Glycogen Metabolism Notes

Glycogen Structure

  • Glycogen is a polymer of glucose residues linked by α-(1,4)- and α-(1,6)-glycosidic bonds.
  • Branches occur after 8-10 glucosyl residues with α(1→6) linkages.
  • Main stores are in skeletal muscle and liver.

Glycogen Function

  • Liver Glycogen: Maintains blood glucose concentration, especially during early fasting (12-18 hours).
  • Muscle Glycogen: Energy source within the muscle during contractions; unavailable to other tissues due to lack of glucose-6-phosphatase.

Energy Storage

  • Glycogen is mobilized to energy faster than fat.
  • Fatty acids cannot be metabolized anaerobically.
  • Fat cannot convert to glucose to maintain blood glucose levels.

Glycogenesis (Glycogen Synthesis)

  • Occurs in the cytosol of liver and muscle, requiring ATP and UTP.

Steps:

  1. UDP-glucose synthesis:

    • Hexokinase (muscle) & glucokinase (liver): glucose → glucose 6-phosphate

  2. Phosphoglucomutase: glucose 6-phosphate → glucose 1-phosphate

  3. UDP-glucose pyrophosphorylase: glucose 1-phosphate + UTP → UDP-glucose + PPi

    glucose−1−phosphate+UTP→UDP−glucose+PPiglucose-1-phosphate + UTP \rightarrow UDP-glucose + PP_i

  4. Primer synthesis:

    • Glycogenin acts as a primer, catalyzing the addition of initial glucose residues from UDP-glucose.
    • Tyrosine hydroxyl group on glycogenin is the attachment site.

  5. Elongation:

    • Glycogen synthase extends the chain via α(1→4) linkages.

  6. Branching:

    • Branching enzyme amylo-α(1→4) → α(1→6)-transglucosidase transfers 6-8 glucosyl residues to create branches.

Glycogenolysis (Glycogen Breakdown)

  • Via glycogen phosphorylase and debranching enzyme.

Steps:

  1. Phosphorylase Action:

    • Glycogen phosphorylase cleaves α(1→4) glycosidic bonds, releasing glucose 1-phosphate.
    • Pyridoxal phosphate (B6) is a required coenzyme.
    • Inhibited by insulin, stimulated by glucagon.

    Glycogen<em>(nresidues)+P</em>i→Glycogen(n−1<br/>residues)+glucose−1−phosphateGlycogen<em>{(n \newline residues)} + P</em>i \rightarrow Glycogen_{(n-1 <br />\newline residues)} + glucose-1-phosphate

  2. Debranching Enzyme:

    • Transfers outer 3 of 4 glucosyl residues at a branch to another chain (oligo-α(1→4)→α(1→4)-glucan transferase).
    • Removes the remaining glucose via α(1→6)-glucosidase activity, releasing free glucose.

  3. glucose-1-phosphate is converted to glucose-6-phosphate by phosphoglucomutase

  4. Glucose 6-phosphate to glucose by Glucose 6- phosphatase (in liver only )

Regulation of Glycogen Metabolism

  • Allosteric control and hormonal regulation.

Allosteric Regulation:

  • Well-fed state: Glycogen synthase activated by glucose 6-phosphate.
  • Glycogen phosphorylase inhibited by glucose 6-phosphate and ATP.
  • Muscle contraction: Ca2+ release activates phosphorylase kinase via calmodulin.
  • Anoxia/ATP depletion: AMP activates glycogen phosphorylase.

Hormonal Regulation:

  • Glucagon and epinephrine stimulate glycogen degradation via protein kinase activation.
  • cAMP-directed pathway: Glucagon (liver) and epinephrine (muscle) activate adenylyl cyclase, increasing cAMP, which activates protein kinase, inactivating glycogen synthase.
Hormonal Effects
  • Glucagon:
    • Released during low glucose levels, acts on the liver.
    • Stimulates glycogen breakdown, inhibits glycogenesis, blocks glycolysis, and stimulates gluconeogenesis.
  • Epinephrine:
    • Released during low glucose levels, acts on skeletal muscle.
    • Stimulates glycogen breakdown and inhibits glycogenesis.
  • Insulin:
    • Released during high glucose levels from pancreatic β-cells.
    • Increases glycogenesis in muscle and liver.