Biochemistry · Metabolic pathway
Prostaglandin and thromboxane synthesis !
Cells free arachidonic acid from membranes and turn it into prostaglandins and thromboxane, local signals for pain, fever, clotting and the stomach.
Updated 2026-11-01
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Key facts
- Phospholipase A₂ releases arachidonic acid; glucocorticoids reduce its activity (through annexin A1) and also lower COX-2.
- COX has two activities in one protein: the cyclooxygenase makes PGG₂ and the peroxidase reduces it to PGH₂, the shared precursor.
- Aspirin acetylates COX irreversibly; platelets have no nucleus, so their thromboxane stays low for their whole lifespan (about 7–10 days).
- Platelets make TXA₂ (aggregation, vasoconstriction); endothelium makes PGI₂ (blocks aggregation, dilates vessels).
- COX-1 is always present (stomach, platelets, kidney); COX-2 is induced by inflammation.
- Also called
- Cyclooxygenase pathway of eicosanoids
Regulation
- Ca²⁺ moves cPLA₂ to the membrane, and phosphorylation by MAP kinase activates it.
- Cytokines and growth factors induce COX-2; glucocorticoids repress it.
- Which prostanoid is made depends on the terminal synthase each cell type has.
The steps, one by one
- Step 1 · Cytosolic phospholipase A₂ (cPLA₂α, PLA2G4A) irreversible Phosphatidylcholine + H₂O → Arachidonic acid + LysophospholipidCuts the fatty acid at position sn-2 of membrane phospholipids, which is usually arachidonic acid.If it fails: Inherited cPLA₂α deficiency is rare: small-bowel ulcers and weak platelet function from too few eicosanoids.
- Step 2 · Cyclooxygenase activity of COX-1/COX-2 (PTGS1/PTGS2) irreversible Arachidonic acid + o2 → Prostaglandin G₂ (PGG₂)Adds two O₂ molecules to arachidonic acid, closing a five-carbon ring to make the endoperoxide PGG₂; the lipoxygenase branch competes for the same arachidonic acid (5-LOX with FLAP → 5-HPETE → LTA₄ → LTB₄ and LTC₄/D₄/E₄; zileuton blocks 5-LOX and montelukast the CysLT1 receptor).If it fails: NSAIDs block this step: fewer protective prostaglandins in the stomach (peptic ulcer) and, with aspirin, less platelet thromboxane. Peptic ulcer disease →
- Step 3 · Peroxidase activity of COX-1/COX-2 irreversible Prostaglandin G₂ (PGG₂) → Prostaglandin H₂ + H₂OAt a separate heme site of the same enzyme the hydroperoxide of PGG₂ is reduced to an alcohol, giving PGH₂, the precursor of all prostanoids.If it fails: Aspirin-exacerbated respiratory disease: with COX blocked, arachidonic acid is pushed toward leukotrienes, triggering asthma and nasal polyps. Asthma →
- Step 4 · Thromboxane A synthase (TBXAS1, CYP5A1) irreversible Prostaglandin H₂ → Thromboxane A₂In platelets this P450-family enzyme rearranges PGH₂ into thromboxane A₂, which clumps platelets and narrows vessels; in endothelium prostacyclin synthase (PTGIS) turns the same PGH₂ into PGI₂, which does the opposite, and other synthases make PGE₂, PGD₂ and PGF₂α.If it fails: Aspirin keeps platelet TXA₂ low for the platelet's whole life, which is why it prevents heart attacks; TBXAS1 deficiency causes Ghosal hematodiaphyseal dysplasia (thick bones and anaemia). Myocardial Infarction (Heart Attack) →
Clinical notes
- Low-dose aspirin prevents myocardial infarction and stroke by blocking platelet TXA₂.
- NSAIDs cause peptic ulcers by removing the protective prostaglandins (PGE₂, PGI₂) of the gastric lining.
- Aspirin-exacerbated respiratory disease: blocking COX shifts arachidonic acid to leukotrienes and triggers asthma attacks.
- Selective COX-2 inhibitors spare the stomach but raise cardiovascular risk, because they lower PGI₂ without lowering platelet TXA₂.
Pathways
Related conditions
Related
- Phosphatidylcholine (lecithin)
- Arachidonic acid
- Prostaglandin H₂ (PGH₂)
- Thromboxane A₂ (TXA₂)
- Cyclooxygenase (COX-1 and COX-2)
- Eicosanoids: prostaglandins, thromboxanes and leukotrienes
- Phospholipids
- Membrane structure
Test yourself
Think of the answer, then tap the question to see it.
Which enzyme releases arachidonic acid from membrane phospholipids?
Phospholipase A₂ (cytosolic cPLA₂α), activated by Ca²⁺; glucocorticoids reduce its activity.
Why does a single dose of aspirin affect platelets for days?
It acetylates COX irreversibly, and platelets have no nucleus to make new enzyme, so TXA₂ stays low until new platelets appear.
What opposite effects do TXA₂ and PGI₂ have?
TXA₂ from platelets causes aggregation and vasoconstriction; PGI₂ from endothelium blocks aggregation and dilates vessels.
Why can NSAIDs trigger asthma in some patients?
Blocking COX pushes arachidonic acid into the 5-lipoxygenase branch, increasing bronchoconstricting cysteinyl leukotrienes.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: TBXAS1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Cytosolic phospholipase A2 (PLA2G4A) - Homo sapiens (UniProt, 2026); Prostacyclin synthase (PTGIS) - Homo sapiens (UniProt, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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Representative model, for educational purposes only.