ABSTRACT
The reaction of molecular oxygen with free arachidonic acid, catalyzed by 5lipoxygenase, leads to the formation of the progenitor leukotriene, namely, leukotriene A4 (LTA4) (1,2). While there is no evidence for any direct LTA4 biological activity, its rapid conversion either into leukotriene B4 (LTB4) or the sulfidopeptide leukotriene [leukotriene C4 (LTC4)] has been the subject of numerous investigations (3,4). It is interesting to note a parallelism between the metabolic conversion of LTA4 into the dihydroxy product LTB4 catalyzed by LTA4 hydrolase and conjugation of LTA4 with glutathione to form LTC4, with the metabolic events known to occur for electrophilic species produced during normal cellular metabolic processes. The reaction of epoxides with epoxide hydrolase (5) or glutathione-S-transferase (6) has been widely studied for many xenobiotics exposed to mammalian cells and tissues. However, the processing of LTA4 within the cell is carried out by rather specific and unique enzymes highlighting the important roles these lipid products play in normal physiology and pathophysiology. While LTA4 hydrolase is widely distributed in most cell types (7), the expression of LTC4 synthase is largely restricted to cells that have been derived from the bone marrow (8).
