Chapter 24: Glycogen Degradation

Glycogen

A highly branched homopolymer of glucose stored in liver and muscle; serves as a glucose reserve.

Liver glycogen function

Maintains blood glucose levels during fasting by releasing glucose into the blood.

Muscle glycogen function

Provides energy for muscle contraction during exercise; energy source not dependent on oxygen.

Glycogen storage location

Cytoplasmic granules within cells.

Glycogen straight chains

Connected by α-1,4-glycosidic bonds.

Glycogen branches

Occur every ~10 residues via α-1,6-glycosidic bonds.

Glycogenin

Core protein that initiates glycogen synthesis.

Nonreducing ends of glycogen

Sites where glycogen phosphorylase acts; contain free –OH groups.

Number of enzymes required for glycogen breakdown

Four enzyme activities.

Enzyme 1 (Glycogen phosphorylase)

Degrades glycogen to release glucose 1-phosphate by cleaving α-1,4-glycosidic bonds using orthophosphate.

Glycogen phosphorylase reaction type

Phosphorolysis, not hydrolysis.

Energy use in glycogen phosphorylase reaction

No ATP required; phosphate already added.

Enzyme 2 (Transferase)

Moves a small oligosaccharide (3 residues) from a branch to a nearby chain to allow further degradation.

Enzyme 3 (α-1,6-glucosidase)

Debranching enzyme that hydrolyzes α-1,6 bonds to release free glucose.

Enzyme 4 (Phosphoglucomutase)

Converts glucose 1-phosphate to glucose 6-phosphate via a glucose 1,6-bisphosphate intermediate.

Hexokinase/Glucokinase

Phosphorylates free glucose (from α-1,6-glucosidase reaction) to glucose 6-phosphate.

Liver enzyme for free glucose release

Glucose 6-phosphatase; converts glucose 6-phosphate to free glucose for blood export.

Glucose 6-phosphatase presence

Found in liver; absent in most other tissues.

Glycogen phosphorylase regulation

Controlled by allosteric effectors and reversible phosphorylation.

Phosphorylase forms

Less active b form (dephosphorylated) and more active a form (phosphorylated).

R and T states

R (relaxed, active) and T (tense, inactive) conformations of phosphorylase enzyme.

Phosphorylase a form

Favors R state; serine phosphorylated; active site accessible.

Phosphorylase b form

Favors T state; serine unphosphorylated; active site blocked.

Muscle phosphorylase default state

b form in T state (inactive).

Muscle phosphorylase activation

AMP binds and shifts enzyme to R state when energy is needed.

Muscle phosphorylase inhibition

ATP and glucose 6-phosphate stabilize T state when energy is abundant.

Epinephrine effect on muscle

Converts phosphorylase b to active a form regardless of AMP, ATP, or G6P levels.

Liver phosphorylase default state

a form in R state (ready to release glucose).

Liver phosphorylase regulation

Glucose acts as a negative regulator, shifting enzyme to T state; not regulated by AMP.

Hormonal regulation in liver

Glucagon and epinephrine activate (phosphorylation); insulin deactivates (dephosphorylation).

Phosphorylase kinase function

Converts phosphorylase b to a form by phosphorylation.

Phosphorylase kinase activation

Activated by phosphorylation (via PKA) and Ca2+ binding; fully active when both signals present.

Phosphorylase kinase δ subunit

Calmodulin, the calcium sensor.

Glucagon

Hormone of fasting; stimulates liver glycogen breakdown.

Epinephrine (adrenaline)

Hormone of exercise; stimulates muscle glycogen breakdown.

G-protein cascade in glycogenolysis

Glucagon/epinephrine activate G-proteins → cAMP → PKA → phosphorylase kinase → phosphorylase a → glycogen breakdown.

Calcium in muscle

Released during contraction; activates phosphorylase kinase.

Calcium in liver

Released via α-adrenergic receptor stimulation by epinephrine; activates phosphorylase kinase.

Glycogen depletion and fatigue

Fatigue coincides with glycogen depletion; likely due to signaling (lactate, protons, glucose, Ca2+) rather than energy shortage.