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 (Fe(III)MP-8) and manganese-containing microperoxidase-8 (Mn(III)MP-8) with H(2)O(2). 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[double bond]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, H(2)O plays a decisive role, at least in some cytochromes P450, in the removal of halogens, avoiding the production of compounds hazardous to the organism.
Veeger
Cees
C
Laboratory of Biochemistry, Wageningen University, Dreijenlaan 3, 6703 HA Wageningen, The Netherlands. cees.veeger@planet.nl
D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism; D003574:Cytochrome c Group / Q000737:chemistry / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry; D007501:Iron / Q000737:chemistry*; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry; D010544:Peroxidases / Q000737:chemistry* / Q000378:metabolism
D003574:Cytochrome c Group; D009842:Oligopeptides; D003577:Cytochrome P-450 Enzyme System; D006861:Hydrogen Peroxide; D007501:Iron; D010544:Peroxidases; C021799:microperoxidase; D010100:Oxygen