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[Biochemistry](https://durgical.com/en/biochemistry/) · Enzyme

# 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](https://www.enzyme-database.org/query.php?ec=2.3.3.1)

**Genes**
CS

**Structure (PDB)**
[2CTS](https://www.rcsb.org/structure/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

- [Krebs cycle (citric acid cycle)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/)
- [Ethanol metabolism](https://durgical.com/en/biochemistry/pathways/ethanol-metabolism/)

## Related conditions

- [Fluoroacetate poisoning](https://durgical.com/en/conditions/fluoroacetate-poisoning/)

## Related

- [Acetyl-CoA](https://durgical.com/en/biochemistry/molecules/acetyl-coa/)
- [Citrate](https://durgical.com/en/biochemistry/molecules/citrate/)

## 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)](https://www.uniprot.org/uniprotkb/O75390/entry) (UniProt, 2026); [Citric acid cycle (TCA cycle)](https://reactome.org/PathwayBrowser/#/R-HSA-71403) (Reactome, 2026); [2CTS: Citrate synthase with citrate and CoA](https://www.rcsb.org/structure/2CTS) (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/biochemistry/enzymes/citrate-synthase/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/citrate-synthase/