title: The mechanism of hydroperoxide-dependent reactions with participation of cytochrome P-450.
abstract: Cytochrome P-450 destruction kinetics by cumene hydroperoxide (CHP) has been studied at 25 degrees C in phosphate buffer, pH 7.25-7.50, in various systems: intact and induced rat or rabbit microsomes, highly purified LM2- and LM2- and LM4-forms of cytochrome P-450 from rabbit liver microsomes. The destruction kinetics is characterized by three phases in all systems. The CHP-influenced cytochrome P-450 destruction is a radical chain process with linear termination of the chains. The acidic phospholipids, phosphatidylserine and phosphatidylinositol and total microsomal phospholipids containing the acidic lipid components activate cytochrome P-450 in the hydroxylation of aniline and naphthalene by CHP. Phosphatidylcholine and sphingomyelin have no effect upon the cytochrome P-450 activity in the type I and II substrates oxidation by CHP. The phase transitions of the microsomal phospholipids influence the interaction of cytochrome P-450 with its reductase, altering the activation energy of type I substrates oxidation. The type II substrate oxidation is not affected by phase transitions in the full microsomal hydroxylating system.
mesh_terms: D000818:Animals; D001555:Benzene Derivatives; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010084:Oxidation-Reduction; D010545:Peroxides; D010634:Phenobarbital / Q000494:pharmacology; D010743:Phospholipids / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013379:Substrate Specificity
chemical_list: D001555:Benzene Derivatives; D010545:Peroxides; D010743:Phospholipids; D003577:Cytochrome P-450 Enzyme System; C007164:cumene hydroperoxide; D010634:Phenobarbital