Karuzina I I, Archakov A I
Institute of Biological and Medical Chemistry, Russian Academy of Medical Sciences, Moscow.
Free Radic Biol Med. 1994 Jan;16(1):73-97. doi: 10.1016/0891-5849(94)90245-3.
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.
催化周转过程中细胞色素P450自失活的可能机制已被探讨。目前已知血红素蛋白失活的两种方式。第一种是许多作者广泛研究的，即形成能够修饰血红素和脱辅基酶的活性底物中间体。第二种方式是最近才发现的，由细胞色素P450催化的单加氧酶反应解偶联导致，目前尚待阐明。简而言之，它涉及在血红素蛋白活性中心形成过氧化氢，过氧化氢与酶结合的Fe2+相互作用，从而产生漂白血红素并修饰脱辅基酶的羟基自由基。这种机制在底物和细胞色素P450形式的单加氧酶反应部分解偶联时起作用，从而导致过氧化氢作为副产物形成。
