The Ferrous-Dioxygen Complex

The properties of oxy-P450 were first characterized in P450 CYPlOl and other isozymes using optical absorption resonance Raman - and Mossbauer spec- 

The absorption spectra and autoxidation properties of oxygen complexes for several cytochromes P450 °- -, and related 

Oxygen is found to be coordinated in the bent end-on mode (with a Fe-O-0 angle of 136°). This structure provides a starting point for the formation of the end-on bound peroxo-ferric complex, which is the first of three unstable and highly reactive intermediates in the P450 catalytic cycle. 

Reduction of Oxy-Ferrous P450 and Formation of Peroxo-Ferric Complexes Properties, Stability, and Spectroscopy 

The stability of iron-peroxo complexes is marginal in heme systems in the presence of a strong proximal ligand (His, Cys, or Tyr), and the aqueous solution at a near-neutral pH. The numerous attempts to isolate such complexes obtained in reactions of hydrogen peroxide with P450 at ambient conditions have failed because of the inherent low stability and fast conversion to ferryl-oxo species with 0-0 bond scission There have been successful isolations of the ferriheme-peroxide complex in myoglobin, however .  

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Estabrook, R.W., Hildebrandt, A.G., Baron, J., Netter, K.J. and Leibman, K. (1971) A new spectral intermediate associated with cytochrome P-450 function in liver microsomes. Biochemical and Biophysical Research Communications, 42 (1), 132-139. Pompon, D. and Coon, M.J. (1984) On the mechanism of action of cytochrome P-450. Oxidation and reduction of the ferrous dioxygen complex of liver microsomal cytochrome P-450 by cytochrome b5. Journal of Biological Chemistry, 259 (24), 15377-15385. Hildebrandt, A. and Estabrook, R.W. (1971) Evidence for the participation of cytochrome b 5 in hepatic microsomal mixed-function oxidation reactions. Archives of Biochemistry and Biophysics, 143 (1), 66-79. 

Pompon D, Coon MJ (1984) On the mechanism of action of cytochrome P-450. Oxidation and reduction of the ferrous dioxygen complex of liver microsomal cytochrome P-450 by cytochrome bj. J Biol Chem 259 15377-15385... 

Oxygen Binding and the Structure of the Ferrous Dioxygen Complex... 

E° = —196 mV) to the ferric P450CAM heme iron to produce the ferrous state of the protein, 3. Dioxygen binds to the ferrous heme iron to form the ferrous oxy complex, 4a/4b, whose valence structure can be presented either as the ferrous-02, 4a, or as the ferric superoxide, 4b, complex. Addition of carbon monoxide to 3 yields a ferrous carbon monoxide adduct, 5, with its characteristic absorbance peak at 450 nm [37],... 

Ferrous porphyrin is a good dioxygen binder, and this leads to the binding of molecular oxygen to produce the LS ferrous-dioxygen complex,... 

How does nature prevent the release of hydrogen peroxide during the cytochrome oxidase-mediated four-electron reduction of dioxygen It would appear that cytochrome oxidase behaves in the same manner as other heme proteins which utilize hydrogen peroxide, such as catalase and peroxidase (vide infra), in that once a ferric peroxide complex is formed the oxygen-oxygen bond is broken with the release of water and the formation of an oxo iron(IV) complex which is subsequently reduced to the ferrous aquo state (12). Indeed, this same sequence of events accounts for the means by which oxygen is activated by cytochromes P-450. 

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