ALOX5

ALOX5, or arachidonate 5-lipoxygenase, is a non-heme iron-containing enzyme that plays a central role in the biosynthesis of leukotrienes, lipid mediators involved in inflammation and allergic responses. The human ALOX5 gene encodes the 5-LO enzyme, which is primarily expressed in white blood cells such as neutrophils, eosinophils, monocytes, and mast cells.

In the inflammatory pathway, arachidonic acid released from membrane phospholipids is converted by 5-LO into 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and then to leukotriene A4 (LTA4). LTA4 serves as a branch point: it can be hydrolyzed to leukotriene B4 (LTB4), a potent neutrophil chemoattractant, or converted to cysteinyl leukotrienes (LTC4, LTD4, LTE4) that promote bronchoconstriction, vascular permeability, and mucus secretion. Activation of 5-LO requires the 5-LO–activating protein (FLAP) and occurs in the nuclear membrane region of cells. The enzyme is regulated by intracellular calcium, calmodulin, and phosphorylation, reflecting integration with other signaling pathways.

Genetically, the ALOX5 promoter contains a variable number of tandem repeats in a Sp1-binding region, and the repeat number can influence transcriptional activity and leukotriene production. Associations have been studied between ALOX5 variants and susceptibility to asthma or aspirin-exacerbated respiratory disease, though findings are not consistently replicated.

Clinically, inhibition of 5-LOX (for example, with zileuton) reduces leukotriene synthesis and is used in asthma management. Other anti-leukotriene therapies target leukotriene receptors rather than synthesis.