Enzyme Kinetics of Oxidative Metabolism—Cytochromes P450

The cytochrome P450 enzymes (CYPs) are the most important enzymes in the oxidative metabolism of hydrophobic drugs and other foreign compounds (xenobioticsXenobiotics). The versatility of these enzymes results in some unusual kinetic properties, stemming from the simultaneous interaction of multiple substrates with the CYP active site. Often, the CYPs display kinetics that deviate from standard hyperbolic saturation or inhibition kinetics. Non-Michaelis-Menten or “atypical” saturation kinetics include sigmoidal, biphasic, and substrate inhibitionInhibitionsubstrate inhibition kinetics (see Chapter 2 ). Interactions between substrates include competitive inhibitionInhibitioncompetitive inhibition, noncompetitive inhibition, mixed inhibition, partialInhibitionpartial inhibition, activationActivation, and activationActivation followed by inhibition (see Chapters 4 and 6 ). Models and equations that can result in these kinetic profiles will be presented and discussed.