ABSTRACT
Arachidonic acid (AA) is converted to a large number of biologically active products by cyclooxygenases, lipoxygenases, and cytochrome P450 enzymes (Funk, 2001). The most important of these are the cyclooxygenase and 5-lipoxygenase (5-LO) pathways, which result in the formation of prostanoids and leukotrienes (LTs). In some cases, different oxygenases cooperate to produce additional products such as the lipoxins (Schwab and Serhan, 2006). 5-LO oxygenates AA at the 5-position to give 5S-hydroperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HpETE), which it then cyclizes to LTA4 (Figure 7.1). LTA4 is converted to LTB4 by LTA4 hydrolase and to the cysteinyl-LT LTC4 by LTC4 synthase (Murphy and Gijon, 2007). Alternatively, if relatively large amounts of LTA4 are formed, it decomposes nonenzymatically to biologically inactive 6-trans isomers of LTB4. A signi™cant amount of 5-HpETE is normally lost from 5-LO and is reduced by peroxidases such as glutathione peroxidase to 5S-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HETE) (Rådmark et al., 2007).
