U01.01.115 Glycogen regulation by insulin and glucagon/epinephrine

Glycogen metabolism plays a crucial role in regulating glucose levels in the body, and it is tightly controlled by insulin, glucagon, and epinephrine. Understanding how these hormones interact with key enzymes involved in glycogen synthesis and breakdown is essential for USMLE Step 1 preparation.

Key Enzymes and Regulatory Pathways

Glycogen Phosphorylase: Breaks down glycogen into glucose-1-phosphate.
Glycogen Synthase: Involved in glycogen synthesis, converting glucose-1-phosphate to glycogen.
Glycogen Phosphorylase Kinase: Activates glycogen phosphorylase by phosphorylation.
Protein Kinase A (PKA): Activated by cAMP and phosphorylates key enzymes involved in glycogen breakdown and synthesis.
Protein Phosphatase: Dephosphorylates enzymes, leading to activation or deactivation of glycogen metabolism.
Calcium-Calmodulin: Activates phosphorylase kinase in muscle during contraction.

Hormonal Regulation of Glycogen Metabolism

Hormone	Effect on Glycogen Metabolism	Target Tissues	Mechanism of Action
Insulin	Promotes glycogen synthesis and inhibits glycogen breakdown	Liver and muscle	Activates glycogen synthase, inhibits glycogen phosphorylase, and promotes dephosphorylation via protein phosphatase.
Glucagon	Promotes glycogen breakdown and inhibits glycogen synthesis	Liver	Activates adenylate cyclase, increases cAMP, activates PKA, which phosphorylates and activates glycogen phosphorylase.
Epinephrine	Stimulates glycogen breakdown and inhibits glycogen synthesis	Liver and muscle	Activates adenylate cyclase and increases cAMP, similar to glucagon; also increases calcium in muscle, activating phosphorylase kinase.
Calcium	Activates glycogen breakdown in muscle during contraction	Muscle	Binds to calmodulin, which activates phosphorylase kinase.
cAMP	Activates PKA	Liver and muscle	Activates PKA, which phosphorylates enzymes involved in glycogen breakdown.

Points to Remember

Insulin promotes glycogen storage and inhibits its breakdown, primarily in the liver and muscle.
Glucagon stimulates glycogen breakdown in the liver by activating the cAMP-PKA pathway.
Epinephrine mimics glucagon’s effects in the liver and muscle but also activates muscle glycogen breakdown through calcium signaling during muscle contraction.
Protein Kinase A (PKA) is a central regulator of glycogen metabolism, activated by cAMP and epinephrine.
Calcium-calmodulin signaling is essential for glycogen breakdown in muscle during contraction.
The Receptor Tyrosine Kinase mechanism is involved in insulin signaling, promoting the dephosphorylation of enzymes that favor glycogen synthesis.

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USMLE Step 1 Review Series

Curriculum

U01.01.115 Glycogen regulation by insulin and glucagon/epinephrine

Key Enzymes and Regulatory Pathways

Hormonal Regulation of Glycogen Metabolism

Points to Remember

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