Hydroperoxide specificity of plant and human tissue lipoxygenase: an in vitro evaluation using N-demethylation of phenothiazines

Lipoxygenase - a versatile biocatalyst for biotransformation of endobiotics and xenobiotics

“…Subsequent reports have confirmed these observations for SLO [71 -75] as well as human tissue LOs [75]. A recent study from our laboratory [76] has revealed that synthetic organic peroxides such as tert-butyl hydroperoxide or cumene hydroperoxide can also support xenobiotic oxidation by SLO or HTPLO with notable efficiency. …”

“…A similar structure-activity response was displayed by HTPLO for N-demethylation of phenothiazines. Cumene hydroperoxide and tert-butyl hydroperoxide also support the reaction (table 3) [76]. Additional experimental evidence [130] revealed that PUFAs also support N-dealkylation of phenothiazines by SLO and HTPLO.…”

“…HTPLO can also produce CPZ +• from CPZ in the presence of H 2 O 2 [129]. Recent studies indicate that besides H 2 O 2 , the SLO-and HTPLO-catalyzed CPZ +• genesis from CPZ is also efficiently supported by PUFAs [130], cumene hydroperoxide, and tertbutyl hydroperoxide [76].…”

“…The experimental data gathered in our laboratory on the structure-activity relationship of xenobiotics undergoing dealkylation suggest that the accessibility of the N atom-bearing methyl groups is critical for N-demethylation. Thus, compounds such as antipyrine, theophylline, caffeine, nicotine, and cocaine in which the N atom bearing the alkyl groups is endocyclic and which are known [63] or synthetic organic hydroperoxides [76]. The absence of detectable O-dealkylation of 4-nitroanisole or S-dealkylation of methiocarb clearly marks a unique substrate specificity exhibited by the LO pathway (SLO) for dealkylation of xenobiotics [131].…”

Lipoxygenase-Quercetin Interaction: A Kinetic Study Through Biochemical and Spectroscopy Approaches

“…This compound, or the peroxide, supports the cooxidase activity of lipoxygenase toward a suitable electron donor, which is transformed into a radical (Pinto & Macias, 2005). The hydroperoxidase activity of LOX also can be observed in the presence of hydrogen peroxide instead of lipid hydroperoxide, being related to xenobiotic oxidation processes (Hover & Kulkarni, 2000;Santano b et al, 2002). In addition, it is known that a variety of phenolic compounds and flavonoids with antioxidant properties are inhibitors of lipoxygenase (Prasad et al, 2004).…”