Arachidonate 5-lipoxygenase (5-LOX) (5-LOX)

Arachidonate 5-lipoxygenase (5-LOX) is a non-heme iron-containing enzyme that serves as the rate-limiting step in the biosynthesis of leukotrienes, which are potent lipid mediators of inflammation derived from arachidonic acid [1, 3]. Upon cellular activation by increased calcium levels, 5-LOX translocates to the nuclear envelope where it interacts with the 5-lipoxygenase-activating protein (FLAP) to catalyze the oxygenation of arachidonic acid into 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and its subsequent dehydration into the unstable epoxide leukotriene A4 (LTA4) [1, 4]. This pathway is primarily active in myeloid cells and is a central driver of the pathophysiology in respiratory diseases such as asthma and allergic rhinitis, where leukotrienes induce potent bronchoconstriction, mucus hypersecretion, and tissue edema [2, 3]. Beyond its established role in pulmonary inflammation, the 5-LOX pathway is increasingly recognized for its involvement in cardiovascular diseases, such as atherosclerosis, and the progression of certain malignancies by promoting cell survival and neoangiogenesis [3, 4]. Pharmacological intervention has focused on direct enzyme inhibitors, like zileuton, which are used to manage chronic asthma, although development of next-generation inhibitors continues to address limitations such as hepatotoxicity and short half-lives [2]. Sources: [1] UniProt (P09917); [2] StatPearls (Leukotriene Antagonists); [3] NCBI Gene (ALOX5); [4] Radmark et al., Trends in Biochemical Sciences.

Other names

5-lipoxygenaseALOX55-LO5LPGArachidonate 5-lipoxygenase

Direct inhibition of the 5-lipoxygenase enzyme, which prevents the initial oxygenation of arachidonic acid to 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and its subsequent conversion to leukotriene A4 (LTA4), thereby blocking the production of pro-inflammatory leukotrienes including LTB4 and the cysteinyl leukotrienes [1, 2].