen phosphorylase breaks down glycogen, releasing glucose 1-phosphate.
    • Debranching Enzymes:
      • 4-to-4 transferase moves glucose residues.
      • Amylo-alpha-1,6-glucosidase releases free glucose.
    • Final product: Glucose 1-phosphate → Glucose 6-phosphate.
  • Tissue-Specific Pathways:
    • Liver: Uses glucose 6-phosphatase to release glucose.
    • Muscles: Utilize glucose for ATP, no need for glucose 6-phosphatase.

Regulation of Glycogenesis and Glycogenolysis

  • Hormonal Regulation:
    • Glucagon & Epinephrine: Promote glycogen breakdown (via adenyl cyclase system, CAMP, and protein kinases).
    • Insulin: Promotes glycogen synthesis and inhibits breakdown.
  • Allosteric Regulation:
    • High AMP & low glucose activate glycogen phosphorylase for breakdown.
    • Abundance of nutrients inhibits breakdown.
  • Calcium in Muscles: Activates glycogen breakdown via calmodulin.

Glycogen Storage Diseases

  • Genetic Disorders:
    • Issues with glycogen breakdown or formation.
    • Symptoms include hypoglycemia and muscle weakness.
    • Severity varies based on tissue affected.

Conclusion

  • Summary of glycogen metabolism with a flowchart.
  • Encouragement to review questions and answers.

Note: This lecture is a simplified overview; refer to the textbook for in-depth details on enzymes and pathways involved in glycogen metabolism.

Full transcript