Eicosanoid Metabolism: Prostaglandins, Thromboxanes & Leukotrienes
| Rate-Limiting Release: | Phospholipase A2 (Cleaves Arachidonic Acid from membrane) |
| Cyclooxygenase (COX) Path: | Prostaglandins, Prostacyclin & Thromboxanes |
| Lipoxygenase (LOX) Path: | Leukotrienes & Lipoxins (5-LOX requires FLAP) |
| Corticosteroid Blockade: | Annexin A1 / Lipocortin (Directly inhibits Phospholipase A2) |
High-Yield Core Realities:
- The Endothelial-Platelet Tug of War: Thromboxane A2 (TXA2) is synthesized in platelets via COX-1; it drives potent vasoconstriction and platelet aggregation. Conversely, Prostacyclin (PGI2) is produced by vascular endothelial cells via COX-2; it drives vasodilation and strongly inhibits platelet aggregation. Low-dose aspirin selectively and irreversibly acetylates platelet COX-1, shifting the physiological balance toward PGI2-mediated cardioprotection.
- Aspirin-Exacerbated Respiratory Disease (AERD): Shunting arachidonic acid down an alternative route can cause severe side effects. In patients with AERD, blocking the COX pathway with NSAIDs forces all remaining arachidonic acid pools through the 5-Lipoxygenase (5-LOX) pathway. This causes an overproduction of cysteinyl leukotrienes, triggering intense bronchoconstriction, wheezing, and nasal polyposis.
- Leukotriene Functional Signatures: LTB4 serves as a highly potent chemoattractant that recruits and activates neutrophils via upregulating integrin expression. In contrast, the cysteinyl leukotrienes (LTC4, LTD4, LTE4) drive intense smooth muscle contraction, causing the bronchoconstriction and increased vascular permeability seen in asthma and anaphylaxis.
- Gastric Cytoprotection Architecture: PGE2 and PGI2 bind to EP and IP receptors on gastric mucosal cells. This interaction actively inhibits parietal cell cyclic AMP production, reducing gastric acid secretion while simultaneously stimulating the secretion of cytoprotective mucus and bicarbonate. Non-selective NSAIDs halt this protective pathway, which can lead to peptic ulcer disease.
- The Ductus Arteriosus Switch: During fetal development, low oxygen tension combined with placenta-derived PGE2 keeps the ductus arteriosus open. At birth, placental separation drops PGE2 levels precipitously, triggering ductal closure. In cases of patent ductus arteriosus (PDA), clinicians administer indomethacin (a potent COX inhibitor) to shut it, whereas keeping a transposition-dependent ductus open requires an infusion of exogenous PGE1 (alprostadil).