Leukotriene B4 (LTB4) biosynthesis pathway (LTB4 pathway)

The Leukotriene B4 (LTB4) biosynthesis pathway is a metabolic sequence within the arachidonic acid cascade that generates potent proinflammatory lipid mediators (StatPearls: NBK546601). The pathway is initiated by the enzyme 5-lipoxygenase (5-LOX), which, with the assistance of 5-lipoxygenase-activating protein (FLAP), converts arachidonic acid into the unstable intermediate leukotriene A4 (LTA4) (UniProt: P09917). LTA4 is then converted by leukotriene A4 hydrolase (LTA4H) into LTB4, a powerful chemoattractant for neutrophils and other leukocytes (UniProt: P09960). LTB4 plays a central role in the recruitment and activation of immune cells, contributing to the pathogenesis of chronic inflammatory diseases such as asthma, COPD, and rheumatoid arthritis (PubMed: 29736390). Pharmacological intervention typically involves the use of 5-LOX inhibitors like zileuton, FLAP inhibitors, or LTA4H inhibitors like acebilustat to block the production of LTB4 and reduce inflammation (PubChem: CID 60490; ClinicalTrials.gov: NCT02443688). While these drugs offer therapeutic benefits, they can be associated with safety concerns like hepatotoxicity, as seen with the 5-LOX inhibitor zileuton. Monitoring LTB4 levels in biological fluids serves as a key biomarker for assessing pathway activity and drug efficacy.

Other names

5-Lipoxygenase pathwayArachidonic acid 5-lipoxygenase pathwayLTB4 synthesis pathway

Inhibition of 5-lipoxygenase (5-LOX), 5-lipoxygenase-activating protein (FLAP), or leukotriene A4 hydrolase (LTA4H) to prevent the synthesis of the proinflammatory mediator LTB4.