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
- Genes
- PTGS1, PTGS2
- Structure (PDB)
- 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
- Ibuprofen
- Celecoxib
- Paracetamol
- Indometacin
- Diclofenac
- Ketorolac
- Naproxen
- Meloxicam
- Piroxicam
Pathways
Related conditions
- Peptic ulcer disease
- Upper gastrointestinal bleeding
- Rheumatoid arthritis
- Myocardial Infarction (Heart Attack)
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.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: PTGS1: Prostaglandin G/H synthase 1 (human) (UniProt, 2026); PTGS2: Prostaglandin G/H synthase 2 (human) (UniProt, 2026); EC 1.14.99.1: prostaglandin-endoperoxide synthase (ExPASy ENZYME, SIB Swiss Institute of Bioinformatics, 2026); 5F19: The Crystal Structure of Aspirin Acetylated Human Cyclooxygenase-2 (RCSB Protein Data Bank, 2026); Aspirin: MedlinePlus Drug Information (MedlinePlus, US National Library of Medicine, 2026); Celecoxib: MedlinePlus Drug Information (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.