9. Conclusions
Cytochrome P450 mechanisms continue to surprise and delight, although the field is growing to maturity and the completely unexpected is less frequently encountered. Experimentally, the past few years have seen major progress in characterizing the intermediates that are formed as molecular oxygen is activated to the final oxidizing species. All the intermediates, with the exception of the critical ferryl species, have now been directly observed by various spectroscopic and crystallographic methods. The ferric peroxo anion has been found to act as the oxidizing agent with a growing range of highly electrophilic substrates. In contrast, the proposed role for the ferric hydroperoxo complex as an electrophilic oxidizing agent remains a matter of debate, as the evidence advanced in support of the proposal is circumstantial and contradictory. Although the ferryl species remains elusive, it is increasingly clear that it plays the predominant role as the oxidizing agent in the P450 catalytic cycle. A second area that has recently received considerable attention is the mechanism of hydrocarbon hydroxylation, the key question being whether the radical rebound mechanism that has held sway for three decades is in fact valid. The contradictory results obtained with radical and cation probes, which have provided most of the new evidence, must be resolved by further experimentation in order for this quest ionto be settled. The development of a two-state model for the catalytic action of P450 enzymes may be one of the most important recent advances in the field, as it provides a ready explanation for a variety of otherwise contradictory data, some of which argues for concerted and some for nonconcerted oxidation mechanisms. No doubt, the next few years will uncover novel aspects of P450 function and will lead to deeper and more sophisticated understanding of the catalytic mechanisms of the amazing family of P450 enzymes.
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Ortiz de Montellano, P.R., De Voss, J.J. (2005). Substrate Oxidation by Cytochrome P450 Enzymes. In: Ortiz de Montellano, P.R. (eds) Cytochrome P450. Springer, Boston, MA. https://doi.org/10.1007/0-387-27447-2_6
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