NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology

David S Riddick, Xinxin Ding, C Roland Wolf, Todd D Porter, Amit V Pandey, Qing-Yu Zhang, Jun Gu, Robert D Finn, Sebastien Ronseaux, Lesley A McLaughlin, Colin J Henderson, Ling Zou, Christa E Flück

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    Abstract

    This is a report on a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 2012 meeting in San Diego, California, on April 25, 2012. The symposium speakers summarized and critically evaluated our current understanding of the physiologic, pharmacological, and toxicological roles of NADPH-cytochrome P450 oxidoreductase (POR), a flavoprotein involved in electron transfer to microsomal cytochromes P450 (P450), cytochrome b(5), squalene mono-oxygenase, and heme oxygenase. Considerable insight has been derived from the development and characterization of mouse models with conditional Por deletion in particular tissues or partial suppression of POR expression in all tissues. Additional mouse models with global or conditional hepatic deletion of cytochrome b(5) are helping to clarify the P450 isoform- and substrate-specific influences of cytochrome b(5) on P450 electron transfer and catalytic function. This symposium also considered studies using siRNA to suppress POR expression in a hepatoma cell-culture model to explore the basis of the hepatic lipidosis phenotype observed in mice with conditional deletion of Por in liver. The symposium concluded with a strong translational perspective, relating the basic science of human POR structure and function to the impacts of POR genetic variation on human drug and steroid metabolism.
    Original languageEnglish
    Pages (from-to)12-23
    Number of pages12
    JournalDrug Metabolism and Disposition
    Volume41
    Issue number1
    DOIs
    Publication statusPublished - Jan 2013

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    Keywords

    • Alleles
    • Animals
    • Cytochromes b5
    • Mice
    • Mice, Knockout
    • Microsomes, Liver
    • NADPH-Ferrihemoprotein Reductase
    • Pharmaceutical Preparations
    • Tumor Cells, Cultured

    Cite this

    Riddick, D. S., Ding, X., Wolf, C. R., Porter, T. D., Pandey, A. V., Zhang, Q-Y., Gu, J., Finn, R. D., Ronseaux, S., McLaughlin, L. A., Henderson, C. J., Zou, L., & Flück, C. E. (2013). NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology. Drug Metabolism and Disposition, 41(1), 12-23. https://doi.org/10.1124/dmd.112.048991