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Understanding HIF and Metabolic Processes

May 10, 2025

Lecture Notes on Hypoxia Inducible Factor and Metabolic Pathways

Hypoxia Inducible Factor (HIF)

  • Direct oxygen sensor in cells.
  • Protein that binds with oxygen, leading to its degradation.
  • Low oxygen (5% or below) causes HIF to accumulate, moving to the nucleus.
  • Acts as a transcription factor to produce proteins for cell regulation.
  • Can stimulate angiogenesis (formation of new blood vessels) for better oxygen supply.

Endurance Training

  • Lactate Threshold Training: Important for endurance, but overtraining can lead to adverse effects like reduced mitochondria and decreased blood vessel formation.
  • Proper training balance is crucial to avoid switching cells to anabolic mode, leading to poor results.

Nobel Prize Relevance

  • Importance of HIF in cancer metastasis and metabolic reprogramming.
  • Direct oxygen sensing is more sensitive than NAD+/NADH levels.

Metabolic Pathways and Electron Transport

  • Oxygen availability determines the transition from pyruvate to acetyl-CoA.
  • Electron Carriers:
    • Glycolysis: 2 NADH per glucose.
    • Transition Step: 2 NADH per glucose.
    • Krebs Cycle: 6 NADH, 2 FADH2.
  • Electron carriers contribute to ATP synthesis by transporting electrons, pumping protons across mitochondrial membrane.

ATP Synthesis and Electron Transport Chain (ETC)

  • ATP Synthase: Uses proton gradient to produce ATP from ADP and inorganic phosphate.
  • Oxygen is the final electron acceptor, forming water not carbon dioxide.
  • FADH2 contributes less to ATP because it pumps fewer protons.
  • ATP synthase and ETC are separate but work together.

Metabolism of Glucose and Lipids

  • Glycolysis and Glycogen Storage: Glucose converted to glucose-6-phosphate, stored as glycogen (especially in liver and skeletal muscle).
  • Glycogen Loading: Used by bodybuilders to increase muscle size temporarily.
  • Excess Nutrients: Converted to fat when storage in liver and muscle is maxed out.

Fructose and Metabolic Health

  • High fructose intake linked to adipose tissue formation due to unregulated entry into cells.
  • Concerns with high fructose corn syrup in diet.

Hormonal Regulation

  • Leptin: Released by adipocytes, signals satiety, influences metabolic rate, and can affect appetite and fat storage.

Note: The presentation integrated molecular biology, physiology, and metabolism, emphasizing the balance between different metabolic pathways and their physiological implications.

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