Arachidonate 5-lipoxygenase (5-LOX) and Arachidonate 15-lipoxygenase (15-LOX) (5-LOX/15-LOX)

Arachidonate 5-lipoxygenase (5-LOX) and Arachidonate 15-lipoxygenase (15-LOX) are non-heme iron-containing enzymes that play pivotal roles in the oxygenation of polyunsaturated fatty acids, particularly arachidonic acid [1, 2]. 5-LOX is the rate-limiting enzyme in the production of pro-inflammatory leukotrienes, which are key mediators in respiratory diseases like asthma and allergic rhinitis [1, 10]. 15-LOX contributes to the formation of 15-hydroxyeicosatetraenoic acid (15-HETE) and is involved in both the initiation and resolution of inflammation, as well as the development of atherosclerosis and certain malignancies [5, 12, 23]. These enzymes are often targeted together in drug discovery to achieve a more comprehensive anti-inflammatory effect and to modulate the balance between pro-inflammatory and pro-resolving lipid mediators [9, 13]. While 5-LOX inhibitors like zileuton are clinically used for asthma, dual inhibitors and 15-LOX-specific agents are being explored for their potential in treating chronic inflammatory, cardiovascular, and neurodegenerative disorders [7, 15, 22]. The interaction between these pathways is complex, as 15-LOX products can sometimes antagonize 5-LOX-mediated inflammation or serve as precursors for anti-inflammatory lipoxins [12, 13]. Pharmacological modulation of these targets requires careful consideration of the shunting effect, where inhibiting one pathway may increase substrate availability for another, such as the cyclooxygenase pathway [16, 21].

Other names

ALOX5ALOX155-LO15-LO12/15-LOX15-LOX-15-lipoxygenase15-lipoxygenase

Direct inhibition of enzyme activity through iron-ligand binding, redox-type interference with the catalytic iron atom, or non-redox competitive inhibition at the active site [7, 23].