H₂O₂ activation and mediation

            An important function of hemes are in generating and mediating the effects of reactive oxygen species, ROS. These ROS, like peroxide and superoxide, are part of the body's defense mechanism, and also generated during respiration. They are implicated in disease, cancer and aging-- and are counteracted by the anti-oxidants you have heard so much about. Heme proteins are also efficient anti-oxidants, controling and using the ROS for a variety of cellular functions. 

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Horseradish Peroxidase contains one heme site which is bound to the protein through a proximal pocket histidine, similar to myoglobin and hemoglobin. There is also a distal histidine which H-bonds to Fe-bound peroxide. It is involved in heterolytic cleavage of the O-O bond, as illustrated in the cartoon below. This results in an O=Fe(IV) and a cation- radical formed on the porphyrin itself.

Cytochrome C Peroxidase is an interesting case in that the radical does not stay on the porphyrin, but migrates to a close by tryptophan. It's redox partner is cytochrome c, and its thought the trp radical holds the radical equivalent closer to the cytochrome c binding surface for more efficient electron transfer.

Cytochrome C Peroxidase is over twice the size of myglobin, ca 50 kD, and most peroxidases are similarly sized. In general, the heme sites in peroxidases are protected, with solvent access only to one side of the heme. Peroxide can get to the Fe site, but organic substrates can only bind near the heme edge. Thus, peroxidases function as outer-sphere oxidants of organic molecules.