Citric Acid Cycle


  • Alternative Names: The pathway is interchangeably referred to as the Citric Acid cycle, the Krebs cycle, or the Tricarboxylic Acid (TCA) cycle.

  • Chemical Structure: The name Tricarboxylic Acid cycle stems from the presence of 3 carboxyl groups3\text{ carboxyl groups} on citrate (citric acid\text{citric acid}).

  • Subcellular Location: The citric acid cycle takes place within the mitochondrial matrix.

Reaction Steps of the Citric Acid Cycle

  • Step 1: Synthesis of Citrate

    • Reactants: Acetyl Coenzyme A (Acetyl CoA, a 2 carbon2\text{ carbon} compound formed after losing a molecule of CO2\text{CO}_2) and Oxaloacetate (Oxaloacetic Acid, a 4 carbon4\text{ carbon} compound).

    • Enzyme: Citrate synthase.

    • Product: Citrate (Citric Acid, a 6 carbon6\text{ carbon} compound). Citrate is the ionized form of citric acid.

  • Step 2: Isomerization to Isocitrate

    • Reactant: Citrate (6 carbons6\text{ carbons}).

    • Enzyme: Aconitase.

    • Product: Isocitrate (6 carbons6\text{ carbons}).

  • Step 3: First Oxidative Decarboxylation

    • Reactant: Isocitrate (6 carbons6\text{ carbons}).

    • Enzyme: Isocitrate dehydrogenase.

    • Product: α\alpha-Ketoglutarate (α\alpha-Ketoglutaric acid, a 5 carbon compound5\text{ carbon compound}).

    • Mechanism & Yield: Oxidative decarboxylation occurs. Whenever CO2\text{CO}_2 is released (decarboxylation), a dehydrogenation reaction simultaneously occurs (loss of hydrogen), producing 1 molecule1\text{ molecule} of NADH from NAD+\text{NAD}^+.

  • Step 4: Second Oxidative Decarboxylation

    • Reactant: α\alpha-Ketoglutarate (5 carbons5\text{ carbons}).

    • Enzyme: α\alpha-Ketoglutarate dehydrogenase.

    • Product: Succinyl Coenzyme A (Succinyl CoA, a 4 carbon compound4\text{ carbon compound}).

    • Mechanism & Yield: A second round of decarboxylation occurs with the loss of CO2\text{CO}_2 and hydrogen, reducing NAD+\text{NAD}^+ to generate another molecule of NADH.

  • Step 5: Substrate-Level Phosphorylation

    • Reactant: Succinyl CoA (4 carbons4\text{ carbons}).

    • Enzyme: Succinyl CoA synthetase.

    • Product: Succinate (4 carbons4\text{ carbons}), which lacks the Coenzyme A group.

    • Mechanism & Yield: High-energy phosphate transfer generates GTP, which converts ADP to ATP (or directly synthesizes ATP). This step represents substrate-level phosphorylation within the cycle.

  • Step 6: Oxidation of Succinate

    • Reactant: Succinate (4 carbons4\text{ carbons}).

    • Enzyme: Succinate dehydrogenase.

    • Product: Fumarate (4 carbons4\text{ carbons}).

    • Mechanism & Yield: Two hydrogen atoms are removed from succinate (dehydrogenation) to reduce FAD into 1 molecule1\text{ molecule} of FADH2\text{FADH}_2.

  • Step 7: Hydration of Fumarate

    • Reactant: Fumarate (4 carbons4\text{ carbons}).

    • Enzyme: Fumarase.

    • Product: Malate (4 carbons4\text{ carbons}).

    • Mechanism: A molecule of water (H2O\text{H}_2\text{O}) is added across the double bond of fumarate to form malate.

  • Step 8: Regeneration of Oxaloacetate

    • Reactant: Malate (4 carbons4\text{ carbons}).

    • Enzyme: Malate dehydrogenase.

    • Product: Oxaloacetate (4 carbons4\text{ carbons}).

    • Mechanism & Yield: Malate undergoes oxidation (dehydrogenation) to regenerate oxaloacetate, producing 1 molecule1\text{ molecule} of NADH from NAD+\text{NAD}^+.

Stoichiometry, Carbon Balance, and Energy Yields

  • Stoichiometry per Glucose Molecule:

    • 1 molecule of glucose1\text{ molecule of glucose} undergoes glycolysis to produce 2 molecules of pyruvate2\text{ molecules of pyruvate}.

    • 2 molecules of pyruvate2\text{ molecules of pyruvate} yield 2 molecules of Acetyl CoA2\text{ molecules of Acetyl CoA}.

    • Therefore, 1 molecule of glucose1\text{ molecule of glucose} requires 2 rounds2\text{ rounds} of the Citric Acid Cycle.

  • Yield Per Single Round of the Citric Acid Cycle:

    • CO2\text{CO}_2 released: 2 molecules2\text{ molecules}

    • NADH generated: 3 molecules3\text{ molecules}

    • FADH2\text{FADH}_2 generated: 1 molecule1\text{ molecule}

    • ATP / GTP generated: 1 molecule1\text{ molecule} (via substrate-level phosphorylation)

  • Total Yield Per Molecule of Glucose:

    • Carbon Dioxide (CO2\text{CO}_2) Output:

      • Pyruvate conversion to Acetyl CoA: 2 CO22\text{ CO}_2 (1 CO21\text{ CO}_2 per pyruvate).

      • Citric Acid Cycle (2 rounds): 4 CO24\text{ CO}_2 (2 CO22\text{ CO}_2 per turn).

      • Total CO2\text{CO}_2 produced: 2 CO2+4 CO2=6 CO22\text{ CO}_2 + 4\text{ CO}_2 = 6\text{ CO}_2

    • Electron Carriers from Citric Acid Cycle:

      • NADH: 6 NADH6\text{ NADH} (3 NADH×2 turns3\text{ NADH} \times 2\text{ turns})

      • FADH2\text{FADH}_2: 2 FADH22\text{ FADH}_2 (1 FADH2×2 turns1\text{ FADH}_2 \times 2\text{ turns})

    • Substrate-Level Phosphorylation Balance:

      • Glycolysis yield: 2 ATP2\text{ ATP}

      • Citric Acid Cycle yield: 2 ATP2\text{ ATP} (1 ATP1\text{ ATP} per turn)

      • Total substrate-level ATP generated across pathway: 4 ATP4\text{ ATP}