Gluconeogenesis

Gluconeogenesis (GNG) is a fundamental metabolic pathway that enables organisms to synthesize glucose from non-carbohydrate sources. This process is essential for maintaining blood glucose homeostasis, particularly during periods of fasting, starvation, or intense physical activity.

Key Precursors

The main substrates for gluconeogenesis include:

• Pyruvate derived from lactate
• Amino acids from protein breakdown
• Glycerol from lipid metabolism
• Propionate (in ruminants)

Regulation and Control

Gluconeogenesis is tightly regulated through several mechanisms:

Hormonal Control

• Glucagon (stimulates)
• Insulin (inhibits)
• Cortisol (enhances)

Key Regulatory Enzymes

1. Pyruvate carboxylase
2. Phosphoenolpyruvate carboxykinase (PEPCK)
3. Fructose-1,6-bisphosphatase
4. Glucose-6-phosphatase

Tissue Distribution

In mammals, gluconeogenesis primarily occurs in the:

• Liver (main site)
• Kidneys (secondary site)
• Small intestine (minor contribution)

Clinical Significance

Disruptions in gluconeogenesis can lead to various metabolic disorders:

• Hypoglycemia
• Diabetes mellitus
• Lactic acidosis

Energy Requirements

The process requires significant energy input:

• 6 ATP molecules
• 2 GTP molecules
• 2 NADH molecules

Integration with Other Pathways

Gluconeogenesis is closely integrated with several metabolic pathways:

• Glycolysis (reverse pathway)
• Citric acid cycle
• Protein catabolism
• Fatty acid metabolism

Understanding gluconeogenesis is crucial for:

• Metabolic disease management
• Sports nutrition
• Fasting physiology
• Drug development targeting metabolic disorders