Citric acid cycle- Pathway, energetics and significance

• The Citric Acid Cycle, also known as the Krebs cycle or the Tricarboxylic Acid (TCA) cycle, is a cornerstone of cellular metabolism, pivotal in the breakdown and conversion of carbohydrates, fats, and proteins into usable energy.
• This cycle takes place in the mitochondrial matrix of eukaryotic cells, where it serves the dual purpose of generating high-energy molecules (ATP, NADH, and FADH2) and facilitating carbon dioxide excretion as a byproduct.

Citric Acid Cycle or Krebs cycle Pathway

• Overview of the Krebs Cycle Steps

1. Formation of Citrate:

   • Enzyme: Citrate synthase
   • Process: Acetyl CoA (2 carbons) combines with oxaloacetate (4 carbons) to form citrate (6 carbons), releasing CoA.

2. Isomerization to Isocitrate:

   • Enzyme: Aconitase
   • Process: Citrate is rearranged into isocitrate via cis-aconitate as an intermediate.

3. Oxidation and Decarboxylation to α-Ketoglutarate:

   • Enzyme: Isocitrate dehydrogenase
   • Process: Isocitrate is oxidized to oxalosuccinate (6 carbons), then decarboxylated to α-ketoglutarate (5 carbons), producing NADH and releasing CO2.

4. Further Oxidation and Decarboxylation:

   • Enzyme: α-Ketoglutarate dehydrogenase complex
   • Process: α-Ketoglutarate is further oxidized and decarboxylated to form succinyl CoA (4 carbons), generating another NADH and releasing a second CO2 molecule.

5. Conversion to Succinate of Citric acid cycle:

   • Enzyme: Succinyl-CoA synthetase
   • Process: Succinyl CoA is converted into succinate, producing one molecule of GTP (or ATP).

6. Oxidation of Succinate:

   • Enzyme: Succinate dehydrogenase
   • Process: Succinate is oxidized to fumarate, reducing FAD to FADH2.

7. Hydration to Malate:

   • Enzyme: Fumarase
   • Process: Fumarate is hydrated to form malate.

8. Oxidation to Oxaloacetate:

   • Enzyme: Malate dehydrogenase
   • Process: Malate is oxidized back to oxaloacetate, reducing NAD+ to NADH and preparing the cycle to begin anew.

Products of the Krebs Cycle per Acetyl CoA

1. 3 NADH molecules: For use in the electron transport chain.
2. 1 FADH2 molecule: Also, for use in the electron transport chain.
3. 1 ATP (or GTP) molecule: Directly usable energy.
4. 2 CO2 molecules: Waste products released.

Energetics of the Citric Acid Cycle

• 3 NADH → ~7.5 ATP (via oxidative phosphorylation)
• 1 FADH2 → ~1.5 ATP
• 1 GTP (or ATP) directly produced Each cycle generates around 10 ATP equivalents.

Significance of the Citric Acid Cycle

• Energy Production: Major source of ATP, NADH, and FADH2, essential for cellular energy.
• Anaplerotic Reactions: Intermediates are precursors for biomolecules like amino acids and nucleotides.
• Metabolic Integration: Links the metabolism of carbohydrates, fats, and proteins via Acetyl CoA.
• Regulation: Enzymes in the cycle are tightly regulated based on the cell’s energy needs.
• This simplified overview highlights the Citric Acid Cycle’s critical role in energy production and metabolic regulation.

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