Outline the main stages of the Krebs cycle and state where it occurs in the cell according to GCE 2019,Q5

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The Krebs cycle, also known as the citric acid cycle or tricarboxylic acid (TCA) cycle, is a crucial metabolic pathway involved in cellular respiration. It takes place in the mitochondria of eukaryotic cells. Below are the main stages of the Krebs cycle:

  1. Formation of Citrate:

    • Acetyl-CoA (from pyruvate and fatty acid oxidation) combines with oxaloacetate to form citrate (citric acid).
  2. Isomerization:

    • Citrate is rearranged to form isocitrate through a two-step process involving the intermediate cis-aconitate.
  3. Oxidation of Isocitrate:

    • Isocitrate is oxidized to α-ketoglutarate. This reaction also reduces NAD+ to NADH and involves the release of CO2.
  4. Oxidation of α-Ketoglutarate:

    • α-Ketoglutarate undergoes further oxidation to succinyl-CoA, generating another NADH and releasing a second molecule of CO2.
  5. Conversion of Succinyl-CoA to Succinate:

    • Succinyl-CoA is converted to succinate, producing GTP (or ATP) through substrate-level phosphorylation and releasing CoA.
  6. Oxidation of Succinate:

    • Succinate is oxidized to fumarate, with the reduction of FAD to FADH2.
  7. Hydration of Fumarate:

    • Fumarate is hydrated to form malate.
  8. Oxidation of Malate:

    • Malate is oxidized back to oxaloacetate, with the reduction of NAD+ to NADH, thus completing the cycle.

The overall reaction of the Krebs cycle produces energy-rich molecules (NADH and FADH2) that are used in the electron transport chain for ATP synthesis, along with CO2 as a waste product.