Krebs Cycle Study Notes

Overview of the Krebs Cycle

  • Also known as the Tricarboxylic Acid Cycle (TCA Cycle) or Citric Acid Cycle.

Recap of Glycolysis

  • Glycolysis Definition: The process by which a six-carbon glucose molecule (C₆H₁₂O₆) is converted into two three-carbon molecules known as pyruvate.
  • Key Outcomes of Glycolysis:
    • Production of 2 molecules of NADH
    • Production of 2 molecules of ATP
  • Purpose of glycolysis is to extract hydrogen and electrons from glucose, setting the stage for cellular respiration.
  • Further detail in separate glycolysis video recommended.

Overview of Cellular Respiration

  • Involves three major processes:
    1. Glycolysis
    2. Krebs Cycle (Citric Acid Cycle)
    3. Electron Transport Chain
  • Main goal: Produce ATP, either directly or indirectly through NADH or FADH₂.

Transition from Glycolysis to Krebs Cycle

  • Pyruvate Conversion: The three-carbon molecule pyruvate must be transported into the mitochondria to enter the Krebs Cycle.
  • Conversion to Acetyl CoA: Pyruvate is transformed into:
    • A two-carbon molecule (acetyl) by losing one carbon in the form of carbon dioxide (CO₂).
    • A coenzyme A (CoA) is also added.
  • **Components Involved:
    • NAD⁺ is reduced to NADH + H⁺.
    • Fired enzymes include Pyruvate Dehydrogenase, which facilitates the conversion.

Role of B Vitamins

  • Thiamine Pyrophosphate (TPP): A derivative of vitamin B₁ is required for the conversion of pyruvate to acetyl CoA.
  • Pantothenic Acid (B₅): Necessary for the addition of CoA.
  • Nicotinamide Adenine Dinucleotide (NAD⁺): A derivative of vitamin B₃, necessary for hydrogen transfer in reactions.

Krebs Cycle Steps

  1. Formation of Citrate:

    • Acetyl CoA (2 carbons) combines with Oxaloacetate (4 carbons) to produce Citrate (6 carbons).
    • Enzyme involved: Citrate Synthase.

  2. Rearrangement to Isocitrate:

    • Citrate undergoes hydration and dehydration through the enzyme Aconitase to form Isocitrate.

  3. Isocitrate to Alpha-Ketoglutarate:

    • Isocitrate loses a carbon (as CO₂) and reduces NAD⁺ to NADH via Isocitrate Dehydrogenase.
    • This results in a five-carbon molecule known as Alpha-Ketoglutarate.

  4. Alpha-Ketoglutarate to Succinyl CoA:

    • Alpha-Ketoglutarate loses another carbon as CO₂ and produces NADH under the action of Alpha-Ketoglutarate Dehydrogenase, resulting in Succinyl CoA.

  5. Succinyl CoA to Succinate:

    • Succinyl CoA releases CoA, producing Succinate. This reaction can generate ATP or GTP especially through Succinyl CoA Synthetase.

  6. Succinate to Fumarate:

    • This transition involves FAD reducing to FADH₂ via Succinate Dehydrogenase.

  7. Fumarate to Malate:

    • Fumarate converts to Malate via hydration through the enzyme Fumarase.

  8. Malate to Oxaloacetate:

    • Malate is oxidized, converting NAD⁺ to NADH, leading back to Oxaloacetate through the action of Malate Dehydrogenase.

Yield from the Krebs Cycle

  • Each glucose leads to:
    • Carbon Dioxide: 4 CO₂ produced (two per acetyl CoA, 2 acetyl CoA are created from one glucose).
    • NADH: 6 NADH produced.
    • FADH₂: 2 FADH₂ produced.
    • ATP: 2 ATP generated directly.
  • Overall Importance: NADH and FADH₂ are essential for the Electron Transport Chain for further ATP production.

Interconnections with Other Molecules

  • Amino acids can feed into or be synthesized from various intermediates in the Krebs cycle (e.g., Alpha-Ketoglutarate).
  • Fatty acids can also be converted to Acetyl CoA, which enters the Krebs cycle.

Ketogenesis and Glucose Deprivation

  • In cases of low glucose (e.g., during strict dieting):
    • Oxaloacetate can be converted to glucose via gluconeogenesis, indicating its importance.
    • Without oxaloacetate, Acetyl CoA accumulates and forms ketones in the liver (Ketogenesis).
    • Ketones can shuttle between liver and brain, being utilized by the brain when glucose is low.

Conclusion

  • The Krebs cycle is integral to cellular respiration, linking various metabolic pathways and underscoring the importance of vitamins in energy metabolism throughout the cycle.