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    Cytochrome P450 and flavin-containing monooxygenase families: Age-dependent differences in expression and functional activity

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    Issue Date
    2017-11-01
    Author
    Zane, Nicole R.
    Chen, Yao
    Wang, Michael Zhuo
    Thakker, Dhiren R.
    Publisher
    Springer Nature
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Rights
    Copyright © 2018 International Pediatric Research Foundation, Inc.
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    Abstract
    Background Age-dependent differences in pharmacokinetics exist for metabolically cleared medications. Differential contributions in the cytochrome P450 3A (CYP3A), CYP2C, and flavin-containing monooxygenases (FMOs) families have an important role in the metabolic clearance of a large number of drugs administered to children.

    Methods Unlike previous semiquantitative characterization of age-dependent changes in the expression of genes and proteins (western blot analysis), this study quantifies both gene and absolute protein expression in the same fetal, pediatric, and adult hepatic tissue. Expression was then correlated with the corresponding functional activities in the same samples.

    Results CYP3A and FMO families showed a distinct switch from fetal (CYP3A7 and FMO1) to adult isoforms (CYP3A4 and FMO3) at birth, whereas CYP2C9 showed a linear maturation from birth into adulthood. In contrast, analysis of CYP2C19 revealed higher expression and catalytic efficiency in pediatric samples compared with that in fetal and adult samples. Further, CYP3A and FMO enzymes exhibited an unexpectedly higher functional activity in fetal samples not entirely explained by protein expression.

    Conclusion These surprising findings suggest that CYP and FMO enzymes may encounter development-related differences in their microenvironments that can influence the enzyme activity in addition to protein expression levels.
    URI
    http://hdl.handle.net/1808/32227
    DOI
    https://doi.org/10.1038/pr.2017.226
    Collections
    • Pharmaceutical Chemistry Scholarly Works [354]
    Citation
    Zane, N. R., Chen, Y., Wang, M. Z., & Thakker, D. R. (2018). Cytochrome P450 and flavin-containing monooxygenase families: age-dependent differences in expression and functional activity. Pediatric research, 83(2), 527–535. https://doi.org/10.1038/pr.2017.226

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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