Lecture Notes on Gluconeogenesis

Overview of Gluconeogenesis

• Gluconeogenesis: creation of new glucose
• Glycolysis: breakdown of glucose to pyruvate
• Gluconeogenesis: essentially the reverse of glycolysis
• Purpose: To produce glucose during fasting

Unique Reactions in Gluconeogenesis

Roadblock 1: Pyruvate to Phosphoenolpyruvate

• Issue: Cannot use pyruvate kinase to reverse this reaction.
• Solution: Uses different enzymes and pathway.
  • Step 1: Pyruvate → Oxaloacetate (OAA)
    • Enzyme: Pyruvate carboxylase
    • Oxaloacetate is a 4-carbon molecule; pyruvate is a 3-carbon molecule
    • Involves addition of carbon via carboxy group
  • Step 2: Oxaloacetate → Phosphoenolpyruvate (PEP)
    • Enzyme: PEP carboxykinase
    • Involves phosphorylation and energy from ATP and GTP

Roadblock 2: Conversion of Fructose-1,6-bisphosphate to Fructose-6-phosphate

• Normally, Phosphofructokinase is used in glycolysis
• Gluconeogenesis uses: Fructose-1,6-bisphosphatase (a phosphatase, removes phosphate group)
• Enzyme switching encompasses a larger change in pathway, not just enzyme.
• In glycolysis: ATP hydrolyzed to ADP (absent in gluconeogenesis)

Roadblock 3: Glucose-6-phosphate to Glucose

• Normally, hexokinase is used in glycolysis
• Gluconeogenesis uses: Glucose-6-phosphatase (removes phosphate group)

Important Notes

• Enzyme Deficiencies:
  • Lack of Glucose-6-phosphatase prevents production of glucose
  • Affects both gluconeogenesis and glycogen breakdown
  • Leads to severe hypoglycemia, life-threatening condition

Key Takeaways

• Understand the three irreversible steps in gluconeogenesis and their corresponding unique pathways.
• Important to grasp the concept rather than memorize all enzyme and molecule names.