Gluconeogenesis Lecture Notes

Introduction to Gluconeogenesis

• Definition: Synthesis of glucose from non-carbohydrate sources.
  • "Gluco" = glucose
  • "Neo" = new
  • "Genesis" = production
• Typical glucose production: Carbohydrates are broken down into glucose by enzymes.
• Special circumstances: Substances like fat, amino acids, and pyruvate are converted into glucose.

Blood Glucose Regulation

• Average blood glucose levels: 100 to 200 mg/dL throughout the day.
• Excess glucose is stored as glycogen in the liver.
• During fasting:
  • Blood glucose levels fall.
  • Glycogen (~100g) is converted back to glucose.
  • When glycogen is depleted, gluconeogenesis maintains glucose levels.
• Essential tissues: Nervous tissue and red blood cells require glucose.

Locations of Gluconeogenesis

• Occurs mainly in:
  • Liver (50-60%)
  • Kidneys (40%)
  • Minor activity in intestines

Metabolic Reactions Involved

• Glycolysis and Krebs cycle are key processes.
• Important to understand these processes in detail.

Overview of Glycolysis

• Glucose is a 6-carbon compound, converted to two 3-carbon pyruvate molecules.
• Consists of 10 reactions, with 3 being irreversible.
• Irreversible reactions regulated by specific enzymes in response to glucose concentration.

Reversal of Irreversible Reactions

• Specific enzymes upregulated during glucose deficiency (e.g., fasting) to reverse these reactions.
• Pathways:
  • Pyruvate to glucose
  • Propionate to glucose through Krebs cycle intermediates
  • Lactate to glucose

Detailed Steps in Gluconeogenesis

1. Pyruvate to Phosphoenolpyruvate
   • Pyruvate transported to mitochondria.
   • Converted to oxaloacetate by pyruvate carboxylase (CO2 and ATP used).
   • Oxaloacetate to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase (GTP used).
2. Fructose 1,6-bisphosphate to Fructose 6-phosphate
   • Catalyzed by fructose 1,6-bisphosphatase.
3. Glucose 6-phosphate back to Glucose
   • Catalyzed by glucose-6-phosphatase.

Alternate Pathways

• Propionate:
  • Converted to succinyl-CoA (Krebs cycle intermediate), then oxaloacetate.
• Lactate:
  • Directly converted to pyruvate by lactate dehydrogenase.
• Glycerol:
  • Converted to glycerol 3-phosphate then dihydroxyacetone phosphate.
  • Enters glycolysis pathway to become fructose 1,6-bisphosphate.

Conclusion

• Gluconeogenesis is crucial during fasting and low carbohydrate intake to maintain blood glucose levels.
• Understanding glycolysis and the Krebs cycle is vital for comprehending gluconeogenic pathways.

Note: For more detailed study, watch videos on glycolysis and Krebs cycle and engage with educational platforms for additional resources.