Model studies in cytochrome P-450-mediated toxicity of halogenated compounds: radical processes involving iron porphyrins.
Haloalkane toxicity originates from attack on biological targets by reactive intermediates derived from haloalkane metabolism by a hemoprotein, cytochrome P-450. Carbon-centered radicals and their peroxyl derivatives are most likely involved. The reactions of iron porphyrin--a model for cytochrome P-450--with various carbon-centered and peroxyl radicals generated by pulse radiolysis are examined. Competition between iron porphyrin and unsaturated fatty acids for attack by peroxyl radicals is pointed out. These kinetic data are used to derive a model for toxicity of haloalkanes with particular attention to carbon tetrachloride and halothane. The importance of local oxygen concentration and structural arrangement of fatty acids around cytochrome P-450 is emphasized.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005609:Free Radicals; D006846:Hydrocarbons, Halogenated / Q000378:metabolism / Q000633:toxicity*; D006878:Hydroxides; D017665:Hydroxyl Radical; D008954:Models, Biological; D011166:Porphyrins / Q000378:metabolism*; D013329:Structure-Activity Relationship
D005227:Fatty Acids; D005609:Free Radicals; D006846:Hydrocarbons, Halogenated; D006878:Hydroxides; D011166:Porphyrins; D017665:Hydroxyl Radical; D003577:Cytochrome P-450 Enzyme System