Glycogen Metabolism Control

REGULATED ENZYMES • Catalyzes rate-limiting step in glycogen synthesis • Active form: dephosphorylated • Inactive form: phosphorylated • Catalyzes rate-limiting step in glycogenolysis • Active form: phosphorylated • Inactive form: dephosphorylated • Activated by phosphorylase kinase • Activate form: phosphorylated • Inactive form: dephosphorylated KEY ORGANS • Regulates blood glucose, responds to needs of all organs • Insulin, glucagon & epinephrine receptors • 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) • 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 • Activates phosphoprotein phosphatase (PPP) • PPP dephosphorylates glycogen synthase (activates it) • PPP dephosphorylates phosphorylase kinase (inactivates it) • Upregulates glycogen synthesis, down regulates glycogenolysis 2. Allosteric regulation • Glycogen synthase activation: glucose 6P (glucose 1P --> glucose 6P) • Glycogen phosphorylase inhibition: glucose 6P, ATP (energy abundance) • Glycogen phosphorylase inhibition: glucose • Glycogen phosphorylase activation: Ca2+, AMP (low energy) • Muscle contraction: Ca2+ released from sarcolemma & allosterically activates phosphorylase kinase --> activates glycogen phosphorylase CLINICAL CORRELATION • Muscle glycogen phosphorylase deficiency • Glycogen accumulates in muscle • Muscle cramps & decreased exercise tolerance