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Enzyme Kinetics of Oxidative Metabolism: Cytochromes P450

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Enzyme Kinetics in Drug Metabolism

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1113))

Abstract

The cytochrome P450 enzymes (CYPs) are the most important enzymes in the oxidative metabolism of hydrophobic drugs and other foreign compounds (xenobiotics). 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 inhibition kinetics (see Chapter 3). Interactions between substrates include competitive inhibition, noncompetitive inhibition, mixed inhibition, partial inhibition, activation, and activation followed by inhibition (see Chapter 4). Models and equations that can result in these kinetic profiles will be presented and discussed.

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Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA

    Ken Korzekwa

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  1. Ken Korzekwa
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Editor information

Editors and Affiliations

  1. Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania, USA

    Swati Nagar

  2. Novartis Inst. for BioMedical Research, Cambridge, Massachusetts, USA

    Upendra A. Argikar

  3. Drug Metabolism, Boehringer Ingelheim, Ridgefield, Connecticut, USA

    Donald J. Tweedie

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Korzekwa, K. (2014). Enzyme Kinetics of Oxidative Metabolism: Cytochromes P450. In: Nagar, S., Argikar, U., Tweedie, D. (eds) Enzyme Kinetics in Drug Metabolism. Methods in Molecular Biology, vol 1113. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-758-7_8

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  • DOI: https://doi.org/10.1007/978-1-62703-758-7_8

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-757-0

  • Online ISBN: 978-1-62703-758-7

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