Leukotrienes (LTs) are produced by the enzymatic oxidation of arachidonic acid (AA) released from cellular membrane (Shimizu 2009; Nakamura and Shimizu 2011). The 5-lipoxygenase (5-LO) cascade is involved in the production of these lipid mediators. Structural differences divide leukotrienes into two groups: (i) leukotriene B4 (LTB4), which contains two hydroxy groups, and (ii) cysteinyl-leukotrienes (Cys-LTs), i.e., LTC4, LTD4 and LTE4, based on the cysteine residue in their structures. LTB4 is synthesized from AA through formation of LTA4. LTB4 is well known as one of the potent chemoattractants and activators of leukocytes, and is involved in inflammatory diseases. LTC4 is also produced via LTA4 by glutathione conjugation of LTA4 with opening of the epoxide at the allylic position C-6. Next, LTC4 is converted to LTD4 by elimination of glutamic acid. The remaining peptide bond in LTD4 is further hydrolyzed by a dipeptidase to generate LTE4. These mediators cause smooth muscle contraction, enhance mucus secretion, recruitment of eosinophils to the airways, and increase vascular permeability, producing edema. They have a relatively short half-life (seconds to minutes), and can be degraded enzymatically.
