Citric Acid Cycle: The Krebs cycle, also known as the citric acid cycle or TCA cycle is a series of reactions that take place in the mitochondria resulting in oxidation of acetyl CoA to release carbon dioxide and hydrogen atoms that later lead to the formation of water.

• This cycle is termed the citric acid cycle as the first metabolic intermediate formed in the cycle is citric acid.
• This cycle is also termed tricarboxylic acid (TCA) because it was then not certain whether citric acid or some other tricarboxylic acid (g., isocitric acid) was the first product of the cycle. However, now it has been known that the first product is indeed citric acid and thus the use of this name has since been discouraged.
• This cycle only occurs under aerobic conditions as energy-rich molecules like NAD⁺ and FAD can only be retrieved from their reduced form once they transfer electrons to molecular oxygen.
• The citric acid cycle is the final common pathway for the oxidation of all biomolecules; proteins, fatty acids, carbohydrates. Molecules from other cycles and pathways enter this cycle through Acetyl CoA.
• The citric acid cycle is a cyclic sequence of reactions formed of 8 enzyme-mediated reactions.
• This cycle is also particularly important as it provides electrons/ high-energy molecules to the electron transport chain for the production of ATPs and water.
• Pyruvate formed at the end of glycolysis is first oxidized into Acetyl CoA which then enters the citric acid cycle.

Citric Acid Cycle Equation/ Reaction

The overall reaction/ equation of the citric acid cycle is:

Acetyl CoA + 3 NAD⁺ + 1 FAD + 1 ADP + 1 P_i    →   2 CO₂ + 3 NADH + 3 H⁺ + 1 FADH₂ + 1 ATP

In words, the equation is written as:

Acetyl CoA + Nicotinamide adenine dinucleotide + Flavin adenine dinucleotide + Adenosine diphosphate + Phosphate   →   Pyruvate + Water + Adenosine triphosphate + Nicotinamide adenine dinucleotide + Hydrogen ions

Citric Acid Cycle Location

• The citric acid cycle in eukaryotes takes place in the mitochondria while in prokaryotes, it takes place in the cytoplasm.
• The pyruvate formed in the cytoplasm (from glycolysis) is brought into the mitochondria where further reactions take place.
• The different enzymes involved in the citric acid cycle are located either in the inner membrane or in the matrix space of the mitochondria.

Citric Acid Cycle Steps

It is an eight-step process. Krebs cycle or TCA cycle takes place in the matrix of mitochondria under aerobic condition.

Step 1: The first step is the condensation of acetyl CoA with 4-carbon compound oxaloacetate to form 6C citrate, coenzyme A is released. The reaction is catalysed by citrate synthase.

Step 2: Citrate is converted to its isomer, isocitrate. The enzyme aconitase catalyses this reaction.

Step 3: Isocitrate undergoes dehydrogenation and decarboxylation to form 5C 𝝰-ketoglutarate. A molecular form of CO₂ is released. Isocitrate dehydrogenase catalyses the reaction. It is an NAD⁺ dependent enzyme. NAD⁺ is converted to NADH.

Step 4: 𝝰-ketoglutarate undergoes oxidative decarboxylation to form succinyl CoA, a 4C compound. The reaction is catalyzed by the 𝝰-ketoglutarate dehydrogenase enzyme complex. One molecule of CO₂ is released and NAD⁺ is converted to NADH.

Step 5: Succinyl CoA forms succinate. The enzyme succinyl CoA synthetase catalyses the reaction. This is coupled with substrate-level phosphorylation of GDP to get GTP. GTP transfers its phosphate to ADP forming ATP.

Step 6: Succinate is oxidised by the enzyme succinate dehydrogenase to fumarate. In the process, FAD is converted to FADH₂.

Step 7: Fumarate gets converted to malate by the addition of one H₂O. The enzyme catalysing this reaction is fumarase.

Step 8: Malate is dehydrogenated to form oxaloacetate, which combines with another molecule of acetyl CoA and starts the new cycle. Hydrogens removed, get transferred to NAD⁺ forming NADH. Malate dehydrogenase catalyses the reaction.

Citric Acid Cycle Products

Each citric acid cycle forms the following products:

• 2 molecules of CO₂ are released. Removal of CO₂ or decarboxylation of citric acid takes place at two places:
  1. In the conversion of isocitrate (6C) to 𝝰-ketoglutarate (5C)
  2. In the conversion of 𝝰-ketoglutarate (5C) to succinyl CoA (4C)
• 1 ATP is produced in the conversion of succinyl CoA to succinate
• 3 NAD⁺ are reduced to NADH and 1 FAD⁺ is converted to FADH₂ in the following reactions:
  1. Isocitrate to 𝝰-ketoglutarate → NADH
  2. 𝝰-ketoglutarate to succinyl CoA → NADH
  3. Succinate to fumarate → FADH₂
  4. Malate to Oxaloacetate → NADH

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By Team Learning Mantras