USMLE

Glycogenesis

422 views
Biochemical Pathways
  1. Glycolysis
  2. Citric Acid Cycle (TCA Cycle)
  3. Electron Transport Chain (ETC)
  4. Cori Cycle
  5. De Novo Purine Synthesis
  6. De Novo Pyrimidine Synthesis
  7. Purine Salvage
  8. Purine Excretion
  9. Ethanol Metabolism
  10. Pyruvate Metabolism
  11. HMP Shunt (Pentose Phosphate Pathway)
  12. Galactose Metabolism
  13. Sorbitol (Polyol) Pathway
  14. Urea Cycle
  15. Alanine (Cahill) Cycle
  16. Catecholamine Synthesis & Breakdown
  17. Homocysteine Metabolism
  18. Fatty Acid Synthesis (Citrate Shuttle)
  19. Fatty Acid Breakdown (Carnitine Shuttle)
  20. Propionic Acid Pathway
  21. Fructose Metabolism
  22. Regulation by Fructose-2,6-Bisphosphate (F-2,6-BP)
  23. Glycogenesis

Summary

Glycogenesis is the biochemical pathway that produces glycogen, which is the body’s storage form of glucose. The main places in our body that want to store glucose for later use as glycogen are the liver and muscle. 

Glycogenesis begins with glucose-6-phosphate, which is then catalyzed to glucose-1-phosphate via a mutase enzyme, phosphoglucomutase.

Next, Glucose-1-phosphate reacts with UTP to form the high-energy UDP-glucose intermediate, in a reaction catalyzed by a pyrophosphorylase enzyme, UDP-glucose pyrophosphorylase.

Next, glycogen synthase uses the energy from UDP-glucose to connect the glucose residue to the end of a glycogen straight chain. When extending a straight chain, glucose molecules are added via alpha-1,4 linkages. Glycogen synthase is stimulated by insulin, but is inhibited by glucagon and epinephrine.

Finally, glycogen achieves its branched structure due to the actions of glycogen branching enzymes. These enzymes break off the ends of a glycogen straight chain and attach the fragment to the side of a straight chain to form a branch point, which is formed via an alpha-1,6 linkage.

Key Points

  • Glycogenesis
    • Etymology
      • Glycogenesis = glycose + genesis
        • Glycose = old term for glucose
        • Genesis = the generation / making of
    • Summary
      • Glycogenesis stores excess sugar as glycogen
        • Allows the organism to store up fuel to prepare for future energy needs
        • Glycogen is a storage form of polymerized sugar that appears as clear cytoplasmic granules
        • Glycogen stains pink/purple with the PAS reaction
      • Glycogen is a branched polymer
        • Branching increases solubility of glycogen in aqueous environment of cell, and adds more terminal residues (where reactions can occur)[a][b]
          • Increases rate of glycogen formation and breakdown
        • Straight chains formed by alpha-1,4 bonds
        • Branch points formed by alpha-1,6 bonds
      • Glycogen primarily found in the liver and skeletal muscle
        • Liver: to store glucose for later release
        • Skeletal muscle: to store energy for later consumption by exercise
    • Reaction Pathway
      • Glucose → Glucose-6-Phosphate (G6P)
        • Via Hexokinase/Glucokinase
        • Shared step in common with Glycolysis
      •  Glucose-6-Phosphate (G6P) → Glucose-1-Phosphate (G1P)
        • Via Phosphoglucomutase
        • Phosphoglucomutase is an isomerase
      • Glucose-1-Phosphate (G1P) → UDP-glucose
        • Via UDP-glucose pyrophosphorylase
        • Consumes 1 UTP as its energy source to link UDP to glucose, releasing a pyrophosphate
          • PPi (pyrophosphate) is quickly metabolized to form two Pi (inorganic phosphates)
          • This drives the reaction forward (Le Chatelier's principle)
      • UDP-glucose → Glycogen (straight chain)
        • Via Glycogen synthase
        • Creates straight chain alpha-1,4 bonds
        • Glycogen is synthesized from UDP-glucose--glucose that has been ‘charged’ with energy from UTP
        • Irreversible (main regulatory step)
      • Glycogen (straight chain) → Glycogen (branched form)
        • Via Branching enzyme
        • Catalyzes the formation of glycogen branches
          • Breaks alpha-1,4 straight chain bond
            • By hydrolysis
          • Attaches the fragment to the side of the chain with an alpha-1,6, bond
            • This creates a branch
    • Regulation
      • Glycogen synthase reaction is the primary regulatory step
        • Stimulated by insulin
          • Representative of fed state (high glucose)
          • Insulin stimulates protein phosphorylase, which activates glycogen synthase by dephosphorylation
          • Goal is to store glucose as energy for later use
        • Inhibited by glucagon and epinephrine
          • Representative of fasting state (low glucose)
          • Do not want to produce glycogen stores when the body is already in a low glucose state