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Understanding the Krebs Cycle Mechanism

Mar 31, 2025

Lecture on the Krebs Cycle (Citric Acid Cycle)

Overview

  • The Krebs Cycle, also known as the Citric Acid Cycle or Tricarboxylic Acid Cycle, is a key metabolic pathway occurring in the mitochondrial matrix.
  • It plays a critical role in cellular respiration, allowing for ATP production by providing reduced electron carriers for the Electron Transport System (ETS).

Relationship with Electron Transport System

  • ETS requires NADH and FADH2 to function; these are supplied by the Krebs Cycle.
  • Oxygen is required for ETS and indirectly for the Krebs Cycle to function effectively.

Krebs Cycle Steps

  1. Formation of Citrate:

    • Acetyl CoA combines with oxaloacetate to form citrate.
    • Initiated by an enzyme that binds both molecules, facilitating their reaction.
  2. Isomerization to Isocitrate:

    • Citrate is converted to isocitrate by removing and reattaching water in a different configuration.
    • Enzyme involved is aconitase.
  3. Oxidation and Decarboxylation:

    • Isocitrate is oxidized to alpha-ketoglutarate, producing NADH and releasing CO2.
    • A secondary alcohol group is oxidized to a ketone.
  4. Further Oxidation:

    • Alpha-ketoglutarate is converted to succinyl-CoA, releasing another CO2 and producing NADH.
    • Succinyl-CoA is transformed into succinate, generating GTP, which can be converted to ATP.
  5. Formation of Fumarate:

    • Succinate is oxidized to fumarate, producing FADH2.
    • This step involves the creation of a carbon-carbon double bond.
  6. Hydration to Malate:

    • Fumarate is hydrated to malate by adding water.
  7. Final Oxidation:

    • Malate is oxidized to regenerate oxaloacetate, producing NADH.

Key Points

  • The cycle produces 3 NADH, 1 FADH2, 1 GTP (converted to ATP), and releases 2 CO2 per acetyl CoA.
  • No ATP is directly produced in the Krebs Cycle; ATP is generated in the ETS using NADH and FADH2.

Additional Insights

  • The cycle is crucial for energy production under aerobic conditions.
  • If components of the ETS are inhibited, this can impact ATP yield.
  • Complex metabolic control mechanisms ensure balance between cycle substrates and products.

Summary

  • Inputs: 1 Acetyl CoA, 3 NAD+, 1 FAD, 1 GDP, and inorganic phosphate.
  • Outputs: 2 CO2, 1 oxaloacetate, 3 NADH (9 ATP), 1 FADH2 (2 ATP), and 1 GTP (1 ATP equivalent).
  • Total ATP Yield from One Turn: 12 ATP from ETS.

Recommendations

  • Study the detailed steps using a blank cycle diagram.
  • Revisit lecture material and complete supplementary modules.
  • Engage in office hours for further clarification.