Glycogenolysis

Summary

The body stores excess glucose as glycogen, which can be later mobilized to glucose via glycogenolysis.

Glycogen straight chains are broken down by glycogen phosphorylase. This enzyme cleaves alpha-1,4 bonds by the addition of phosphate, in the process releasing glucose-1-phosphate.

Phosphoglucomutase next converts glucose-1-phosphate to glucose-6-phosphate, which has a number of metabolic fates.

In the liver, glucose-6-phosphate can be converted to glucose and dumped into the bloodstream, thereby helping maintain blood-glucose levels.

Alternatively, glucose-6-phosphate can enter glycolysis and be used for energy. This is common in muscle, which mobilizes glycogen for bursts of energy.

Finally, glycogen branches are removed by glycogen debranching enzyme. We need glycogen debranching enzyme because glycogen phosphorylase can’t function within 4 residues of a glycogen branch point. These 4 residues are referred to as a limit dextrin, because they are the limit up to which glycogen phosphorylase can function.

At such a point, glycogen debranching enzyme moves the limit dextrin to a longer glycogen chain, at which point glycogen phosphorylase can function as usual. It moves all but the alpha-1,6 bonded glucose at the branch point, which glycogen debranching enzyme removes via hydrolysis. This hydrolysis of the branch point releases unmodified glucose, as opposed to releasing glucose-1-phosphate.

Key Points

• Glycogenolysis
  • Etymology
    • lysis=to cut
    • glycogenolysis= ‘to cut’ glycogen
  • Summary
    • Glycogenolysis mobilizes stored sugar (stored as glycogen)
      • Allows the organism to maintain sufficient blood glucose levels
    • Glycogen is a storage form of glucose
      • Branched polymer
        • Glucose molecules are linked in straight chains by alpha-1,4 bonds
        • Branch points off of those straight chains are linked by alpha-1,6 bonds
  • Location
    • Glycogen is primarily found in the liver and in skeletal muscle
      • Liver: to maintain blood glucose levels
      • Skeletal muscle: to meet exercise demands
    • Glycogen is stored in the cytoplasm of cells as granules
  • Reaction steps
    • Glycogen alpha-1,4-bonds → [glycogen phosphorylase] glucose-1-phosphate
      • Glycogen phosphorylase catalyzes the breakdown of glycogen straight chains 
        • Breaks alpha-1,4 bonds using inorganic phosphate
      • Glycogen phosphorylase cannot break down limit dextrins
        • The fragment that is 4 residues from a branch point
      • Irreversible (main regulatory step)
    • Glucose-1-phosphate → [phosphoglucomutase] glucose-6-phosphate
      • Phosphoglucomutase is an isomerase (Isomerization reaction)
      • Glucose-6-phosphate can enter glycolysis for energy production
        • Glucose-6-phosphate cannot diffuse into the bloodstream
          • Must be converted to glucose by glucose-6-phosphatase to diffuse into the bloodstream
    • Glycogen alpha-1,6-bonds → [Debranching enzyme] glucose
      • Debranching enzyme catalyzes the breakdown of glycogen branch points (limit dextrins)
        • First breaks alpha-1,4 bond nearest branch point and moves fragment to the main chain
          • Forms new alpha-1,4 bond on the straight chain
        • Then Breaks the alpha-1,6 bond at the branch point via hydrolysis
      • Produces glucose not glucose-6-phosphate
  • Regulation
    • Regulated based on energy needs
      • Glycogenolysis occurs when the body signals low blood glucose/a need for energy
    • Glycogen phosphorylase is the main regulatory step
    • Glycogenolysis speeds up (activation)
      • High energy need
        • AMP, epinephrine
      • low blood glucose levels
        • Glucagon
          • Glucagon etymology
            • Gluc = ‘glucose’ and agon = agonist
            • Glucagon means ‘glucose agonist’ so it increases blood glucose levels
    • Glycogenolysis slows down (inhibition)
      • low energy need
        • ATP