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dc.contributor.authorZane, Nicole R.
dc.contributor.authorChen, Yao
dc.contributor.authorWang, Michael Zhuo
dc.contributor.authorThakker, Dhiren R.
dc.identifier.citationZane, 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.
dc.description.abstractBackground 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.
dc.publisherSpringer Natureen_US
dc.rightsCopyright © 2018 International Pediatric Research Foundation, Inc.en_US
dc.titleCytochrome P450 and flavin-containing monooxygenase families: Age-dependent differences in expression and functional activityen_US
kusw.kuauthorChen, Yao
kusw.kuauthorWang, Michael Zhuo
kusw.kudepartmentPharmaceutical Chemistryen_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

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