[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Cyclooxygenase (COX-1 and COX-2)

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

# Cyclooxygenase (COX-1 and COX-2)

Cyclooxygenase turns arachidonic acid into the parent of all prostaglandins and thromboxanes. Aspirin and NSAIDs block it.

Updated 2026-11-01

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## Key facts

- Two activities in one enzyme: the cyclooxygenase adds two O₂ to arachidonic acid (→ PGG₂); the peroxidase reduces PGG₂ to PGH₂.
- PGH₂ is the common precursor of the 2-series prostaglandins, prostacyclin and thromboxane A₂.
- COX-1 (PTGS1) works all the time: stomach-protecting PGE₂, platelet thromboxane A₂.
- COX-2 (PTGS2) is induced by cytokines such as IL-1β and by bacterial lipopolysaccharide: the inflammation isoform.

**Also called**
Prostaglandin G/H synthase, Prostaglandin-endoperoxide synthase

**EC number**
[1.14.99.1](https://www.enzyme-database.org/query.php?ec=1.14.99.1)

**Genes**
PTGS1, PTGS2

**Structure (PDB)**
[5F19](https://www.rcsb.org/structure/5F19)

## Structure

- A peripheral membrane protein on the lumenal side of the endoplasmic reticulum and the nuclear envelope.
- Structure 5F19 is human COX-2 after aspirin has acetylated it.

## Regulation

- COX-1 is constitutive; COX-2 is switched on by cytokines and mitogens.
- S-nitrosylation by inducible nitric oxide synthase activates COX-2.

## Inhibitors and toxins

- Acetylsalicylic acid: acetylates a serine in the active site and switches the cyclooxygenase off for good.
- Non-selective NSAIDs such as ibuprofen: reversible inhibitors of COX-1 and COX-2.
- Celecoxib: an NSAID that prefers COX-2.

## Clinical notes

- Blocking COX lowers pain, fever and inflammation.
- Less COX-1 prostaglandin in the stomach lining raises the risk of ulcers and bleeding.
- Low-dose acetylsalicylic acid is used to prevent heart attack and stroke because it silences platelet thromboxane A₂.
- NSAIDs other than acetylsalicylic acid, celecoxib included, carry a warning about heart attack and stroke.
- Acetylated COX-2 does not simply stop: it shifts toward lipid mediators that help inflammation resolve.

## Drugs that act here

- [Acetylsalicylic acid](https://durgical.com/en/pharmacology/acetylsalicylic-acid/)
- [Ibuprofen](https://durgical.com/en/pharmacology/ibuprofen/)
- [Celecoxib](https://durgical.com/en/pharmacology/celecoxib/)
- [Paracetamol](https://durgical.com/en/pharmacology/paracetamol/)
- [Indometacin](https://durgical.com/en/pharmacology/indometacin/)
- [Diclofenac](https://durgical.com/en/pharmacology/diclofenac/)
- [Ketorolac](https://durgical.com/en/pharmacology/ketorolac/)
- [Naproxen](https://durgical.com/en/pharmacology/naproxen/)
- [Meloxicam](https://durgical.com/en/pharmacology/meloxicam/)
- [Piroxicam](https://durgical.com/en/pharmacology/piroxicam/)

## Pathways

- [Prostaglandin and thromboxane synthesis](https://durgical.com/en/biochemistry/pathways/prostaglandin-and-thromboxane-synthesis/)

## Related conditions

- [Peptic ulcer disease](https://durgical.com/en/conditions/peptic-ulcer-disease/)
- [Upper gastrointestinal bleeding](https://durgical.com/en/conditions/upper-gastrointestinal-bleeding/)
- [Rheumatoid arthritis](https://durgical.com/en/conditions/rheumatoid-arthritis/)
- [Myocardial Infarction (Heart Attack)](https://durgical.com/en/conditions/myocardial-infarction/)

## Test yourself

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

## What are the two activities of cyclooxygenase?

Cyclooxygenase (arachidonic acid + 2 O₂ → PGG₂) and peroxidase (PGG₂ → PGH₂).

## Why does acetylsalicylic acid act differently from ibuprofen on COX?

It acetylates a serine and inactivates the enzyme irreversibly; ibuprofen binds reversibly.

## Which isoform is induced in inflammation?

COX-2 (PTGS2), induced by cytokines such as IL-1β and by lipopolysaccharide.

## Why do NSAIDs raise the risk of stomach ulcers?

They cut COX-1 prostaglandins that protect the gastric lining.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/biochemistry/enzymes/cyclooxygenase/)

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

Sources: [PTGS1: Prostaglandin G/H synthase 1 (human)](https://rest.uniprot.org/uniprotkb/P23219.txt) (UniProt, 2026); [PTGS2: Prostaglandin G/H synthase 2 (human)](https://rest.uniprot.org/uniprotkb/P35354.txt) (UniProt, 2026); [EC 1.14.99.1: prostaglandin-endoperoxide synthase](https://enzyme.expasy.org/EC/1.14.99.1) (ExPASy ENZYME, SIB Swiss Institute of Bioinformatics, 2026); [5F19: The Crystal Structure of Aspirin Acetylated Human Cyclooxygenase-2](https://www.rcsb.org/structure/5F19) (RCSB Protein Data Bank, 2026); [Aspirin: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682878.html) (MedlinePlus, US National Library of Medicine, 2026); [Celecoxib: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a699022.html) (MedlinePlus, US National Library of Medicine, 2026).

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Representative model, for educational purposes only.

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