Ipso-Substitution by Cytochrome P450 with Conversion of p-Hydroxybenzene Derivatives to Hydroquinone: Evidence for Hydroperoxo-Iron As the Active Oxygen Species

摘要: Abstract Evidence for multiple functional active oxidants in cytochrome P450-catalyzed reactions was previously obtained this laboratory with mutants which proton delivery perturbed by replacement of the highly conserved threonine residue site alanine, thus apparently interfering conversion peroxo-iron to hydroperoxo-iron and latter oxenoid-iron species. These enzymes have now been employed examine reaction P450 liver microsomes is known effect ipso -substitution, elimination p -substituents phenols yield hydroquinone. As shown purified NH 2 -truncated cytochromes a reconstituted enzyme system, exhibits an absolute requirement NADPH–cytochrome reductase. Under optimal conditions truncated 2E1 10 -substituted examined. Of particular interest, corresponding threonine-303 replaced alanine from 1.5- 50-fold higher activity p- chloro, -bromo, -nitro, -cyano, -hydroxymethyl, -formyl, -acetyl derivatives, -benzoyl, -methyl, - t -butyl compounds catalyzed mutant only. The results implicate species as electrophilic oxidant aromatic -substitution.