Prostaglandin and leukotriene synthesis pathways (null)

The prostaglandin and leukotriene synthesis pathways are interconnected enzymatic cascades that convert membrane arachidonic acid into bioactive eicosanoids with potent autocrine and paracrine actions.[1][9][10][13] Prostaglandins and thromboxanes are generated via the cyclooxygenase (COX‑1 and COX‑2) pathway, which produces the common intermediate PGH2 that is further transformed by specific terminal synthases into distinct prostanoids such as PGE2, PGD2, PGF2α, prostacyclin (PGI2), and thromboxane A2.[1][2] Leukotrienes are synthesized through the 5‑lipoxygenase pathway, involving 5‑LOX, accessory proteins such as FLAP, and downstream enzymes including LTA4 hydrolase and LTC4 synthase to yield LTB4 and the cysteinyl leukotrienes LTC4, LTD4, and LTE4.[1][4][6][9] These mediators regulate vasodilation, vascular permeability, platelet aggregation, smooth muscle tone, pain perception, and diverse immune and allergic responses, making the pathways central to inflammation, cardiovascular homeostasis, and host defense.[1][2][8][9] Dysregulated prostaglandin and leukotriene production contributes to diseases such as asthma and allergic airway disease, arthritis, cardiovascular disorders, and cancer.[4][6][8][9][12] Multiple drug classes exploit these pathways therapeutically, including non‑steroidal anti‑inflammatory drugs that inhibit COX isoenzymes, leukotriene receptor antagonists and 5‑LOX inhibitors used in respiratory disease, and experimental agents targeting microsomal PGE2 synthase‑1 or other leukotriene biosynthetic enzymes.[3][4][6][9][12] However, systemic modulation of these pathways can lead to gastrointestinal, renal, and cardiovascular toxicities, reflecting the wide physiological roles of eicosanoids and underscoring the challenge of achieving efficacy while preserving homeostatic functions.[2][12]

Other names

arachidonic acid–eicosanoid biosynthesis pathwayprostaglandin biosynthesis pathwayleukotriene biosynthesis pathwayeicosanoid synthesis pathwaycyclooxygenase and 5-lipoxygenase pathways

Inhibition of cyclooxygenase (COX‑1/COX‑2), reducing prostaglandin, prostacyclin and thromboxane synthesis from arachidonic acid; Inhibition of 5‑lipoxygenase and associated leukotriene biosynthetic enzymes, reducing leukotriene generation; Antagonism of leukotriene receptors (e.g., CysLT1), blocking leukotriene‑mediated signaling; Inhibition of downstream prostaglandin synthases (e.g., mPGES‑1), selectively lowering PGE2 production