Oxidative metabolites lipoxygenase

Hazai, E, Z Bikadi, F Zsila, and SF. Lockwood. 2006. Molecular modeling of the non-covalent binding of the dietary tomato carotenoids lycopene and lycophill, and selected oxidative metabolites with 5-lipoxygenase. Bio Med Chem 14 6859-6867. 

Besides the design of synthetic molecules, several papers reported the presence of specific enzymatic reactions able to produce also in the cells compounds able to act as reversible FAAH inhibitors (Maccarrone and Finazzi-Agro, 2004a). In particular, it has been found that oxidative metabolites of AEA generated by various lipoxygenases, i.e. the hydroxyanandamides (HAEAs see 12-OH-AEA in Table 4.1), are powerful inhibitors of FAAH (van der Stelt et al., 2002). Instead, derivatives of AEA generated by cyclooxygenase-2, and termed prosta-mides, have been recently shown to be inelfective on FAAH activity (Matias et al., 2004). 

Fig. 12. Metabolism of arachidonic acid by cytochrome P-450 enzymes and the formation of three structurally distinct metabolite families.

Glutathione peroxidase is a selenium-dependent enzyme, which rapidly detoxifies hydrogen peroxide and various hydroperoxides. Suttorp et al. [67] showed that the impairment of glutathione cycle resulted in an increase in the injury of pulmonary artery endothelial cells. Glutathione cycle protected against endothelial cell injury induced by 15-HPETE, an arachi-donate metabolite produced by 15-lipoxygenase-catalyzed oxidation [68]. 

Other metabolic routes involve oxidative transformations that bear close resemblance to the processes that lead to the eicosanoids (Kozak et al., 2000 Kozak, Crews, et al., 2001 Kozak, Prusakiewicz, et al., 2001 Kozak, Crews, et al., 2002 Kozak and Mamett, 2002). For example, both 12- and 15-lipoxygenase products of anandamide are known (Edgemond et al., 1998 Moody et al., 2001 Kozak, Gupta, et al., 2002), as well as a group of P-450-mediated hydroxy anandamide metabolites (Bomheim et al., 1993 Bomheim et al., 1995). Free arachidonic acid is required for COX-1-mediated conversion to PGs, whereas the requirements for COX-2-mediated conversion... 

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