Catalytic cycle, P450 monooxygenases

However, most of the debate in this area has been over the mechanism of epoxidation by cytochrome P450 (c-P450) and its analogs. C-P450 is a monooxygenase whose active center is an iron(III) porphyrin136 its catalytic cycle is shown in Scheme 53137. 

The catalytic cycle of cytochrome P-450, typical of monooxygenases, is presented in Figure 13.12 (Johnston, Ouellet, Podust, Ortiz de Montellano, 2011). This substrate hydroxylation reaction is mediated by the Compound I -like ferryl species formed during the catalytic turnover of P450 enzymes. The Fe(lV) haem iron... 

FIGURE 32.2 Catalytic cycle of cytochrome P450 associated with monooxygenase reactions. [Fe ] = ferricytochrome P450 hs = high spin Is = low spin [Fe ] = ferrocytochrome P450 Fpi = flavoprotein 1 = NADPH-cytochrome P450 reductase Fp2 = NADH-cytochrome 65 reductase cyt 65 = cytochrome 65 XH = substrate (modified from ). 

FIGURE 33.2 Catalytic cycle of cytochrome P450 (CYP) monooxygenase. 

Figure 13.2. Catalytic cycle of cytochrome P450 associated with monooxygenase reactions. (Fe " ), ferricytochrome P450 hs, high spin Is, low spin (Fe " ), ferrocytochrome P450 Fpi, flavoprotein 1-NAJDPH-cytochrome P450 reductase Fpg, NADH-cytochrome bg reductase cyt b cytochrome b, XH, substrate (modified from Ref 6).

Most monooxygenases that are ubiquitous in living organisms contain an hemeprotein called cytochrome P450. The active oxygen species involved in the catalytic cycle of these enzymes seems to be an oxyferryl complex of the Fe(V)=0... 

Scheme 12.1 The catalytic cycle of cytochrome P450 monooxygenases (reproduced from Ref. [44],...

Scheme 5.2 Catalytic cycle of P450 monooxygenases. In P450, the heme group is bound to the protein backbone via cysteine (Cys-S-). RH indicates the substrate. Numbering indicates different heme iron species (for details refer to main text).

Cytochrome P450 monooxygenases contain a heme prosthetic group and require electrons for their activity. In the P450 catalytic cycle, two consecutive electron-transfer... 

The broad application of cytochrome P450 monooxygenases for synthetic purposes is still hampered by their comparably low catalytic rates and their usually rather limited stability, especially in isolated form, because of the possible formation of reactive oxygen species during the catalytic cycle (Scheme 36.17). Nevertheless, industrial applications of CYPs in the syntheses of certain drugs, e.g., the stereoselective hydroxylation of steroids or the oxidation of compactin 43 to pravastatin 44, a potent cholesterol-lowering agent, have already been reported (Scheme 36.18). ... 

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