Krebs Cycle | Zoology Optional Notes for UPSC PDF Download

Introduction and Nomenclature

• Citric Acid Cycle Definition: The citric acid cycle, also known as the Krebs cycle, is a vital metabolic pathway involving the oxidation of biomolecules (proteins, fatty acids, and carbohydrates).
• Tricarboxylic Acid (TCA): Originally named due to uncertainty about the first product (now confirmed as citric acid), the term TCA is synonymous with the Krebs cycle.

Cycle Overview

• Location:

  • In eukaryotes: Mitochondria.
  • In prokaryotes: Cytoplasm.
  • Transport: Pyruvate from glycolysis enters mitochondria for further reactions.

• Aerobic Conditions: Exclusive occurrence under aerobic conditions due to the involvement of NAD+ and FAD, which can only be regenerated with the presence of molecular oxygen.

• Integration with Biomolecules: Acts as the final common pathway for the oxidation of diverse biomolecules. Molecules from various cycles and pathways enter through Acetyl CoA.

Equation/Reaction

Overall Reaction:
Acetyl CoA + 3 NAD⁺ + 1 FAD + 1 ADP + 1 P_i → 2 CO₂ + 3 NADH + 3 H⁺ + 1 FADH₂ + 1 ATP
In Words:
Acetyl CoA + Nicotinamide adenine dinucleotide + Flavin adenine dinucleotide + Adenosine diphosphate + Phosphate   →   Pyruvate + Water + Adenosine triphosphate + Nicotinamide adenine dinucleotide + Hydrogen ions

Enzymes and Steps

Enzyme Localization:

• Eukaryotic cells: Mostly in the mitochondrial matrix, except succinate dehydrogenase and aconitase (inner mitochondrial membrane).
• Common Requirement: Nearly all enzymes require Mg2+.

Enzymes:

1. Citrate synthase
2. Aconitase
3. Isocitrate dehydrogenase
4. α-Ketoglutarate dehydrogenase
5. Succinyl-CoA synthetase
6. Succinate dehydrogenase
7. Fumarase
8. Malate dehydrogenase

Cycle Significance

• Electron and High-Energy Molecule Provider: Critical for supplying electrons and high-energy molecules to the electron transport chain.
• ATP Production: Contributes to ATP production and water formation.
• Pyruvate Oxidation: Receives pyruvate from glycolysis, which undergoes oxidation to form Acetyl CoA for entry into the cycle.

Krebs Cycle Steps

After glycolysis, aerobic organisms embark on a crucial journey through the Krebs cycle. This cycle acts as a bridge between glycolysis and the citric acid cycle, playing a pivotal role in the oxidative metabolism of pyruvate.

Oxidative Decarboxylation of Pyruvate to Acetyl CoA

Process Overview:

• Pyruvate undergoes oxidative decarboxylation, forming Acetyl CoA and CO2.
• Catalyzed by the pyruvate dehydrogenase complex.

Citric Acid Cycle Steps: An Eight-Step Odyssey

Step 1: Condensation of Acetyl CoA with Oxaloacetate
Overview:

• Formation of citric acid from oxaloacetate and acetyl CoA.
• Catalyzed by citrate synthase.

Step 2: Isomerization of Citrate into Isocitrate
Overview:

• Conversion of citrate to isocitrate through cis-aconitase.
• Catalyzed by aconitase.

Step 3: Oxidative Decarboxylations of Isocitrate
Overview:

• Isocitrate undergoes oxidative decarboxylation to form α-ketoglutarate.
• Catalyzed by isocitrate dehydrogenase.

Step 4: Oxidative Decarboxylation of α-Ketoglutarate
Overview:

• α-Ketoglutarate undergoes oxidative decarboxylation to form succinyl-CoA and CO2.
• Catalyzed by α-ketoglutarate dehydrogenase.

Step 5: Conversion of Succinyl-CoA into Succinate
Overview:

• Succinyl-CoA converts to succinate, accompanied by GTP formation.
• Catalyzed by succinyl-CoA synthetase.

Step 6: Dehydration of Succinate to Fumarate
Overview:

• Succinate undergoes dehydration to form fumarate, involving FAD.
• Catalyzed by succinate dehydrogenase.

Step 7: Hydration of Fumarate to Malate
Overview:

• Reversible hydration of fumarate to form L-malate.
• Catalyzed by fumarate hydratase.

Step 8: Dehydrogenation of L-Malate to Oxaloacetate
Overview:

• Dehydrogenation of L-malate to form oxaloacetate.
• Catalyzed by L-malate dehydrogenase.

Krebs Cycle Products

As the Krebs cycle orchestrates its rhythmic dance, the culmination of each turn yields a bountiful harvest of essential products. This cyclic process, while consuming substrates, enriches the cellular milieu with molecules vital for energy transduction and metabolic equilibrium.

Products of One Turn of the Citric Acid Cycle

In the intricate choreography of the citric acid cycle, one complete revolution bestows an array of crucial products essential for sustaining cellular vitality.

1. NADH (Nicotinamide Adenine Dinucleotide)

• Quantity:

  • Three molecules per turn.

• Formation:

  • Arises from the oxidation-reduction reactions involving isocitrate, α-ketoglutarate, and malate.
  • One NADH is formed during the oxidative decarboxylation of pyruvate to Acetyl CoA.

2. FADH2 (Flavin Adenine Dinucleotide)

• Quantity:

  • One molecule per turn.

• Formation:

  • Generated during the oxidative decarboxylation of α-ketoglutarate.

3. GTP (or ATP)

• Quantity:

  • One molecule per turn.

• Formation:

  • Synthesized during the conversion of succinyl-CoA to succinate, involving substrate-level phosphorylation.
  • GTP can subsequently transfer its terminal phosphate group to ADP, forming ATP.

4. CO₂ (Carbon Dioxide)

• Quantity:

  • Two molecules per turn.

• Formation:

  • Released during the oxidative decarboxylation reactions involving isocitrate and α-ketoglutarate.

Conclusion

The cyclic ballet of the citric acid cycle not only facilitates the continuous regeneration of oxaloacetate but also gifts the cell with a spectrum of products, each playing a distinctive role in the grand metabolic symphony. This exquisite interplay ensures the provision of energy-rich molecules and intermediates crucial for cellular function and survival.