[Self-inactivation of cytochrome P-450 in the catalytic cycle]

The paper deals with possible mechanisms of cytochrome p-450 self-activation during catalytic turnover. Two routes of hemoprotein inactivation are so far known. The first route studied extensively by many authors, consists in formation of active intermediates capable of modifying heme and apoenzyme. The second route revealed only lately, which results from uncoupled cytochrome P-450-catalyzed monooxygenase reactions, is yet to be clarified. Briefly, it consists in the fact that the hydrogen peroxide formed in the hemoprotein active center interacts with the enzyme-bound Fe2+, thereby generating hydroxyl radicals that bleach the heme and modify the apoenzyme. This mechanism operates with all the substrates and all cytochrome P-450 forms capable of catalyzing the partially coupled monooxygenase reactions proceeding with the formation of hydrogen peroxide as a by-product.