Gluconeogenesis is a critical metabolic pathway that ensures the body maintains stable blood glucose levels during fasting, prolonged exercise, or any situation where dietary glucose is not readily available.
It occurs mainly in the liver and kidneys.
Gluconeogenesis Pathway
1. Pyruvate to Phosphoenolpyruvate (PEP):
Pyruvate Carboxylase converts pyruvate to oxaloacetate (requires biotin, activated by acetyl-CoA).
PEP Carboxykinase (PEPCK) converts oxaloacetate to PEP (occurs in mitochondria or cytosol).
Lactate can enter this pathway after conversion to pyruvate.
2. Fructose-1,6-bisphosphate to Fructose-6-phosphate:
Catalyzed by fructose-1,6-bisphosphatase, bypassing glycolytic enzyme PFK-1.
3. Glucose-6-phosphate to Glucose:
Catalyzed by glucose-6-phosphatase in the liver and kidneys, allowing glucose release into the bloodstream.
Significance of Gluconeogenesis
1. Fasting or Starvation:
Maintains blood glucose levels when glycogen stores are depleted.
2. Prolonged Exercise:
Sustains blood glucose as muscle glycogen depletes.
3. Low Carbohydrate Intake:
Provides glucose for the brain and red blood cells in low-carb diets.
4. Recovery from Anaerobic Exercise:
Recycles lactate into glucose via the Cori cycle.
Regulation of Gluconeogenesis
Controlled by hormones (insulin, glucagon) and allosteric regulation of key enzymes.
Ensures balance with glycolysis, maintaining energy homeostasis and preventing blood glucose imbalances.