Protein oxidation by the cytochrome P450 mixed-function oxidation system

This mini-review summarizes results of studies on the oxidation of proteins and low-density lipoprotein (LDL) by various mixed-function oxidation (MFO) systems. Oxidation of LDL by the O₂/FeCl₃/H₂O₂/ascorbate MFO system is dependent on all four components and is much greater when reactions are carried out in the presence of a physiological bicarbonate/CO₂ buffer system as compared to phosphate buffer. However, FeCl₃ in this system could be replaced by hemin or the heme-containing protein, hemoglobin, or cytochrome c. Oxidation of LDL by the O₂/cytochrome P450 cytochrome c reductase/NADPH/FeCl₃ MFO system is only slightly higher (25%) in the bicarbonate/CO₂ buffer as compared to phosphate buffer, but is dependent on all components except FeCl₃. Omission of FeCl₃ led to a 60% loss of activity. These results suggest that peroxymonobicarbonate and/or free radical derivatives of bicarbonate ion and/or CO₂ might contribute to LDL oxidation by these MFO systems.