The oxidative inactivation of cytochrome P450 in monooxygenase reactions

Possible mechanisms of cytochrome P450 self-inactivation during catalytic turnover have been considered. Two ways of hemoprotein inactivation are so far known. The first, studied extensively by many authors, is the formation of active substrate intermediates, capable of modifying heme and apoenzyme. The second way, revealed quite recently and resulting from uncoupled cytochrome P450-catalyzed monooxygenase reactions, is yet to be clarified. Briefly, it involves formation of hydrogen peroxide in the hemoprotein active center, which interacts with the enzyme associated Fe2+, thereby generating hydroxyl radicals that bleach the heme and modify the apoenzyme. This mechanism operates with substrates and cytochrome P450 forms with partially coupled monooxygenase reactions, thus causing the formation of hydrogen peroxide as a byproduct.