Cytochrome oxygenated derivative

Cytochrome P450s catalyze reactions that introduce one atom of oxygen derived from molecular oxygen into the substrate, yielding a hydroxylated product. NADPH and NADPH-cytochrome P450 reductase are involved in the complex reaction mechanism. 

Vaz ADN, Roberts ES, Coon MJ. Olefin Formation in the oxidative deformylation of aldehydes by cytochrome-P-450—mechanistic implications for catalysis by oxygen-derived peroxide. J Am Chem Soc 1991 113(15) 5886-5887. 

M. domestica also hydroxylates and metabolizes alkenes and alkanes to oxygenated derivatives. The epoxide and ketone derivative of (Z)-9-tricosene, (9,10)-epoxytricosane and (Z)-14-tricosene-10-one are derived from the C23 alkene by a cytochrome P450 enzyme which epoxidizes at the 9,10 position and hydroxylates at carbon 10 from the other end of the molecule, and the secondary alcohol is then oxidized to the ketone (Ahmad et al., 1987). 

The overall hydroxylation or epoxidation reaction catalyzed by cytochrome P450s involves the insertion of one oxygen atom, derived from molecular oxygen, into a C-H bond or into the Jt-system of an olefin, with the concomitant reduction of the... 

Colquhoun and Schumacher [98] have shown that y-linolcnic acid and eicosapentaenoic acid, which inhibit Walker tumor growth in vivo, decreased proliferation and apoptotic index in these cells. Development of apoptosis was characterized by the enhancement of the formation of reactive oxygen species and products of lipid peroxidation and was accompanied by a decrease in the activities of mitochondrial complexes I, III, and IV, and the release of cytochrome c and caspase 3-like activation of DNA fragmentation. Earlier, a similar apoptotic mechanism of antitumor activity has been shown for the flavonoid quercetin [99], Kamp et al. [100] suggested that the asbestos-induced apoptosis in alveolar epithelial cells was mediated by iron-derived oxygen species, although authors did not hypothesize about the nature of these species (hydroxyl radicals, hydrogen peroxide, or iron complexes ). 

Such reaction with aromatic hydroperoxides has been studied by Coon and coworkers [54], Instead of hydroperoxides, iodosobenzenes, and iodobezene acetates may participate in Reaction (8) as the oxygen donors [55]. These authors proposed that the reaction of cytochrome P-450 with iodosobenzene proceeds to form an iron-oxo intermediate complex containing only one oxygen atom derived from the substrate. 

The toxicity of dapsone is due to the cytochrome P-450-catalyzed oxygenation leading to iV-hydroxydapsone. This major metabolite enters red cells and is co-oxidized with oxyhemoglobin to generate a nitroso derivative and methemoglobin148. 

---