The lipid peroxidation model for halogenated hydrocarbon toxicity. Kinetics of peroxyl radical processes involving fatty acids and Fe(III) porphyrins.
The toxicity of halogenated alkanes originates from their metabolism by cytochrome P-450 which leads to the formation of reactive intermediates. In particular, peroxyl radicals derived from the halogenated compounds are believed to induce peroxidative chain degradation of lipids. To examine this hypothesis, radical reactions in a system involving FeIII-deuteroporphyrin as a model of cytochrome P-450, fatty acids or cholesterol, and carbon tetrachloride or the anesthetic agent halothane are studied by means of pulse radiolysis. It is shown that haloperoxyl radicals react with the fatty acids in competition with their reaction with the ferriporphyrin. Moreover, the secondary fatty acid peroxyl radicals also react efficiently with the porphyrin. A model for halogenated alkane toxicity is discussed in terms of these new findings. The importance of local oxygen concentration and structural arrangement of fatty acids around cytochrome P-450 are emphasized.
D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005290:Ferric Compounds / Q000378:metabolism; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism*; D008665:Metalloporphyrins / Q000378:metabolism*; D008954:Models, Biological; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism*
D005230:Fatty Acids, Nonesterified; D005290:Ferric Compounds; D006846:Hydrocarbons, Halogenated; D008054:Lipid Peroxides; D008665:Metalloporphyrins; D013481:Superoxides; D003577:Cytochrome P-450 Enzyme System