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Multienzyme Kinetics and Sequential Metabolism

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Enzyme Kinetics in Drug Metabolism

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

Abstract

Enzymes are the catalysts of biological systems and are extremely efficient. A typical enzyme accelerates the rate of a reaction by factors of at least a million compared to the rate of the same reaction in the absence of the enzyme. In contrast to traditional catalytic enzymes, the family of cytochrome P450 (CYP) enzymes are catalytically promiscuous, and thus they possess remarkable versatility in substrates. The great diversity of reactions catalyzed by CYP enzymes appears to be based on two unique properties of these heme proteins, the ability of their iron to exist under multiple oxidation states with different reactivities and a flexible active site that can accommodate a wide variety of substrates. Herein is a discussion of two distinct types of kinetics observed with CYP enzymes. The first example is of CYP complex kinetic profiles when multiple CYP enzymes form the sample product. The second is sequential metabolism, in other words, the formation of multiple products from one CYP enzyme. Given the degree of CYP enzyme promiscuity, it is hardly surprising that there is also a high degree of complex kinetic profiles generated during the catalytic cycle.

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Author information

Authors and Affiliations

  1. Pharmacokinetics and Drug Metabolism Department, Amgen Inc., Seattle, WA, USA

    Larry C. Wienkers & Brooke Rock

Authors
  1. Larry C. Wienkers
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  2. Brooke Rock
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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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Wienkers, L.C., Rock, B. (2014). Multienzyme Kinetics and Sequential Metabolism. 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_6

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  • DOI: https://doi.org/10.1007/978-1-62703-758-7_6

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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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