title: Hydrogen peroxide-mediated inactivation of microsomal cytochrome P450 during monooxygenase reactions.
abstract: Cytochrome P450 can undergo inactivation following monooxygenase reactions in liver microsomes of untreated, phenobarbital and 3-methylcholanthrene-treated rats and rabbits. The acceleration of cytochrome P450 loss in the presence of catalase inhibitors (sodium azide, hydroxylamine) indicates that hydrogen peroxide is involved in hemoprotein degradation. It was revealed that cytochrome P450 is inactivated mainly by H2O2 formed through peroxy complex breakdown, whereas H2O2 formed via the dismutation of superoxide anions produces a slight inactivating effect. The hydrogen peroxide added outside or formed by a glucose-glucose oxidase system has less of an inactivating effect than H2O2 produced within the cytochrome P450 active center. Self-inactivation of cytochrome P450 during oxygenase reactions is highly specific. Other components of the monooxygenase system, such as cytochrome b5, NADH- and NADPH-specific flavoproteins, undergo no inactivation. The alterations in phospholipid content and in the rate of lipid peroxidation were not observed as well. The inactivation of cytochrome P450 by H2O2 is the result of heme loss or destruction without cytochrome P420 formation. Such a mechanism operates with different substrates and cytochrome P450 species catalyzing the partially coupled monooxygenase reactions.
authors.affiliation: Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow.
authors.forename: I I
authors.initials: II
authors.lastname: Karuzina
authors.forename: A I
authors.initials: AI
authors.lastname: Archakov
mesh_terms: D000818:Animals; D002374:Catalase / Q000037:antagonists & inhibitors*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000737:chemistry*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D011817:Rabbits
chemical_list: D003577:Cytochrome P-450 Enzyme System; D006861:Hydrogen Peroxide; D002374:Catalase