[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Prostaglandin and thromboxane synthesis [Biochemistry](https://durgical.com/en/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 ## Interactive map ## 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](https://durgical.com/en/biochemistry/molecules/phosphatidylcholine/) + H₂O → [Arachidonic acid](https://durgical.com/en/biochemistry/molecules/arachidonic-acid/) + Lysophospholipid Cuts 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)](https://durgical.com/en/biochemistry/enzymes/cyclooxygenase/)** irreversible [Arachidonic acid](https://durgical.com/en/biochemistry/molecules/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 →](https://durgical.com/en/conditions/peptic-ulcer-disease/) - **Step 3 · [Peroxidase activity of COX-1/COX-2](https://durgical.com/en/biochemistry/enzymes/cyclooxygenase/)** irreversible Prostaglandin G₂ (PGG₂) → [Prostaglandin H₂](https://durgical.com/en/biochemistry/molecules/prostaglandin-h/) + H₂O At 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 →](https://durgical.com/en/conditions/asthma/) - **Step 4 · Thromboxane A synthase (TBXAS1, CYP5A1)** irreversible [Prostaglandin H₂](https://durgical.com/en/biochemistry/molecules/prostaglandin-h/) → [Thromboxane A₂](https://durgical.com/en/biochemistry/molecules/thromboxane-a/) In 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) →](https://durgical.com/en/conditions/myocardial-infarction/) ## 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 - [Prostaglandin and thromboxane synthesis](https://durgical.com/en/biochemistry/pathways/prostaglandin-and-thromboxane-synthesis/) ## Related conditions - [Myocardial Infarction (Heart Attack)](https://durgical.com/en/conditions/myocardial-infarction/) - [Peptic ulcer disease](https://durgical.com/en/conditions/peptic-ulcer-disease/) - [Asthma](https://durgical.com/en/conditions/asthma/) - [Ischaemic stroke](https://durgical.com/en/conditions/ischaemic-stroke/) ## Related - [Phosphatidylcholine (lecithin)](https://durgical.com/en/biochemistry/molecules/phosphatidylcholine/) - [Arachidonic acid](https://durgical.com/en/biochemistry/molecules/arachidonic-acid/) - [Prostaglandin H₂ (PGH₂)](https://durgical.com/en/biochemistry/molecules/prostaglandin-h/) - [Thromboxane A₂ (TXA₂)](https://durgical.com/en/biochemistry/molecules/thromboxane-a/) - [Cyclooxygenase (COX-1 and COX-2)](https://durgical.com/en/biochemistry/enzymes/cyclooxygenase/) - [Eicosanoids: prostaglandins, thromboxanes and leukotrienes](https://durgical.com/en/biochemistry/topics/eicosanoids-prostaglandins-thromboxanes-and-leukotrienes/) - [Phospholipids](https://durgical.com/en/biochemistry/topics/phospholipids/) - [Membrane structure](https://durgical.com/en/biochemistry/topics/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. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/biochemistry/pathways/prostaglandin-and-thromboxane-synthesis/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [TBXAS1 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/tbxas1/) (MedlinePlus, US National Library of Medicine, 2026); [Cytosolic phospholipase A2 (PLA2G4A) - Homo sapiens](https://www.uniprot.org/uniprotkb/P47712/entry) (UniProt, 2026); [Prostacyclin synthase (PTGIS) - Homo sapiens](https://www.uniprot.org/uniprotkb/Q16647/entry) (UniProt, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011). [← All of biochemistry](https://durgical.com/en/biochemistry/) ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/biochemistry/pathways/prostaglandin-and-thromboxane-synthesis/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/pathways/prostaglandin-and-thromboxane-synthesis/