Cytochrome oxygen activation model

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. 

The focus of this chapter is the reaction site of oxygenases (hemo-proteins) having heme as the prosthetic group. We discuss the oxygen activation in tryptophan pyrrolase (TPO) and cytochrome P-450 based on our experimental results using iron-porphyrin complexes as the model for the active site of these enzymes. 

Naruta, Y., Sasaki, T, Tani, F, Tachi, Y., Kawato, N., and Nakamura N (2001) Heme-Cu complexes as oxygen-activating functional models for the active site of cytochrome c oxidase, J. Inorg. Biochem. 83, 239-46. 

Oxygen reduction Models have been created for cytochrome oxidase, which have provided insights into the oxygen activation and reduction mechanism. 

In this model system, as contrasted with the simple ferric ion reductase activity of the flavoprotein (38S), the metal is not the ultimate electron acceptor but presumably serves the dual role of oxygen activation and electron carrier. The reaction may involve superoxide anion since it is inhibited by superoxide dismutase (erthrocuprein) (394). Xanthine plus xanthine oxidase can also serve as electron donor, and this latter model system is also inhibited by superoxide dismutase (5P5). Superoxide dismutase also inhibits the menadione-mediated NADPH oxidase activity of NADPH-cytochrome P-450 (396) as well as the reconstituted benz-phetamine bydroxylation system (397). The involvement of NADPH-cytochrome P-450 reductase in microsomal lipid peroxidation has been confirmed by the demonstration that the reaction in microsomes is totally inhibited by antibody to tbe purified reductase (374). It has been suggested that lipid peroxidation by microsomes requires another component, in addition to the reductase, which takes the place of the ferric ion chelate in the model system (57. ). 

A few systems mimicking the oxygen activation and transfer step of cytochrome P450 in model vesicular membranes have recently been described. 

Transition metal hydroperoxo species are well established as important intermediates in the oxidation of hydrocarbons (8,70,71). As they relate to the active oxygenating reagent in cytochrome P-450 monooxygenase, (porphyrin)M-OOR complexes have come under recent scmtiny because of their importance in the process of (poiphyrin)M=0 formation via 0-0 cleavage processes (72-74). In copper biochemistry, a hydroperoxo copper species has been hypothesized as an important intermediate in the catalytic reaction of the copper monooxygenase, dopamine P-hydroxylase (75,76). A Cu-OOH moiety has also been proposed to be involved in the disproportionation of superoxide mediated by the copper-zinc superoxide dismutase (77-78). Thus, model Cun-OOR complexes may be of... 

Cavalieri E.L. and Rogan, E.G. (2002) Fluoro substitution of carcinogenic aromatic hydrocarbons models for understanding mechanisms of metabolic activation and of oxygen transfer catalyzed by cytochrome P450, in The Handbook of Environmental Chemistry, Vol. 3,... 

These superoxo complexes are relevant models for the naturally occurring oxygen carriers hemoglobin and myoglobin, which contain ferroprotoporphyrin IX as an active center in which the sixth axial postion is occupied by the imidazole moiety of histidine.17 They also intervene as primary oxygen adducts in enzymatic cytochrome P-450 oxygenases.18... 

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

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