Lecture Notes on Ketone-Fueled Brain and Muscle Glycogen Metabolism

Introduction

• Focus on keto adaptation in muscle and glycogen metabolism.
• Data from a 2015 study on ultra-endurance athletes.
• Comparing elite athletes on high-carb vs. low-carb diets.

Key Findings

• Fat Oxidation:
  • Low-carb athletes: twice the fat oxidation.
  • Used ~90% fat during exercise, high-carb athletes used ~40-50%.
• Glycogen Levels:
  • Resting, post-exercise, and recovery glycogen levels were almost identical between low-carb and high-carb athletes.
  • Unexpected finding as conventional wisdom suggests high carbohydrate is needed for glycogen maintenance.

Glycogen Breakdown and Utilization

• Glycogen Utilization:
  • Rate of glycogen breakdown similar between diet groups.
  • Calculations showed 160g of glycogen depletion during exercise.
  • Only ~60g accounted for in glucose oxidation to ATP.
• Puzzling Observation:
  • Unclear what happens to the unaccounted 100g of glycogen.

Biochemical Insights

• Glycolysis and Pyruvate Fate:
  • Glycogen breaks down to glucose, then to pyruvate via glycolysis.
  • Pyruvate typically converted to Acetyl-CoA through PDH for Krebs cycle.
  • In keto diets, PDH activity decreases; fatty acids become major Acetyl-CoA source.
• Alternative Pyruvate Pathways:
  • Oxaloacetate Production:
    • Pyruvate can convert to oxaloacetate, essential for Krebs cycle.
    • Old teaching: "Fat burns in the flame of carbohydrate."
  • Lactate Formation:
    • Pyruvate conversion to lactate likely increases in keto-adapted athletes.
    • Lactate serves as a carbon source and energy.
  • Pentose Phosphate Pathway:
    • Produces reducing equivalents (NADPH) and five-carbon sugars for nucleotide synthesis.

Hypothetical and Evolutionary Perspectives

• Possible evolutionary advantages of maintaining normal glycogen levels in keto adaptability.
• Role of glucose in promoting reducing power and nucleotide synthesis.

Conclusion

• Keto adaptation presents unexpected findings in glycogen metabolism.
• Further research needed to explore the unaccounted glycogen and its implications.