5-Lipoxygenase: mechanisms of regulation

Abstract

5-lipoxygenase (5-LO) catalyzes two steps in biosynthesis of leukotrienes (LTs), a group of lipid mediators of inflammation derived from arachidonic acid (AA). LT antagonists are used in treatment of asthma; more recently a potential role also in atherosclerosis has raised considerable interest. Furthermore, possible effects of 5-LO metabolites in relation to tumorigenesis have emerged. Thus, an understanding of the biochemistry of this lipoxygenase has potential implications for treatment of various diseases.

Fig. 1.

The human 5-Lipoxygenase (5-LO) gene (71.9 kilobases) is localized on chromosome 10, and it is divided into 14 exons.

Fig. 2.

Model structure of 5-LO (generated with RasMol) based on the crystal structure for the ferrous form of rabbit reticulocyte 15-LO (PDB: 1LOX) (21). ERK1/2, extracellular signal-regulated kinase; MK2, mitogen-activated protein kinase activated protein (MAPKAP) kinase 2; PKA, protein kinase A. Inserts show the ligands to iron in 5-LO and the structure of coactosin-like protein (CLP) (PDB: 1WNJ) (51).