- Gluconeogenesis is a crucial metabolic pathway that synthesizes glucose from non-carbohydrate sources, maintaining stable blood glucose levels during fasting, prolonged exercise, or low carbohydrate intake.
- It occurs mainly in the liver and kidneys.
Gluconeogenesis Pathway
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- Gluconeogenesis reverses most steps of glycolysis, except for three key steps where it uses unique enzymes:
-
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.
-
Fructose-1,6-bisphosphate to Fructose-6-phosphate:
- Catalyzed by fructose-1,6-bisphosphatase, bypassing glycolytic enzyme PFK-1.
-
Glucose-6-phosphate to Glucose:
- Catalyzed by glucose-6-phosphatase in the liver and kidneys, allowing glucose release into the bloodstream.
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Significance of Gluconeogenesis
-
Fasting or Starvation:
- Maintains blood glucose levels when glycogen stores are depleted.
-
Prolonged Exercise:
- Sustains blood glucose as muscle glycogen depletes.
-
Low Carbohydrate Intake:
- Provides glucose for the brain and red blood cells in low-carb diets.
-
Anaerobic Exercise Recovery:
- 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.
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