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Citrate synthase !

Citrate synthase opens each turn of the Krebs cycle: it joins acetyl-CoA to oxaloacetate to make citrate.

Updated 2026-10-31

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Key facts

  • Acetyl-CoA + oxaloacetate + H₂O → citrate + CoA; strongly favoured (thioester hydrolysis drives it).
  • A textbook case of induced fit: oxaloacetate closes the enzyme and creates the site for acetyl-CoA.
  • Its activity is used as a marker of a tissue's mitochondrial content.
EC number
2.3.3.1
Genes
CS
Structure (PDB)
2CTS

Regulation

  • Citrate, succinyl-CoA, NADH and ATP inhibit it; oxaloacetate supply limits it.

Inhibitors and toxins

  • Fluoroacetyl-CoA: a false substrate that yields fluorocitrate

Clinical notes

  • In fluoroacetate poisoning (the '1080' rodenticide), citrate synthase makes the real poison, fluorocitrate: 'lethal synthesis'.

Pathways

Test yourself

Think of the answer, then tap the question to see it.

Which substrate binds citrate synthase first?

Oxaloacetate; its binding closes the enzyme and forms the acetyl-CoA site.

What is 'lethal synthesis'?

Citrate synthase turns fluoroacetate into fluorocitrate, which blocks aconitase.

Which metabolites inhibit citrate synthase?

Citrate, succinyl-CoA, NADH and ATP.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: CS: Citrate synthase, mitochondrial (human) (UniProt, 2026); Citric acid cycle (TCA cycle) (Reactome, 2026); 2CTS: Citrate synthase with citrate and CoA (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.