ABSTRACT
The first committed step in the biological production of leukotrienes is the reaction catalyzed by the 78 kDa enzyme 5-lipoxygenase (5-LO), which results in the formation of the unstable epoxide leukotriene A4 (LTA4). LTA4 is the precursor for the leukocyte activator leukotriene B4 and for the bronchoconstrictive and proinflammatory cysteinyl leukotrienes, leukotriene C4, D4, and E4. In cells, an essential activator of the 5-LO reaction is the 18 kDa membrane-bound protein, 5-lipoxygenase-activating protein (FLAP). This chapter begins with a discussion of the mechanism and expression of 5-LO followed by the genetic knockout and chemical inhibition of 5-LO. The subsequent section discusses the discovery, expression, and inhibition of FLAP.
