Lecture Notes: The Citric Acid Cycle

Introduction to Metabolic Pathways

• Glycolysis

  • Anaerobic process: does not require oxygen.
  • Allows simple organisms to generate energy by producing 2 ATP per glucose molecule.

• Evolution of Aerobic Respiration

  • Higher organisms needed more energy for activities like running, jumping, swimming.
  • Development of additional metabolic pathways was facilitated by the presence of oxygen.
  • Oxygen in the atmosphere was increased by photosynthesis from plants.

Mitochondria and Energy Production

• Role of Mitochondria
  • Location of the citric acid cycle.
  • Eukaryotic organelles that may have been separate organisms (endosymbiotic theory).

From Glycolysis to Citric Acid Cycle

• Pyruvate Processing
  • Pyruvate molecules from glycolysis enter the mitochondrial matrix.
  • In presence of NAD+, pyruvate undergoes:
    • Decarboxylation.
    • Oxidation by NAD+.
    • Attachment to Coenzyme A to form acetyl CoA.

The Citric Acid Cycle (Krebs Cycle)

• Overview

  • Also known as the tricarboxylic acid cycle.
  • Eight-step pathway involving eight enzymes.

• Steps of the Citric Acid Cycle

  1. Formation of Citrate
     • Enzyme: Citrate synthase.
     • Process: Acetyl group from acetyl CoA joins with oxaloacetate.
  2. Isomerization to Isocitrate
     • Enzyme: Aconitase.
     • Process: Removal and addition of water molecule.
  3. Oxidation to Alpha-Ketoglutarate
     • Enzyme: Isocitrate dehydrogenase.
     • Process: Oxidation by NAD+ and decarboxylation.
  4. Formation of Succinyl-CoA
     • Enzyme: Ketoglutarate dehydrogenase.
     • Process: Further oxidation and CO2 loss, joining with Coenzyme A.
  5. Formation of Succinate
     • Enzyme: Succinyl-CoA synthetase.
     • Process: Phosphate group displaces CoA, generating GTP.
  6. Oxidation to Fumarate
     • Enzyme: Succinate dehydrogenase.
     • Process: Oxidation by FAD, resulting in FADH2.
  7. Formation of Malate
     • Enzyme: Fumarase.
     • Process: Hydration.
  8. Regeneration of Oxaloacetate
     • Enzyme: Malate dehydrogenase.
     • Process: Oxidation by NAD+.

• Products per Acetyl CoA

  • 3 NADH
  • 1 FADH2
  • 1 ATP

• Products per Glucose

  • 6 NADH
  • 2 FADH2
  • 2 ATP

Significance

• Energy Payoff
  • Products move on to oxidative phosphorylation.
  • Oxidative phosphorylation generates most of the ATP in aerobic respiration.

Conclusion

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