Citric Acid Cycle: Key Steps and Mechanisms

Citric Acid Cycle

Overview

The Citric Acid Cycle (also known as the Krebs Cycle or TCA Cycle) is a central metabolic pathway in aerobic organisms. It is responsible for the oxidation of acetyl-CoA to carbon dioxide and the generation of high-energy electron carriers (NADH, FADH2) for ATP production.

Step 1: Citrate Synthase Reaction

• Reaction: Acetyl-CoA + Oxaloacetate + H2O → Citrate + CoA-SH

• ΔG°': -32.2 kJ/mol (highly exergonic)

• Enzyme: Citrate synthase

• Key Points:

  • Water is consumed in the reaction.

  • Coenzyme A (CoA) is released.

  • This step is highly regulated and commits the acetyl group to the cycle.

• Example: The condensation of acetyl-CoA and oxaloacetate forms citrate, a six-carbon compound.

Step 2: Aconitase Reaction

• Reaction: Citrate → cis-Aconitate (intermediate) → Isocitrate

• ΔG°': +13.3 kJ/mol (endergonic)

• Enzyme: Aconitase

• Key Points:

  • Isomerization of citrate to isocitrate via cis-aconitate intermediate.

  • Involves removal and addition of water (dehydration and rehydration).

  • Citrate is a poor substrate for oxidation; isocitrate is a better substrate due to its structure.

  • This step prepares the molecule for subsequent oxidative decarboxylation.

• Example: The conversion of citrate to isocitrate allows the cycle to proceed with further oxidation steps.

Step 3: Isocitrate Dehydrogenase Reaction

• Reaction: Isocitrate + NAD+ → α-Ketoglutarate + CO2 + NADH + H+

• ΔG°': -8.4 kJ/mol (exergonic)

• Enzyme: Isocitrate dehydrogenase

• Key Points:

  • First oxidative decarboxylation in the cycle.

  • NAD+ is reduced to NADH, capturing high-energy electrons.

  • CO2 is released as a waste product.

  • This step is highly regulated and rate-limiting for the cycle.

• Example: The conversion of isocitrate to α-ketoglutarate is a key step in energy production and carbon flow.

Key Equations

• $\text{Acetyl-CoA} + \text{Oxaloacetate} + H_2O \rightarrow \text{Citrate} + \text{CoA-SH}$

• $\text{Citrate} \rightarrow \text{cis-Aconitate} \rightarrow \text{Isocitrate}$

• $\text{Isocitrate} + \text{NAD}^+ \rightarrow \alpha\text{-Ketoglutarate} + \text{CO}_2 + \text{NADH} + H^+$

Additional info:

• Each turn of the citric acid cycle generates three NADH, one FADH2, and one GTP (or ATP), along with two CO2 molecules.

• NADH and FADH2 produced are used in the electron transport chain to generate ATP.