NADPH dioxygen activation

A reduction and activation of HjOj by other one-electron donors, like semiquinones, has also to be considered. This follows from a study of the ethylene production from methionine in the presence of pyridoxal phosphate, a reaction characteristic for OH radicals or for Fenton-type oxidants. The ethylene production in the presence of dioxygen, anthraquinone-2-sulfonate, and an NADPH-generating system in phosphate buffer pH 7.6 was inhibited by SOD and by catalase, but stimulated by scavengers of OH radicals, like 0.1 mM mannitol, a-tocopherol, and formiate... 

Cytochrome P-450-dependent monooxygenases are widely distributed in living organisms (e.g., mammals, insects, fish, yeasts, plants). In humans, they exist in several organs and tissues with a maximum level in the liver. These monooxygenases are multienzymatic systems that are able to transfer electrons from NADPH or NADH to their terminal component, cytochrome P-450, which contains the site of activation of dioxygen and substrates. They catalyze the insertion of only one oxygen atom of 02 into the substrate (Eq. 7). 

The enzymes reductively activate dioxygen using NADPH as an electron source. One oxygen atom is then reduced to water and the other atom is transferred to a substrate, resulting in the hydroxylation of alkenes and arenes, the epoxidation of alkenes and the formation of N-oxides and S-oxides from amino and sulphur compounds. Other P-450 reactions include N-dealkylation, O-dealkylation and reductase-like dehalogenation of halocarbons. Typical P-450 reactions are summarised in Ihble 5-4. 

In vivo, the source of protons and electrons necessary to generate the active, formally oxoiron(V) oxidant from the iron(II) dioxygen complex is provided by the cofactor NADPH. Synthetic models have long been studied by chemists in... 

Any of these ROS could oxidize an organic substrate with the net insertion of an oxygen atom. In each case, reductive reactions are required for activation of dioxygen to one of the ROS from electrons supplied by NADPH. The generation of a carbon-... 

---