During acute inflammation, leukotriene B4 (LTB4) is produced by neutrophils via 5-lipoxygenase. Which specific phospholipid precursor is first liberated and what is the direct enzyme responsible for LTB4 generation from 5-HPETE?

• A Eicosapentaenoic acid is liberated by COX-2; 5-HPETE is converted to LTB4 by LTB4 synthase
• B Arachidonic acid is liberated from membrane phospholipids by phospholipase A2; 5-HPETE is converted to LTA4 by LTA4 synthase activity of 5-LOX; LTA4 is then hydrated to LTB4 by LTA4 hydrolase ✓
• C Linoleic acid is liberated by phospholipase C; LTB4 is formed directly from 5-HPETE by leukotriene dehydrogenase
• D Arachidonic acid is first converted to thromboxane A2 by thromboxane synthase before generating LTB4

Explanation

Leukotriene biosynthesis begins with phospholipase A2 (cPLA2) cleaving arachidonic acid from membrane phosphatidylcholine/phosphatidylethanolamine. 5-lipoxygenase (5-LOX), in complex with FLAP (5-LOX activating protein), oxygenates arachidonic acid to 5-HPETE, then dehydrates it to the epoxide leukotriene A4 (LTA4) — the pivotal intermediate. LTA4 hydrolase then opens the epoxide ring to yield LTB4 (potent neutrophil chemoattractant/activator). Alternatively, LTA4 is conjugated with glutathione by LTC4 synthase to form the cysteinyl leukotrienes (LTC4, LTD4, LE4). Thromboxane A2 is a COX-pathway product, not related to LTB4 synthesis.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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