Leukotriene B4 formation pathway (LTB4 pathway)

The Leukotriene B4 (LTB4) formation pathway is a critical metabolic route within the arachidonic acid cascade responsible for producing potent pro-inflammatory mediators (Haeggström & Funk, 2011). It begins with the release of arachidonic acid from cell membranes, which is then converted by 5-lipoxygenase (5-LOX), in conjunction with 5-lipoxygenase-activating protein (FLAP), into leukotriene A4 (LTA4). LTA4 is subsequently hydrolyzed by leukotriene A4 hydrolase (LTA4H) to form LTB4, a powerful chemoattractant that recruits and activates neutrophils and other immune cells (Yokomizo et al., 2018). This pathway plays a central role in the pathogenesis of chronic inflammatory diseases such as asthma, COPD, and rheumatoid arthritis. Pharmacological intervention typically focuses on inhibiting 5-LOX, FLAP, or LTA4H to reduce LTB4 production and dampen the inflammatory response (PubChem CID 60491). While effective in certain conditions, targeting this pathway requires careful monitoring for side effects like hepatotoxicity and potential impacts on systemic immune surveillance (FDA Zileuton Label).

Other names

5-Lipoxygenase pathwayArachidonic acid 5-lipoxygenase pathwayLTB4 biosynthetic pathway5-LOX/LTA4H pathway

Inhibition of key enzymes such as 5-lipoxygenase (5-LOX) or leukotriene A4 hydrolase (LTA4H), or the 5-lipoxygenase-activating protein (FLAP), to block the biosynthesis of the pro-inflammatory mediator leukotriene B4 (LTB4).