The involvement of free radicals in the mechanisms of monooxygenases.
The occurrence of free radicals in the mechanisms of monooxygenases reflects the chemistry of dioxygen and the inertness of typical substrates. Thus, oxidation of such substrates requires attack by reduced dioxygen-derived free radicals. Consequently, a molecule of NAD(P)H must be invested for each substrate molecule oxidized. Furthermore, since free radicals are difficult to control, deviations from the intended reaction course are frequent. These considerations are illustrated by examination of the generation and fate of enzyme- and substrate-derived free radicals at various stages in the catalytic cycles of two monooxygenases important in xenobiotic biotransformation, dopamine beta-hydroxylase and cytochrome P-450.
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Department of Drug Metabolism, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D006899:Mixed Function Oxygenases / Q000378:metabolism*
D005609:Free Radicals; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D004299:Dopamine beta-Hydroxylase