Lipoxygenase and Leukotriene Pathways: Biochemistry, Biology, and Roles in Disease

Lipoxygenase reactions are catalyzed by nonheme iron-containing dioxygenases, which introduce molecular oxygen into polyunsaturated fatty acids with one or more cis,cis-1,4-pentadiene moieties in the structure.5 9 Please also consult previous reviews. The iron is subsequently oxidized by electron transfer to the peroxy radical, generating a peroxy-anion, which subsequently is protonated to give the hydroperoxide and active enzyme. The hydrogen abstraction and insertion of oxygen occur on opposite sides of the substrate. Plant lipoxygenases have been extensively studied, and soybean lipoxygenase was purified and crystallized already in 1947. An S chirality of the hydroperoxide product was long believed to be a hallmark for a lipoxygenase-catalyzed reaction. However, it is now well established that lipoxygenases can also remove a pro-R hydrogen from the substrate with antarafacial insertion of oxygen to generate products with R chirality.