Lipoxygenase Pathway of the Arachidonate Cascade

Abstract

Abstract Lipoxygenases (LOXs) are iron‐containing enzymes that catalyse the peroxidation of polyunsaturated fatty acids. In mammals, LOX products and their metabolites are potent lipid mediators that provoke diverse biological responses. These eicosanoids, derived from arachidonic acid, play important roles in inflammation and the resolution of inflammation. Moreover, they have been implicated in the development of cardiovascular disease. Although several LOX isoforms are expressed in individual organisms, each generates a specific product. How structurally and mechanistically related enzymes generate different products from a common substrate is not fully understood. In addition, the biological effects of many of the lipid mediators produced through LOX pathways remain to be uncovered. Key Concepts: Arachidonic acid is a substrate for lipoxygenases, iron enzymes that catalyse the peroxidation of polyunsaturated fatty acids. Mammalian lipoxygenases transform the common substrate (arachidonic acid) to a unique stereo‐ and regiospecific product. Leukotriene synthesis is initiated by 5‐lipoxygenase. Lipoxygenase products and their downstream metabolites are potent signalling molecules, some of which play roles in inflammation or its resolution. Lipoxygenase products are associated with cardiovascular diseases, but their molecular mechanism of action remains unclear.