Download Cytochromes P450: Structure, Function and Mechanism (Taylor by David F.V. Lewis PDF

By David F.V. Lewis

This consultant to the constitution, functionality and mechanism of the cytochromes P450 specializes in the position of P450s in xenobiotic metabolism and toxicity. color illustrations exhibit how modelling of P450s can rationalize their substrate specificity for the metabolism of either endogenous and exogenous chemical substances.

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Additional info for Cytochromes P450: Structure, Function and Mechanism (Taylor & Francis Series in Pharmaceutical Sciences)

Sample text

1993) but also the particular characteristics of the heme environment that are largely controlled by the apoprotein. 3 Vibrational spectroscopy Both infra-red (IR) and resonance Raman (RR) spectroscopy have been employed to study cytochromes P450 and related hemoproteins, with RR being the more commonly used, as far as P450 is concerned, because potentially more useful information can be obtained. In particular, vibrational and vibronic transitions associated with the porphyrin ring environment can be investigated by RR spectroscopy (Spiro, 1983; Ruckpaul and Rein, 1984; Lewis, 1986; Hildebrandt, 1992).

20). e. 20). It is also found that the binding of substrates or inhibitors to P450s will bring about a change in the proton NMR signals indicative of a movement of solvent water away from the heme iron to a distance of up to about 7 Å (Griffin and Peterson, 1975). In addition to solvent water proton relaxation, substrate and inhibitor interactions within the active sites of various P450s can be studied via proton NMR by investigating the effect of the heme iron on relaxation times (Weiner, 1986).

Due to the thermal mixing of spin states at room temperatures, cryogenic temperatures are required for the detailed observation of both low- and high-spin Fe3+ ESR spectra; in particular, liquid helium temperatures (~ 4 K) are employed for the visualization of the high-spin signals. This is due to the fact that population of the MS±½ state falls exponentially with rise in temperature, thus bringing about dramatic reduction in the intensity of the resonant signals produced in the ESR spectrum. 0, respectively (Lewis, 1986).

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