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• W2014232034 endingPage "1750" @default.
• W2014232034 startingPage "1736" @default.
• W2014232034 abstract "Cellular production of flavonoid glucuronides requires the action of both UDP-glucuronosyltransferases (UGT) and efflux transporters since glucuronides are too hydrophilic to diffuse across the cellular membrane. We determined the kinetics of efflux of 13 flavonoid glucuronides using the newly developed HeLa-UGT1A9 cells and correlated them with kinetic parameters derived using expressed UGT1A9. The results indicated that, among the seven monohydroxylflavones (HFs), there was moderately good correlation (r2 ≥ 0.65) between the fraction metabolized (fmet) derived from HeLa-UGT1A9 cells and CLint derived from the UGT1A9-mediated metabolism. However, there was weak or no correlation between these two parameters for six dihydroxylflavones (DHFs). Furthermore, there was weak or no correlation between various kinetic parameters (Km, Vmax, or CLint) for the efflux and the metabolism regardless of whether we were using seven HFs, six DHFs, or a combination thereof. Instead, the cellular excretion of many flavonoid glucuronides appears to be controlled by the efflux transporter, and the poor affinity of glucuronide to the efflux transporter resulted in major intracellular accumulation of glucuronides to a level that is above the dosing concentration of its aglycone. Hence, the efflux transporters appear to act as the “Revolving Door” to control the cellular excretion of glucuronides. In conclusion, the determination of a flavonoid’s susceptibility to glucuronidation must be based on both its susceptibility to glucuronidation by the enzyme and resulting glucuronide’s affinity to the relevant efflux transporters, which act as the “Revolving Door(s)” to facilitate or control its removal from the cells." @default.
• W2014232034 created "2016-06-24" @default.
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• W2014232034 date "2013-04-23" @default.
• W2014232034 modified "2023-09-24" @default.
• W2014232034 title "Revolving Door Action of Breast Cancer Resistance Protein (BCRP) Facilitates or Controls the Efflux of Flavone Glucuronides from UGT1A9-Overexpressing HeLa Cells" @default.
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• W2014232034 doi "https://doi.org/10.1021/mp300562q" @default.
• W2014232034 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4030725" @default.
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