Arachidonate 5-lipoxygenase (5-LO) (5-LO)

Arachidonate 5-lipoxygenase (5-LO) is the key enzyme responsible for the initial steps in the biosynthesis of leukotrienes, which are potent lipid mediators of inflammation (UniProt P09917). It is primarily expressed in leukocytes, such as neutrophils, eosinophils, and macrophages, and requires the 5-lipoxygenase-activating protein (FLAP) for its catalytic activity at the nuclear membrane (PubMed PMID: 30103123). The 5-LO pathway converts arachidonic acid into leukotriene A4, which is then processed into leukotriene B4 (a potent chemoattractant) or cysteinyl leukotrienes (drivers of bronchoconstriction and edema) (NCBI Gene ID: 240). Because of its central role in mediating inflammatory and allergic responses, 5-LO is a major therapeutic target for respiratory conditions like asthma and allergic rhinitis. Drugs such as Zileuton act by directly inhibiting the 5-LO enzyme, thereby reducing the production of all downstream leukotrienes and alleviating airway inflammation (StatPearls: Zileuton). Additionally, the pathway is increasingly recognized for its involvement in cardiovascular diseases and certain types of cancer, suggesting broader clinical utility for 5-LO inhibitors.

Other names

ALOX55-LOX5-lipoxygenaseLOG5Arachidonate 5-lipoxygenase

Direct inhibition of the 5-lipoxygenase enzyme, preventing the conversion of arachidonic acid to 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and subsequently leukotriene A4 (LTA4), thereby blocking the production of all downstream leukotrienes (LTB4, LTC4, LTD4, and LTE4).