Citric Acid Cycle Overview

Citric Acid Cycle Overview

• The Citric Acid Cycle (CAC), also known as the Krebs cycle, is a metabolic pathway that occurs in the mitochondrial matrix.
• The CAC's primary function is to oxidize Acetyl-CoA to carbon dioxide and water, releasing energy in the process.
• The CAC generates energy by capturing electrons and transferring them to NADH and FADH2, important electron carriers that ultimately produce ATP during oxidative phosphorylation.

How the Citric Acid Cycle Begins

• Acetyl-CoA, a 2-carbon molecule produced from pyruvate in glycolysis, enters the CAC.
• Pyruvate is transported from the cytosol into the mitochondrial matrix by the mitochondrial pyruvate carrier.
• Pyruvate is converted to Acetyl-CoA by the Pyruvate Dehydrogenase Complex.
• Acetyl-CoA then combines with Oxaloacetate (4-carbon molecule) to form Citrate (6-carbon molecule).
• The reaction is catalyzed by Citrate Synthase.

Key Reactions of the Citric Acid Cycle

• Step 1: Acetyl-CoA + Oxaloacetate → Citrate (catalyzed by Citrate Synthase)
• Step 2: Citrate → Isocitrate (catalyzed by Aconitase)
• Step 3: Isocitrate → α-Ketoglutarate + CO2 (catalyzed by Isocitrate Dehydrogenase)
• Step 4: α-Ketoglutarate + CO2 → Succinyl-CoA (catalyzed by α-Ketoglutarate Dehydrogenase complex)
• Step 5: Succinyl-CoA → Succinate (catalyzed by Succinyl-CoA Synthetase)
• Step 6: Succinate → Fumarate (catalyzed by Succinate Dehydrogenase)
• Step 7: Fumarate → Malate (catalyzed by Fumarase)
• Step 8: Malate → Oxaloacetate (catalyzed by Malate Dehydrogenase)

Key Concepts for Understanding the Citric Acid Cycle

• Thioester Bond: A high-energy bond linking the acyl group to the thiol group in Acetyl-CoA, crucial for driving the cycle forward.
• Oxidative Decarboxylation: The process of losing a carbon atom in the form of CO2 during oxidation.
• Substrate Level Phosphorylation: Direct phosphorylation of ADP to ATP without the involvement of an electron transport chain, like in step 5 (Succinyl-CoA to Succinate) of the cycle.

Energy Yield of the Citric Acid Cycle

• Each turn of the Citric Acid Cycle produces:

  • 3 NADH molecules
  • 1 FADH2 molecule
  • 1 GTP molecule (energetically equivalent to ATP)

• The cycle runs twice for every glucose molecule, producing 6 NADH, 2 FADH2, and 2 ATP.

• Total ATP equivalents generated per glucose molecule from the CAC: 20

  • NADH produces 2.5 ATP equivalents per molecule, so 6 NADH = 15 ATP.
  • FADH2 produces 1.5 ATP equivalents per molecule, so 2 FADH2 = 3 ATP.
  • GTP is equivalent to 1 ATP, for a total of 2 ATP.
  • Therefore, the total ATP equivalent generated is 15 + 3 + 2 = 20 ATP

• GTP produced is energetically equivalent to ATP.

• NADH produces 2.5 ATP equivalents per molecule.

• FADH2 produces 1.5 ATP equivalents per molecule.

• The total ATP yield per glucose molecule from the CAC is 20.

Overall Energy Yield of Glucose Oxidation

• The total ATP yield per glucose molecule under aerobic conditions, including glycolysis and oxidative phosphorylation: 32.
• Glycolysis: 2 ATP (net) + 5 ATP (from NADH) = 7 ATP
• Pyruvate oxidation: 5 ATP (from NADH)
• Citric Acid Cycle: 20 ATP
• Total: 32 ATP.

Noteworthy Intermediates of the Citric Acid Cycle

• Citrate, Isocitrate, α-Ketoglutarate, Succinyl-CoA, Succinate, Fumarate, Malate, Oxaloacetate

Memory Aid for Citric Acid Cycle Intermediates

• “The CIA Sings Country Songs For Me On-Stage.”
  • The C stands for Citrate, the I for Isocitrate, the A for Alpha-Ketoglutarate.
  • Sings Country represents Succinyl-CoA (Country referring to CoA).
  • Songs refers to Succinate.
  • For refers to Fumarate.
  • Me for Malate.
    • On-Stage for Oxaloacetate.

Explore the fundamental aspects of the Citric Acid Cycle, also known as the Krebs cycle, which is vital for energy production in cellular respiration. Learn how Acetyl-CoA is transformed into citrate and the key reactions that drive this metabolic pathway in the mitochondrial matrix.