Does P450-type catalysis proceed through a peroxo-iron intermediate? A review of studies with microperoxidase

Recent stopped-flow kinetics demonstrated the existence of an intermediate before the occurrence of the final product of the reaction of both iron-containing microperoxidase-8 ((FeMP)-M-III-8) and manganese-containing microperoxidase-8 ((MnMP)-M-III-8) with H2O2. The intermediate was assigned to be (hydro)peroxo-iron. With both mini-catalysts the final state obtained after 30-40 ms showed a resemblance to PorM(IV)MP-8=O(R+.); (R+.) is a radical located at the peptide. Quantum mechanical calculations indicate that hydroperoxo-iron is inactive as a catalytic intermediate in cytochrome P450 (P450)-type catalysis. Instead, the calculations suggest that peroxo-iron acts as the catalytic intermediate in P450-type catalysis. In addition, the calculations demonstrate that, although less likely, the possibility that oxenoid-iron acts as a catalytic intermediate in P450 catalysis cannot be fully excluded. An interesting aspect of the reactions catalysed by MP-8 is the possibility that, in view of the reversibility of the reactions between (hydro)peroxo-iron and oxenoid-iron, H2O plays a decisive role, at least in some cytochromes P450, in the removal of halogens, avoiding the production of compounds hazardous to the organism. (C) 2002 Elsevier Science Inc. All rights reserved.