Step by Step
AA
Arachidonic acid — the precursor
Eicosanoids are derived from 20-carbon polyunsaturated fatty acids, primarily arachidonic acid (AA, 20:4 ω-6). AA is released from membrane phospholipids by phospholipase A₂ (activated by inflammation, injury, or hormones). AA then enters two major pathways: cyclooxygenase (COX) or lipoxygenase (LOX).
Memory trick: AA = the ammunition. PLA₂ = pulls the trigger. COX and LOX = two cannons.
COX
COX pathway → prostaglandins and thromboxanes
Cyclooxygenase (COX-1 and COX-2) converts AA into prostaglandin H₂ (PGH₂) — the precursor for all prostaglandins and thromboxanes. Prostaglandins: mediate inflammation, pain, fever, vasodilation. Thromboxane A₂ (TXA₂): produced by platelets — promotes platelet aggregation and vasoconstriction. NSAIDs (aspirin, ibuprofen) inhibit COX.
LOX
LOX pathway → leukotrienes
Lipoxygenase (LOX) converts AA into leukotrienes. Leukotrienes are powerful mediators of inflammation and allergy: LTB₄ attracts neutrophils. LTC₄, LTD₄, LTE₄ cause bronchoconstriction and mucus secretion — key mediators in asthma. Leukotriene antagonists (montelukast) treat asthma.
Memory trick: Leukotrienes = Leukotriene → Lungs (asthma). LOX = Locks up the lungs.
NSAID
NSAIDs — mechanism of action
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX-1 and/or COX-2, blocking prostaglandin synthesis. Aspirin: irreversible COX inhibitor (acetylates serine). Ibuprofen/naproxen: reversible COX inhibitors. COX-2 selective inhibitors (celecoxib): less GI side effects (spare COX-1 in stomach). Corticosteroids inhibit PLA₂ — blocking all eicosanoid synthesis upstream.
Applied Walkthrough
1
Tissue injury activates phospholipase A₂ → releases arachidonic acid from membrane phospholipids.
2
COX converts AA → PGH₂ → prostaglandins (pain, inflammation, fever) and TXA₂ (platelet aggregation).
3
LOX converts AA → leukotrienes (bronchoconstriction in asthma, neutrophil recruitment in infection).
4
Aspirin acetylates COX irreversibly → blocks TXA₂ in platelets permanently (antiplatelet effect lasts 10 days). Ibuprofen reversibly inhibits COX → anti-inflammatory, antipyretic, analgesic.
Exam Application
Exams test the arachidonic acid cascade, COX vs LOX pathways and their products, NSAIDs as COX inhibitors, and leukotrienes as asthma mediators. Know aspirin's irreversible mechanism vs NSAIDs' reversible inhibition. Corticosteroids inhibiting PLA₂ (upstream) vs NSAIDs inhibiting COX (downstream) is a high-yield distinction.
⚠ Common Trap
Students confuse prostaglandins and thromboxanes — both come from the COX pathway but have different roles: prostaglandins cause inflammation/vasodilation; TXA₂ promotes platelet aggregation/vasoconstriction. Also: leukotrienes come from LOX (not COX) — NSAIDs do NOT block leukotriene synthesis, which is why they don't treat asthma.
✓ Quick Self-Check
1. What is the precursor for all eicosanoids?
Arachidonic acid (20:4 ω-6) — a 20-carbon polyunsaturated fatty acid released from membrane phospholipids by phospholipase A₂.
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2. What does the COX pathway produce?
Prostaglandins (inflammation, pain, fever, vasodilation) and thromboxanes (TXA₂ — platelet aggregation, vasoconstriction).
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3. What does the LOX pathway produce?
Leukotrienes — mediators of inflammation and bronchoconstriction (key in asthma).
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4. How do NSAIDs work?
They inhibit cyclooxygenase (COX-1 and/or COX-2), blocking prostaglandin and thromboxane synthesis. Aspirin does so irreversibly; ibuprofen reversibly.
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5. Why don't NSAIDs treat asthma?
Asthma is mediated by leukotrienes from the LOX pathway — NSAIDs block COX, not LOX. Leukotriene antagonists (montelukast) are used instead.
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