Human 5‐Lipoxygenase

Abstract

The enzyme 5‐lipoxygenase initiates the biosynthesis of leukotrienes, lipid mediators of the inflammatory response. The enzyme is also required for the synthesis of lipoxins, arachidonic‐acid‐derived compounds that promote resolution of inflammation. Lipoxygenases are non‐heme‐iron enzymes that catalyze the peroxidation of polyunsaturated fatty acids. Although all arachidonate‐metabolizing lipoxygenases recognize the same 20‐carbon polyunsaturated fatty acid, each generates a unique product. We describe here the structure of 5‐lipoxygenase, which is distinct among lipoxygenases with respect to the reactions it catalyzes and its regulation. Multiple regulatory mechanisms that combine to ensure a measured generation of its products, precursors of potent signaling compounds, are described. These mechanisms include an atypical (with respect to the lipoxygenase superfamily) protein lability, Ca 2+ ‐induced translocation to the nuclear membrane, and serine phosphorylation.