Glycogen Degradation

Glycogen is a large, branched polymer of glucose residues, primarily linked by α(1→4) bonds, with branching occurring approximately every 12th glucose via α(1→6) bonds.
It serves as a key energy source for runners due to its ability to be mobilized quickly.
Only 2% of muscle mass contains glycogen; however, the liver has a 10% concentration.
Glycogen keeps blood glucose levels stable between meals, especially important for brain function, as glucose is a primary fuel for the brain.

Efficient glycogen breakdown involves four key enzymatic activities:
- Glycogen phosphorylase: Degrades glycogen to form glucose 1-phosphate.
- Debranching enzyme: Converts branched structures to linear ones to facilitate further breakdown.
- Transferase: Moves glucosyl residues within the glycogen molecule.
- Phosphoglucomutase: Converts glucose 1-phosphate to glucose 6-phosphate.

Glycogen phosphorylase cleaves glycosidic bonds via phosphorolysis, yielding glucose 1-phosphate.
This reaction is energetically favorable since glucose 1-phosphate is already phosphorylated, eliminating the need for ATP consumption.

Cannot cleave α(1→6) bonds at branch points; therefore, other enzymes are required to manage these branches.
The debranching enzyme hydrolyzes these bonds releasing free glucose.

Allosteric Regulation and Phosphorylation: Glycogen phosphorylase is modulated by:
- Allosteric effectors reflecting the energy state of the cell (e.g., AMP, ATP).
- Reversible phosphorylation primarily in response to glucagon and epinephrine.
Two isozymes exist:
- Liver phosphorylase (phosphorylase a): Default is active form; inhibited by glucose.
- Muscle phosphorylase (phosphorylase b): Default is inactive; activated in response to AMP during muscle contraction.

Protein kinase A activation: Triggered by glucagon and epinephrine through a G-protein-coupled pathway leading to the activation of phosphorylase kinase.
Elevated cAMP levels lead to rapid mobilization of glucose from glycogen stores.

Epinephrine: Primarily stimulates glycogen breakdown in muscle for immediate energy needs during exertion.
Glucagon: Signals the liver to release glucose when energy availability is low (e.g., during fasting).
Both hormones bind to 7TM receptors, activating a signal cascade that amplifies responses for rapid glucose release.

Depletion of glycogen stores correlates with onset of fatigue, known as "hitting the wall".
Studies indicate that metabolic products like ADP may be more directly linked to fatigue than glycogen depletion itself.

Hers Disease: Deficiency in liver glycogen phosphorylase, leading to glycogen accumulation, hepatomegaly, and hypoglycemia. Variable symptoms among patients.
McArdle's Disease: Caused by a lack of skeletal muscle glycogen phosphorylase; leads to exercise-induced muscle pain and rhabdomyolysis.

Type I (slow-twitch): Energy from fatty acids; low glycogen phosphorylase activity.
Type IIb (fast-twitch): High glycogen and phosphorylase activity; utilizes glucose quickly for bursts of power.
Type IIa fibers: Intermediate features; can adapt to training for oxidative or glycolytic performance.

Glycogen metabolism is intricately regulated by hormonal signals, cellular energy states, and specific enzyme activities, playing a crucial role in energy management during physical activity, and its malfunction can lead to significant metabolic diseases.