Arachidonic acid (all-cis-5, 8, 11, 14-eicosatetraenoic acid, AA) is an essential constituent of cellular membranes, which is released by tightly regulated phospholipase cleavage. Additionally, AA is a key biological intermediate that is converted to a large number of eicosanoids with potent physiological activities (Figure 1). These eicosanoids are synthesized de novo from AA by pathways of oxidative lipid metabolism in a controlled fashion. In 1976, it was found that AA is oxygenated at the C-5 position in a study of the transformation of polyunsaturated fatty acids in rabbit leukocytes. 1 The major metabolite in this reaction, which is mediated by 5-lipoxygenase (5-LO), is 5 (S)-hydroxy-6, 8, 11, 14-eicosatetraenoic acid [5 (S)-HETE]. Subsequently, various derivatives, including leukotriene B4 (LTB4), were identified. 2À4 LTB4 is well-known as one of the potent chemoattractants and activators of leukocytes and is involved in inflammatory diseases. 5, 6 The 5-LO pathway is also involved in the production of five series of LTs, eg, LTB5, from EPA [eicosa-5 (Z), 8 (Z), 11 (Z), 14 (Z), 17 (Z)-pentaenoic acid]. 7, 8 These lipids have less pro-inflammatory and vasoactive activities compared to LTB4. 9 Moreover, extensive studies led to the discovery of the pivotal epoxide intermediate, LTA4, 10 and the identification of a cysteinyl-leukotriene (cys-LT) family, ie, LTC4, LTD4, and LTE4, also known as SRS-A (slow-reacting substance of anaphylaxis). 11 LTC4 is converted from AA, namely, formation of LTA4 from AA via 5 (S)-HpETE, followed by glutathione conjugation of LTA4 with opening of the epoxide at the allylic position C-6. 11, 12 LTC4 is further metabolized to LTD4 by enzymatic elimination of glutamic acid by γ-glutamyltranspeptidase. 13 The remaining peptide bond in