Cytochrome P450, catalysis, electron

The mechanism of cytochrome P450 catalysis is probably constant across the system. It is determined by the ability of a high valent formal (FeO) species to carry out one-electron oxidations through the abstraction of hydrogen atoms or electrons. The resultant substrate radical can then recombine with the newly created hydroxyl radical (oxygen rebound) to form the oxidized metabolite. Where a heteroatom is the (rich) source of the electron more than one product is possible. There can be direct recombination to yield the heteroatom oxide or radical relocalization within the... 

One of the most intriguing reactions in the chytochrome P450 catalysis is the transfer of second electron and dioxygen activation, which appears to be a key step of the entire process. The chemical nature of reactive oxidizing species appears in the coordination sphere of heme iron and the mechanism of hydroxylation of organic compounds, saturated hydrocarbons in particular, is a much debated question in the field of the cytochrome P450 catalysis. To solve this problem, an entire arsenal of modern experimental and theoretical methods are employed. The catalytic pathway of cytochrome P450cam from Pseudomonas putida obtained on the basis of X-ray analysis at atomic resolution is presented in Fig. 3.10. 

NADPH cytochrome P450 reductase, an enzyme containing which a complex flavoenzyme that contains two flavins, one electron is first intramolecularly transferred from FAD to FMN, before the reaction with cytochrome P450 takes place. With FNR, NADP+ first has to bind to the oxidized form, before the very fast one-electron transfer from the specifically interacting reduced ferredoxin (Fdred) occurs (8). Subsequent dissociation of the oxidized ferredoxin (Fdox) is rate-limiting in catalysis. The enzyme semiquinone-NADP" complex then reacts with another reduced ferredoxin molecule to yield the flavin hydroquinone state. In the final steps of the catalytic cycle, the NADP+ is reduced and the NADPH dissociates ... 

Hanna IH, Kim MS, Guengerich FP. Heterologous expression of cytochrome P450 2D6 mutants, electron transfer, and catalysis of bufuralol hydroxylation the role of aspartate 301 in structural integrity. Arch Biochem Biophys 2001 393 255-61. 

Monooxvgenases. These enzymes are important in the detoxication of pyrethroid, carbamate, organophosphorus and other classes of insecticides (2). They are microsomal, membrane associated enzymes which catalyze reactions in which one atom from molecular oxygen is inserted into the insecticide and the second oxygen atom is reduced to form water. Catalysis depends on the close association of the heme-containing cytochrome P450 terminal oxidase with NADPH cytochrome C reductase for electron transport, and it also depends on availability of NADPH and oxygen. 

Substrate binding to cytochrome P450 is an important step in the overall mechanism of P450 catalysis, not only because it is necessary to position the substrate in the proper orientation in the immediate vicinity of the heme bound catalyti-cally competent active oxygen. Equally important, it serves as the trigger activating the electron... 

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