Co-oxidation of xenobiotics: lipid peroxyl derivatives as mediators of metabolism.
Systems which carry out peroxyl-dependent oxidations can serve as activation systems for carcinogenic compounds. Some function via classical peroxidase reactions in which an enzyme-derived oxidant performs the electron abstraction from or oxygen donation to the oxidizable substrate. This mechanism applies to the peroxidative activation of aromatic amines and of the phenolic compound diethylstilbestrol. These classical peroxidase reactions may be initiated by hydrogen peroxide or by organic peroxides, including lipid hydroperoxides. A different mechanism is involved in the oxygenation of polycyclic aromatic hydrocarbons and of aflatoxin B1. In these cases the oxidant is a peroxyl radical, and the reaction occurs by the direct, non-enzymatic interaction of the peroxyl radical and the oxidizable substrate. Most peroxyl radicals in biological systems are lipid-derived. The key reaction which distinguishes the peroxyl radical-dependent oxidations from the classical peroxidase reactions is the ability of the former to epoxidize activated carbon-carbon double bonds. The epoxidation of benzo[a]pyrene derivatives has been studied extensively in subcellular and whole cell and tissue systems, and is discussed as a model for this class of reaction. Determining the generality of this activation path and its role in vivo present the major questions to be answered in regard to the importance of these reactions in chemical carcinogenesis.
Reed
G A
GA
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
D001711:Biotransformation; D008054:Lipid Peroxides / Q000502:physiology*; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000378:metabolism*; D011083:Polycyclic Compounds / Q000378:metabolism
D008054:Lipid Peroxides; D011083:Polycyclic Compounds; D010544:Peroxidases