15LOX

15-lipoxygenase (15-LOX) refers to a group of non-heme iron–containing enzymes that catalyze the insertion of molecular oxygen into polyunsaturated fatty acids at the 15th carbon. The primary human substrate is arachidonic acid, which is converted to 15-hydroperoxyeicosatetraenoic acid (15-HPETE) and subsequently to 15-hydroxyeicosatetraenoic acid (15-HETE). 15-LOX activity also acts on other fatty acids, producing a range of hydroxy and hydroperoxy products that feed into lipid mediator pathways.

In humans, the two main isoforms are ALOX15 (15-LOX-1) and ALOX15B (15-LOX-2). Both enzymes can oxygenate arachidonic acid to 15-HETE, but they differ in tissue distribution and substrate preferences. ALOX15 is more associated with monocytes/macrophages and certain epithelial cells and can also convert linoleic acid to 13-HODE, linking 15-LOX activity to multiple fatty acid–derived mediators. ALOX15B has a distinct expression pattern and may contribute to 15-HETE production in other tissues.

Biological roles of 15-LOX include participation in inflammatory responses and the resolution of inflammation. 15-LOX–generated products are involved in the biosynthesis of lipoxins, lipid mediators that promote the return to tissue homeostasis. The enzyme pathway intersects with other lipoxygenase routes (notably 5-LOX) in transcellular lipid mediator biosynthesis. Dysregulation of 15-LOX activity has been investigated in conditions such as atherosclerosis, asthma, fibrosis, and cancer, highlighting its potential as a target for therapeutic intervention.

Beyond humans, 15-LOX–related enzymes are found in other organisms, including plants, where LOX family members participate in oxylipin signaling and defense responses.