Oxygen activation by cytochrome

Yeom, H. Y., and Sligar, S. G. 1997 Oxygen activation by cytochrome P450(BM-3) Effects of mutating an active site acidic residue. Arch. Biochem. Biophys., 337, 209-216. 

Coon, M.J., White, R.E., and Blake, R.C. (1981) Oxygen activation by cytochrome P450, in King, T.E. (ed.) Oxidases and related systems, 1, University Park Press, Baltimore, pp. 93-118. 

Aikens, J. and S.G. Sligar (1994). Kinetic solvent isotope effects during oxygen activation by cytochrome P-450cam. J. Am. Chem. Soc. 116, 1143-1144. 

Shimada, H., Y. Watanabe, M. Imai, R. Makino, H. Koga, T. Horiuchi et al. (1991). The role of threonine 252 in the oxygen activation by cytochrome P-450cam Mechanistic studies by site-directed mutagenesis. In L.I. Simandi (ed.). Dioxygen Activation and Homogeneous Catalytic Oxidation. Elsevier Science Publishers, Amsterdam, pp. 3136-319. 

White RE, Coon MJ. Oxygen activation by cytochrome P450. Ann Rev Biochem 1980 49 315-356. 

Zhao B, Guengerich FP, Voehler M, Waterman MR (2005) Role of active site water molecules and substrate hydroxyl groups in oxygen activation by cytochrome P450 158A2 a new mechanism of proton transfer. J Biol Chem 280 42188 2197... 

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. 

Proposed model for oxygen activation in cytochrome P450. Reduction by a single electron enables the ferrous iron to bind oxygen. Addition of a second electron generates an iron peroxide heme, which then cleaves to form water and an electrophilic perferryl species. 

Makris TM, Davydov R, Denisov IG, et al. Mechanistic enzymology of oxygen activation by the cytochromes p450. Drug Metab Rev 2002 34 691-708. 

Such reactions are interesting as models for oxygen atom transfer in mechanisms of dioxygen activation by cytochrome P450 enzyme systems (49, 50, 51). 

J. T. Groves, Y. Watanabe, Oxygen activation by metalloporphyrins related to peroxidase and cytochrome P-450. Direct observation of the oxygen-oxygen bond cleavage step, /. Am. Chem. Soc. 108 (1986) 7834. 

The known functions of the heme proteins depend critically on the presence of iron. It is a reasonable hypothesis to consider that inorganic iron complexes may have been the evolutionary precursors of the heme proteins, since all of the catalytic activity of these heme proteins can be observed, albeit weakly in simpler iron complexes 169, 170). The most important of these catalytic activities are (a) the use of cytochromes as electron carriers in the coupling of the oxidation of various substrates to an oxidant, usually oxygen (6) the activation of oxygen (usually by cytochrome oxidase) to accept electrons (c) the activation of H2O2 to oxidize a substrate or to decompose it to H2O and Oj (d) the formation of reversible complexes with Oa as in hemoglobin. These activities of inorganic iron complexes will now be discussed in turn. 

Activation of oxygen by cytochrome P-450 and other hemoproteins. D. I. Metelitsa, Russ. Chem. Rev. (Engl. Transl), 1982, 51,1042-1059 (184). 

---