Biochemistry

Glycogen Metabolism Control

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REGULATED ENZYMES

Glycogen synthase: glucose 1P polymerization to glycogen

• Catalyzes rate-limiting step in glycogen synthesis
• Active form: dephosphorylated
• Inactive form: phosphorylated

Glycogen phosphorylase: releases glucose 1P residues from glycogen

• Catalyzes rate-limiting step in glycogenolysis
• Active form: phosphorylated
• Inactive form: dephosphorylated
• Activated by phosphorylase kinase

Phosphorylase kinase: phosphorylates glycogen phosphorylase

• Activate form: phosphorylated
• Inactive form: dephosphorylated

KEY ORGANS

Liver

• Regulates blood glucose, responds to needs of all organs
• Insulin, glucagon & epinephrine receptors

Skeletal muscle

• Synthesizes/breaks down glycogen based on own metabolic needs
• Only insulin and epinephrine receptors (NOT glucagon)

REGULATORY MECHANISMS

  1. Hormonal: insulin (high glucose), glucagon (low glucose) & epinephrine (stress)

Glucagon (low glucose) & epinephrine (stress):

• Activate protein kinase A (PKA) in cAMP-dependent manner
• PKA phosphorylates glycogen synthase (inactivates it)
• PKA phosphorylates phosphorylase kinase (activates it)
• Phosphorylase kinase phosphorylates glycogen phosphorylase (activates it)
• Upregulates glycogenolysis, down regulates glycogen synthesis

Insulin (elevated glucose):

• Activates phosphoprotein phosphatase (PPP)
• PPP dephosphorylates glycogen synthase (activates it)
• PPP dephosphorylates phosphorylase kinase (inactivates it)
• Upregulates glycogen synthesis, down regulates glycogenolysis

Glucagon receptor NOT in muscle: muscle only responds to stress (epinephrine)

  1. Allosteric regulation

Both hepatic and muscle cells

• Glycogen synthase activation: glucose 6P (glucose 1P –> glucose 6P)
• Glycogen phosphorylase inhibition: glucose 6P, ATP (energy abundance)

Liver only

• Glycogen phosphorylase inhibition: glucose

Muscle only

• Glycogen phosphorylase activation: Ca2+, AMP (low energy)
• Muscle contraction: Ca2+ released from sarcolemma & allosterically activates phosphorylase kinase –> activates glycogen phosphorylase

CLINICAL CORRELATION

McArdle’s Disease (Type V glycogen storage disease)

• Muscle glycogen phosphorylase deficiency
• Glycogen accumulates in muscle
• Muscle cramps & decreased exercise tolerance

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