(emphasis on the Liver in comparison to Skeletal Muscle) - Glycogenesis vs Glycogenolysis

11

What is the primary role of the liver in glycogen metabolism

To maintain systemic blood glucose levels by storing and releasing glucose as needed

What is the primary role of skeletal muscle in glycogen metabolism

To provide local energy for contraction via glycolysis of stored glycogen

What key enzyme allows the liver to release free glucose into the bloodstream

Glucose-6-phosphatase

Why can’t skeletal muscle release glucose into the bloodstream

Skeletal muscle lacks glucose-6-phosphatase and glucagon receptors

What hormone strongly activates glycogenolysis in the liver

Glucagon

Why doesn’t glucagon activate glycogenolysis in skeletal muscle

Skeletal muscle does not express glucagon receptors (GPCR for glucagon)

Which hormone stimulates glycogenolysis in skeletal muscle

Epinephrine

What second messenger system does glucagon use in the liver

cAMP → PKA pathway

How does epinephrine affect liver glycogenolysis

Via both β-adrenergic (cAMP) and α1-adrenergic (Ca2+) signaling

How does epinephrine activate glycogenolysis in skeletal muscle

Via β-adrenergic receptors increasing cAMP and Ca2+ during contraction

What ion also activates phosphorylase kinase in skeletal muscle

Ca2+ via calmodulin during muscle contraction

How is glycogen synthase regulated in the liver

It is inactivated by phosphorylation (via PKA) and activated by dephosphorylation (via PP1)

What is the effect of insulin on liver glycogen metabolism

Activates glycogen synthase and inhibits glycogen phosphorylase via PP1

What is the insulin:glucagon ratio in a well-fed state

High

What happens to liver glycogen in a well-fed state

Glycogen synthesis is stimulated to store excess glucose

What happens to liver glycogen in a fasting state

Glycogenolysis is activated to maintain blood glucose

What is the primary fate of glucose-6-phosphate in the liver during fasting

Conversion to free glucose for export into the blood

What is the primary fate of glucose-6-phosphate in skeletal muscle during contraction

Enters glycolysis to make ATP

How sensitive is the liver to glucagon compared to insulin

The liver is ~1

Why is liver glycogen mobilized first during fasting

To maintain blood glucose levels for the brain and other organs

Why is muscle glycogen not used for blood glucose maintenance

Because it lacks the enzymes and receptors needed to export glucose

What molecule allosterically activates glycogen phosphorylase in skeletal muscle

AMP

Does AMP regulate liver glycogen phosphorylase

No

What cofactor enhances liver phosphorylase kinase activity during stress

Ca2+

What is the primary allosteric inhibitor of liver glycogen phosphorylase

Glucose

What is the main fate of glycogen-derived glucose in the liver

Export into blood to support glucose-dependent tissues

What is the main fate of glycogen-derived glucose in skeletal muscle

Oxidation via glycolysis for ATP production