Lipoxygenases (LOX) are non-heme iron-containing enzymes that catalyze regio- and stereo-selective dioxygenation of polyunsaturated fatty acids (PUFA). Mammalian LOXs participate in the eicosanoid cascade during the inflammatory response, using preferentially arachidonic acid (AA) as substrate, for the synthesis of leukotrienes (LT) and other oxidized-lipid intermediaries. This review focus on lipoxygenases (LOX) structural and kinetic implications on both catalysis selectivity, as well as the basic and clinical implications of inhibition and interactions with nitric oxide (^•NO) and nitroalkenes pathways. During inflammation ^•NO levels are increasingly favoring the formation of reactive nitrogen species (RNS). ^•NO may act itself as an inhibitor of LOX-mediated lipid oxidation by reacting with lipid peroxyl radicals. Besides, ^•NO may act as an O₂ competitor in the LOX active site, thus displaying a protective role on lipid-peroxidation. Moreover, RNS such as nitrogen dioxide (^•NO₂) may react with lipid-derived species formed during LOX reaction, yielding nitroalkenes (NO₂FA). NO₂FA represents electrophilic compounds that could exert anti-inflammatory actions through the interaction with critical LOX nucleophilic amino acids. We will discuss how nitro-oxidative conditions may limit the availability of common LOX substrates, favoring alternative routes of PUFA metabolization to anti-inflammatory or pro-resolutive pathways.

脂氧合酶（LOX）是一种非血红素铁酶，可催化多不饱和脂肪酸（PUFA）的区域和立体选择性双加氧反应。哺乳动物LOX在炎症反应期间参与类花生酸级联反应，优先使用花生四烯酸（AA）作为底物，以合成白三烯（LT）和其他氧化脂质中间体。这篇综述集中于脂氧合酶（LOX）对催化选择性的结构和动力学影响，以及抑制作用以及与一氧化氮（^• NO）和硝基烯烃途径相互作用的基本和临床意义。炎症期间^• NO水平越来越倾向于形成活性氮（RNS）。^•NO可能通过与脂质过氧自由基反应而自身充当LOX介导的脂质氧化的抑制剂。此外，^• NO可能在LOX活性位点充当O ₂竞争者，因此对脂质过氧化具有保护作用。此外，RNS（例如二氧化氮（^• NO ₂））可能会与在LOX反应过程中形成的源自脂质的物质反应，生成硝基烯烃（NO ₂ FA）。NO ₂FA代表可以通过与关键LOX亲核氨基酸相互作用而发挥抗炎作用的亲电子化合物。我们将讨论硝基氧化条件如何限制常见LOX底物的可用性，从而促进PUFA代谢的替代途径成为抗炎或促溶途径。