Arachidonate 5-lipoxygenase (ALOX5) (ALOX5)

Arachidonate 5-lipoxygenase (ALOX5), also known as 5-lipoxygenase (5-LOX), is the central enzyme in the biosynthetic pathway that converts arachidonic acid into leukotrienes, which are critical lipid mediators of the inflammatory response [2, 9]. The pathway begins with the translocation of 5-LOX to the nuclear envelope, where it works in conjunction with the 5-lipoxygenase-activating protein (FLAP) to produce leukotriene A4 (LTA4) [1, 5]. LTA4 is then converted by leukotriene A4 hydrolase (LTA4H) into leukotriene B4 (LTB4), a potent chemoattractant that recruits and activates neutrophils and other leukocytes [3, 10]. Overactivation of this pathway is a hallmark of various inflammatory conditions, including asthma, rheumatoid arthritis, and atherosclerosis, and it has also been implicated in the progression of certain cancers and neurodegenerative diseases like Alzheimer's [5, 11, 14]. Therapeutic strategies targeting this pathway include direct 5-LOX inhibitors such as zileuton, FLAP inhibitors, and specific LTA4H inhibitors or BLT1 receptor antagonists designed to block LTB4-mediated inflammation [3, 13]. While these drugs offer significant anti-inflammatory benefits, clinical use is sometimes limited by safety concerns such as hepatotoxicity and potential neuropsychiatric side effects [16].

Other names

5-lipoxygenase5-LOX5-LOALOX55-lipoxygenase / leukotriene B4 formation pathwayArachidonate 5-lipoxygenase-activating protein (FLAP)Leukotriene A4 hydrolase (LTA4H)

Inhibition of the 5-lipoxygenase enzyme or its activating protein (FLAP) to prevent the synthesis of leukotriene A4, or inhibition of leukotriene A4 hydrolase to specifically block the formation of the pro-inflammatory mediator leukotriene B4.