Cytochrome P450 kinetic parameters

Based on in vitro studies of hepatic microsomal-catalysed oxidative reactions, using liver specimens from a variety of animal species including man, and marker substrates for the various reactions, it can be concluded that neither the measured levels of cytochrome P450 and cytochrome nor the activity of NADPH-cytochrome c reductase accounts for species variations in the capacity of oxidative reactions (McManus and Ilett, 1976 Dalvi et al., 1987 Souhaili-El-Amri et al., 1986). However, species variations could be attributed to differences in values of the kinetic parameters (Michaelis constant, Km, and the maximum reaction velocity, Vmax) associated with individual reactions. 

Similar to the techniques used for calculation of chemical disposition parameters, in vivo biotransformation kinetic parameters of a substrate can be estimated from in vitro systems such as microsomes, freshly isolated hepatocytes, fiver slices, and isolated perfused livers (24). Intrinsic clearance or Michaelis-Menten parameters for the whole liver can also be obtained by scaling in vitro parameters based on the cytochrome P450 enzyme content (25-27). These parameters can also be estimated from in vitro data obtained from recombinant human CYP systems, and also through allometric scaling of clearance estimates from animal PBPK models. 

Wang Q, Sheng X, Homer JH, Newcomb M (2009) Quantitative production of Compound I Horn a cytochrome P450 enzyme at low temperatures. Kinetics, activation parameters, and kinetic isotope effects for oxidation of benzyl alcohol. J Am Chem Soc 131 10629-10636... 

In another study by Godin et al. (2007), the rat and human CYP450 isoforms and rat serum esterase that metabolized deltamethrin and esfenvalerate were identified. Table 12 gives the Vmax and kinetic parameters for the metabolism of deltamethrin and esfenvalerate by rat and human recombinant cytochrome P450s. 

Table 12 Kinetic parameters for deltamethiin and esfenvaleiate metabolism by rat and human cytochrome P450s...

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