Glycogen Degradation

Blood Glucose

Energy source that enters through diet and liver from glycogen breakdown or gluconeogenesis

• Catabolism

Stored Glycogen

Energy source where liver uses glucose residues in this to replenish blood glucose

• Muscle uses glucose residues in this for catabolism and to generate ATP

Stored Triacylglycerides in Adipose Tissue

Energy source that is mobilized mostly to muscle and liver for catabolism

• Amino acids — surplus, diet, protein breakdown

Common mechanism for cells to store excess metabolites

Polymerization into large macromolecular structures (polyphosphate, polyhydroxyalkanoate)

Liberation of Glucose from Glycogen Step 1

Release of Glucose-1-Phosphate

Liberation of Glucose from Glycogen Step 2

Remodeling to permit further degradation

Liberation of Glucose from Glycogen Step 3

Conversion of Glucose-1-Phosphate to Glucose-6-Phosphate

Glycogen Phosphorylase

Phosphorolysis of glycogen is catalyzed by this allosteric enzyme

Glycogen Breakdown

Uses phosphate, not water

• Glucose residue removed one by one from NON-REDUCING end

• Retains configuration at anomeric carbon

Glycogen Phosphorolysis

Yields glucose-1-phosphate; must prevent hydrolysis of glycogen

• No energy cost to feed into glycolysis

• Phosphorylation glucose stays in cell

Phosphoglucomutase

Exchanges phosphates between a serine residue within its own structure and a glucose-1-phosphate

Phosphorylase A

Glucose binding shifts the enzyme from the active form (R-state) to the less active form (T-state)

Phosphorylase B

Activated by high AMP

• Binds to a nucleotide binding site and stabilizes the R-state confirmation

• ATP and G6P act as negative allosteric effectors

Liver vs Muscle Cells

Standard states of the two cell types are opposite

• Leads to different resting activities and different direction of regulation

High [AMP]

Sign that muscle cells have low [ATP] and needs to carbonize glucose

• Active T-state binding

Phosphorylase Kinase Dual Control

1. Ca²⁺ Activation — Nerve impulse, muscle contraction, hormones

   • Partly Active

2. Protein Kinase A (Epinephrine) — Hormones

   • Fully Active

Activated glucose

Glycogen synthesis requires this for greater control

• Follow a separate pathway from degradation (even though it is the exact reverse reactions)

Glycosyl-Enzyme Intermediate

Transferase that can carry the transferred oligosaccharide to its new position before the second nucleophilic attack

Glycogen Synthase

Can only work on existing polymers

• Required priming with small oligosaccharides

• Accomplished by glycogenin dimer

• When glycogenin dimer comes together → cross-glycolysation builds up to an 8-sugar primer on opposing monomer

• This enzyme then takes over

1 ATP

Cost to regenerate UTP for the activation of glucose

• Rest of synthesis does NOT require energy input

More Active

Non-phosphorylase form of glycogen synthase

Phosphorylase B

This enzyme dampens the rate of breaking down glycogen into G1P

Phosphorylase A

This enzyme stimulates glycogen synthesis

Glycogen Synthase A

Is always active when dephosphorylated

Glycogen Synthase B

Is always active when phosphorylated