outline the Krebs cycle, explaining that oxaloacetate (4C) acts as an acceptor of the 2C fragment from acetyl coenzyme A to form citrate (6C), which is converted back to oxaloacetate in a series of small steps

Respiration – The Krebs Cycle (Citric Acid Cycle)

Objective

To outline the Krebs cycle, emphasizing that oxaloacetate (4‑carbon) acts as an acceptor of the 2‑carbon fragment from acetyl‑CoA to form citrate (6‑carbon), and that citrate is regenerated to oxaloacetate through a series of enzymatic steps.

Key Molecules

• Oxaloacetate (OAA) – 4‑carbon molecule that initiates the cycle.
• Acetyl‑CoA – 2‑carbon donor derived from pyruvate decarboxylation.
• Citrate – 6‑carbon product of the condensation reaction.
• Isocitrate, α‑Ketoglutarate, Succinyl‑CoA, Succinate, Fumarate, Malate – Intermediates that lead back to OAA.
• NAD⁺, FAD, ADP (or GDP) – Electron carriers and energy‑currency molecules reduced/produced during the cycle.

Overall Reaction

The net stoichiometry for one turn of the cycle is:

\$\text{Acetyl‑CoA} + 3\ \text{NAD}^+ + \text{FAD} + \text{GDP} + \text{P}i + \text{H}2\text{O} \rightarrow 2\ \text{CO}2 + 3\ \text{NADH} + \text{FADH}2 + \text{GTP} + \text{CoA\text{-}SH}\$

Step‑by‑Step Overview

1. Condensation: Oxaloacetate (4C) combines with acetyl‑CoA (2C) to form citrate (6C).
   

   Enzyme: Citrate synthase.
   

   \$\text{Oxaloacetate} + \text{Acetyl‑CoA} \xrightarrow{\text{citrate synthase}} \text{Citrate} + \text{CoA‑SH}\$

2. Isomerisation: Citrate is rearranged to isocitrate.
   

   Enzyme: Aconitase (citrate ⇌ cis‑aconitate ⇌ isocitrate).
   

   \$\text{Citrate} \rightleftharpoons \text{Isocitrate}\$

3. First Oxidative Decarboxylation: Isocitrate is oxidised, producing NADH and releasing CO₂, yielding α‑ketoglutarate (5C).
   

   Enzyme: Isocitrate dehydrogenase.
   

   \$\text{Isocitrate} + \text{NAD}^+ \rightarrow \alpha\text{-ketoglutarate} + \text{CO}_2 + \text{NADH}\$

4. Second Oxidative Decarboxylation: α‑Ketoglutarate is oxidised, producing NADH and CO₂, forming succinyl‑CoA (4C).
   

   Enzyme: α‑Ketoglutarate dehydrogenase complex.
   

   \$\alpha\text{-ketoglutarate} + \text{NAD}^+ + \text{CoA‑SH} \rightarrow \text{Succinyl‑CoA} + \text{CO}_2 + \text{NADH}\$

5. Substrate‑Level Phosphorylation: Succinyl‑CoA is converted to succinate, generating GTP (or ATP).
   

   Enzyme: Succinyl‑CoA synthetase.
   

   \$\text{Succinyl‑CoA} + \text{GDP} + \text{P}_i \rightarrow \text{Succinate} + \text{GTP} + \text{CoA‑SH}\$

6. Oxidation: Succinate is oxidised to fumarate, reducing FAD to FADH₂.
   

   Enzyme: Succinate dehydrogenase (complex II of the electron‑transport chain).
   

   \$\text{Succinate} + \text{FAD} \rightarrow \text{Fumarate} + \text{FADH}_2\$

7. Hydration: Fumarate is hydrated to malate.
   

   Enzyme: Fumarase.
   

   \$\text{Fumarate} + \text{H}_2\text{O} \rightarrow \text{Malate}\$

8. Final Oxidation: Malate is oxidised to oxaloacetate, producing the third NADH.
   

   Enzyme: Malate dehydrogenase.
   

   \$\text{Malate} + \text{NAD}^+ \rightarrow \text{Oxaloacetate} + \text{NADH}\$

Summary Table of the Cycle

Key Points to Remember

• Oxaloacetate is regenerated each turn, allowing the cycle to continue indefinitely as long as acetyl‑CoA is supplied.
• Each acetyl‑CoA yields 3 NADH, 1 FADH₂ and 1 GTP – the reduced cofactors feed the electron‑transport chain to produce the bulk of ATP.
• The cycle occurs in the mitochondrial matrix of eukaryotic cells and in the cytosol of many prokaryotes.