# Eicosanoid Biochemistry > Eicosanoid biochemistry in MBBS Biochemistry: arachidonic acid release, COX and LOX pathways, thromboxane, prostacyclin and leukotrienes. - Canonical URL: https://prepelephant.com/topics/mbbs/biochemistry/eicosanoid-biochemistry - Exam / course: MBBS · Subject: Biochemistry - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Eicosanoid Biochemistry", PrepElephant, https://prepelephant.com/topics/mbbs/biochemistry/eicosanoid-biochemistry ## Direct answer Twenty-carbon arachidonic acid, released from membrane phospholipid sn-2 positions by phospholipase A2, feeds three oxygenating pathways: constitutive and inducible cyclooxygenases (COX-1 and COX-2) that make prostaglandins, prostacyclin and thromboxane; 5-lipoxygenase that makes leukotrienes; and cytochrome P450 epoxygenases making epoxyeicosatrienoic acids. Eicosanoids are local, short-lived hormones (eicosa is Greek for twenty) acting on G-protein-coupled receptors at or near their site of synthesis. The examinable pharmacology falls straight out of the chemistry: aspirin irreversibly acetylates both COX isoforms; thromboxane A2 constricts and aggregates platelets while endothelial prostacyclin opposes it; and the cysteinyl leukotrienes are the slow-reacting substance of anaphylaxis, central to asthma. ## What you must remember - **Precursor chemistry:** arachidonic acid is 5,8,11,14-eicosatetraenoic acid (omega-6), stored in membrane phosphatidylinositol and choline phospholipids; liberated by phospholipase A2, itself activated by G-protein-coupled receptor calcium signals. - **Rate-limiting and drug target:** cyclooxygenase (prostaglandin endoperoxide synthase) converts arachidonate to PGH2 through a cyclooxygenase and a peroxidase activity on the same protein; aspirin acetylates serine-530 irreversibly, non-selective NSAIDs compete reversibly. - **Platelet-endothelium balance:** platelet thromboxane A2 (COX-1) promotes aggregation and vasoconstriction with a half-life of about 30 seconds; endothelial prostacyclin (PGI2, mainly COX-2) raises cyclic AMP and prevents aggregation — low-dose aspirin tips the balance by acetylating anucleate platelets for their lifetime. - **Leukotriene arm:** 5-lipoxygenase with FLAP makes leukotriene A4; LTB4 is a potent neutrophil chemotaxin; LTC4, LTD4 and LTE4 compose the slow-reacting substance of anaphylaxis, bronchoconstrictors a thousand times stronger than histamine; zileuton inhibits the enzyme, montelukast blocks the CysLT1 receptor. - **COX-2 selectivity:** induced at inflammatory sites by cytokines and inhibited relatively selectively by celecoxib (and formerly rofecoxib), trading gastrointestinal toxicity for thrombotic risk — the mechanistic story behind rofecoxib's withdrawal. - **Numbered shorthand:** prostaglandin series 2 derives from arachidonate (two double bonds retained); series 1 from dihomo-gamma-linolenic acid; series 3 from eicosapentaenoic acid of fish oil, basis of omega-3 supplementation shifting eicosanoid balance. - **Non-steroidal side-effect logic:** gastric cytoprotective prostaglandins (PGE2, COX-1) and renal vasodilator prostaglandins explain NSAID dyspepsia, ulceration and analgesic nephropathy; misoprostol is a PGE1 analogue given as gastric protection. ## How to work through an aspirin-pharmacology case A man with a coronary stent on low-dose aspirin develops arthritic knee pain and starts a conventional NSAID; his cardiologist objects. Reason from enzyme kinetics: low-dose aspirin (75-150 milligrams) exploits the portal exposure of the anucleate platelet — with no nucleus it cannot resynthesise the acetylated enzyme for its 7-10 day lifespan, so thromboxane generation stays suppressed while endothelial cells, which retain nuclei, regenerate COX and keep making prostacyclin. A reversible non-selective NSAID taken regularly competes for the same active channel and can blunt the antiplatelet effect; COX-2-selective agents spare platelets but remove prostacyclin, tilting the balance the other way, the vascular risk that ended rofecoxib. Now the asthma mirror: a patient with aspirin-exacerbated respiratory disease worsens on NSAIDs because blocking the COX arm diverts arachidonate through 5-lipoxygenase, flooding cysteinyl leukotrienes that were already driving nasal polyposis and bronchospasm. Leukotriene receptor antagonists like montelukast are the rational add-on, a daily Indian outpatient prescription. The unifying principle: one substrate, two major enzymatic funnels, and drugs that redirect rather than delete. ## Where students slip Students call prostaglandins hormones carried in blood; they are autacoids, inactivated by 15-hydroxyprostaglandin dehydrogenase during a single pulmonary passage, which is why they act locally and are not measured as circulating hormones. The second slip is labelling COX-2 purely "the inflammatory isoform" — it is constitutive in endothelium and kidney, which is exactly why selective inhibitors raised blood pressure and thrombosis. Third, thromboxane synthase lives in platelets and prostacyclin synthase in endothelium; when a question asks why aspirin benefits coronary disease, the asymmetry of the nucleus (platelets lack one) is the answer expected. ## Frequently asked questions ### What releases arachidonic acid from membrane phospholipids? Phospholipase A2, activated by receptor-driven calcium signals and inhibited indirectly by glucocorticoid-induced lipocortin. ### How does low-dose aspirin achieve its antiplatelet effect? Irreversible acetylation of platelet COX-1 abolishes thromboxane A2 synthesis for the platelet's lifetime, while nucleated endothelium regenerates prostacyclin capacity. ### Which eicosanoids constitute slow-reacting substance of anaphylaxis? LTC4, LTD4 and LTE4, the cysteinyl leukotrienes from the 5-lipoxygenase pathway; they bronchoconstrict powerfully and are targeted by montelukast and zileuton. ### Why do COX-2 selective inhibitors carry cardiovascular risk? They spare platelet thromboxane production while suppressing endothelial prostacyclin, shifting the haemostatic balance toward aggregation. ### Which prostaglandin protects the gastric mucosa? PGE2 maintains mucus and bicarbonate secretion and mucosal blood flow through COX-1; its loss explains NSAID gastropathy and is the rationale for misoprostol.