Glycogen Metabolism Notes

Glycogen Structure

  • Storage form of glucose, polymer linked by α-1,4 glycosidic bonds with α-1,6 branches every 12 residues.
  • Major stores in liver (10% by weight, maintains blood glucose) and muscle (2% by weight, meets energy needs).
  • Exists as granules containing ~55,000 glucose molecules.

Glycogen Degradation (Glycogenolysis)

  • Yields glucose 6-phosphate; requires four enzymes.
  • Phosphorylase: Key enzyme, cleaves glycogen at 1,4 position via phosphorolysis (addition of orthophosphate Pi), releasing glucose 1-phosphate.
    • Glycogen + Pi \leftrightarrow glucose \space 1-phosphate + glycogen \space (n-1 \space residues)
  • Debranching Enzyme: Required due to α-1,6 branches.
    • Transferase Activity: Shifts 3 glucosyl residues from one branch to another.
    • α-1,6-Glucosidase Activity: Hydrolyzes the α-1,6 linkage.
  • Phosphoglucomutase: Converts glucose 1-phosphate to glucose 6-phosphate.
  • Releasing Glucose from Liver:
    • Liver contains Glucose 6-phosphatase, which cleaves phosphoryl group from G-6P.
    • Glucose \space 6-phosphate + H20 \rightarrow glucose + Pi

Regulation of Phosphorylase Activity

  • Controlled by allosteric effectors (energy state) and reversible phosphorylation (hormones).
  • Liver: Exists mostly in active a form (R state); binding of glucose shifts it to inactive T state.
  • Muscle: Default state is inactive b form (T state); activated by AMP during contraction; glucose 6-phosphate stabilizes b form.
  • Hormonal Control: Glucagon (low blood glucose) and adrenaline (exercise) lead to phosphorylation and activation via Protein Kinase A (PKA).

Glycogen Synthesis (Glycogenesis)

  • Uses uridine diphosphate glucose (UDP-glucose) as activated glucose donor.
    • Glycogenn + UDP-glucose \rightarrow glycogenn+1 + UDP
    • Degradation: Glycogenn+1 + UDP + Pi \rightarrow glycogenn + glucose \space 1-phosphate
  • Glycogen Synthase: Key enzyme, transfers glucose from UDP-glucose to glycogen.
    • Can only add to polysaccharide with 4+ residues; requires glycogenin as a primer.
  • Branching Enzyme: Creates α-1,6 linkages by transferring 7 residues to create a new branch.
  • Glycogen synthase exists in active (a, non-phosphorylated) and inactive (b, phosphorylated) forms.

Regulation of Glycogen Metabolism

  • PKA phosphorylates Glycogen Synthase Kinase (GSK), turning it OFF.
  • Protein phosphatase 1 (PP1) reverses this process.
  • Effects of Insulin:
    • Stimulates glycogen production by inactivating glycogen synthase kinase.
    • Insulin receptor is a tyrosine kinase; phosphorylation recruits GLUT to the cell membrane.
    • PP1 dephosphorylates Glycogen Synthase (GS) to turn off the cycle.