Cytochromes P450 electron transfer

Filatov, M., Harris, N., and Shaik, S. (1999) On the "rebound" mechanism of alkane hydroxylation by cytochrome P450 electronic structure of the intermediate and the electron transfer character in the rebound step. Angew. Chem., Int. Ed. 38, 3510-3512. 

Protein-mediated electron transfer is a device used in a diverse array of biological transformadons. Well-known electron transfer processes include the mitochondrial electron transport system, photosynthesis (Chapter 13), and nitrogen flxadon (Chapter 15). Less well known biochemical reactions in which electron transfer plays a crucial role include nitric oxide synthesis and the cytochrome P450 electron transport systems. Each of these mechanisms is briefly oudined. 

Scheme 10.3 Electron-transport systems associated with cytochrome P450 monooxygenases. Arrows indicate electron transfer.

Biosensors based on direct electron transfer of proteins cytochrome P450 [218]... 

D. Wired Cytochrome P450 VI. Double Electron Transfer... 

Table 12 shows redox properties of some redox systems of biochemical nature. Generally, the redox potentials are modest, cytochrome P450 possibly being an exception. If cytochrome P450 functions as an electron transfer oxidant towards xenobiotic molecules, it is necessary to postulate a considerably higher potential (1.3-1.8V) from considerations of the Marcus theory (Eberson, 1990). 

Dihaloelimination is a two-electron transfer reaction. Thompson et al. [377] reported reductive dichloroelimination of 1,1,2-TCA and TeCA by hepatic micro-somes from rat Ever, with VC and both tDCE and cDCE as metabolites. Reductive dichloroelimination from hexa- and pentachloroethane by microsomal cytochrome P450 was studied by Nastainczyk et al. [378]. The main products of the in vitro metabolism of hexa- and pentachloroethane were PCE (99.5%) and TCE (96%), respectively, with minor amounts of pentachloroethane (0.5%) and TeCA (4%), respectively, via reductive dechlorination. 

Robin MA, Anandatheerthavarada HK, Fang JK, Cudic M, Otvos L, et al. 2001. Mitochondrial targeted cytochrome P450 2E1 (P450 MT5) contains an intact N terminus and requires mitochondrial specific electron transfer proteins for activity. J Biol Chem 276 24680-24689. 

Fig. 5. Catalytic cycle of cytochrome P450. The substrate HR binds to the resting enzyme A to form intermediate B, which is reduced by one electron to form C and then reacts with dioxygen. The resulting ferric-peroxo intermediate D is reduced by one equivalent to form the transient oxyferrous intermediate E, which proceeds quickly to intermediate F with release of a molecule of water. F is designated Fe(V)=0 to indicate that it is oxidized by two equivalents greater than A and not to imply anything about the true oxidation state of the iron. Intermediate F then transfers an oxygen atom to the substrate to regenerate the resting enzyme. The peroxide shunt refers to the reaction of B with hydrogen peroxide to produce the intermediate F, which can then proceed to product formation.

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