The Krebs Cycle (Citric Acid Cycle or Tricarboxylic Acid Cycle)

Jun 23, 2024

The Krebs Cycle (Citric Acid Cycle or Tricarboxylic Acid Cycle)

Recap of Glycolysis

  • Glycolysis: Breakdown of glucose (C6H12O6) into 2 three-carbon molecules called pyruvate.
  • Products from glycolysis:
    • 2 NADH
    • 2 ATP

Overview of Cellular Respiration

  1. Glycolysis
  2. Krebs Cycle
  3. Electron Transport Chain
  • Main goal: Produce ATP (directly or indirectly via NADH or FADH2).

Transition from Glycolysis to Krebs Cycle

  • Pyruvate (3-carbon molecule) needs to enter the mitochondria for Krebs Cycle.
  • Transformation of pyruvate to acetyl-CoA (2-carbon molecule):
    • Pyruvate loses a carbon (released as CO2).
    • Addition of Coenzyme A (CoA).
    • NAD+ is reduced to NADH + H+.
    • Enzyme: Pyruvate dehydrogenase.

Importance of B Vitamins

  • Thiamine Pyrophosphate (Vitamin B1): Required for converting pyruvate to acetyl-CoA.
  • Pantothenic Acid (Vitamin B5): Needed for CoA function.
  • Niacin (Vitamin B3): Part of NAD/NADH.
  • B vitamins are critical in cellular respiration.

Steps of Krebs Cycle

  1. Formation of Citrate
    • Acetyl-CoA (2C) + Oxaloacetate (4C) → Citrate (6C)
    • Enzyme: Citrate synthase.
  2. Isomerization to Isocitrate
    • Citrate rearranges to Isocitrate (6C).
    • Enzyme: Aconitase.
  3. Formation of Alpha-Ketoglutarate
    • Isocitrate (6C) → Alpha-Ketoglutarate (5C) + CO2.
    • NAD+ is reduced to NADH + H+.
    • Enzyme: Isocitrate dehydrogenase.
  4. Formation of Succinyl-CoA
    • Alpha-Ketoglutarate (5C) → Succinyl-CoA (4C) + CO2.
    • NAD+ is reduced to NADH + H+.
    • Enzyme: Alpha-Ketoglutarate dehydrogenase.
  5. Formation of Succinate
    • Succinyl-CoA → Succinate (4C).
    • GTP (or ATP) is produced.
    • Enzyme: Succinyl-CoA synthetase.
  6. Conversion to Fumarate
    • Succinate → Fumarate (4C).
    • FAD is reduced to FADH2.
    • Enzyme: Succinate dehydrogenase.
  7. Conversion to Malate
    • Fumarate → Malate (4C).
    • Enzyme: Fumarase.
  8. Regeneration of Oxaloacetate
    • Malate → Oxaloacetate (4C).
    • NAD+ is reduced to NADH + H+.
    • Enzyme: Malate dehydrogenase.

Krebs Cycle Outputs (Per Glucose Molecule)

  • 4 CO2
  • 6 NADH
  • 2 FADH2
  • 2 ATP

Importance of Hydrogen and Electron Carriers

  • NADH and FADH2 carry hydrogen ions and electrons to the electron transport chain.
  • These carriers are essential for producing ATP.

Additional Points

  • Amino acids can feed into and out of the Krebs Cycle at various points.
  • Fatty acids can convert to acetyl-CoA and feed into the cycle.
  • During glucose deprivation (e.g., Atkins diet), oxaloacetate can convert to glucose, affecting the cycle.
  • Accumulation of acetyl-CoA without oxaloacetate leads to ketone production (ketogenesis), which the brain can use for energy.

Final Thoughts

  • The Krebs Cycle is a central pathway in cellular respiration, critical for energy production.
  • Essential to understand the role of various vitamins and enzymes involved.

Follow Dr. Mark on social media for more insights: Instagram, Twitter, and TikTok: @drmiketoadarovich

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