Cytochrome P450, catalysis, electron transfer

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 ... 

Natural proteides like hemoglobin, myoglobin, peroxidase, catalase, cytochrom a, b, P450, desoxigenase and chlorophyll contain the porphyrin system as a prostetic group. The porphyrin is bound coordinatively through the metal atom to the natural polymer or inserted in lipid-protein layers. Important properties are binding of small molecules, catalysis and electron transfer reactions. 

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. 

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