BMAL1-mediated transcriptional regulation of CYP3A13 drives circadian rhythms in intestinal first-pass metabolism

CYP3A13 expression is significantly higher during the night compared to the day.

• The CYP3A family is primarily expressed in the jejunum, with CYP3A13 being the most prevalent isoform.
• CYP3A13 exhibits a robust circadian rhythm in expression and metabolic activity.
• The circadian clock gene Bmal1 is associated with the regulation of CYP3A13 expression and function.
• Bmal1 directly activates CYP3A13 by binding to an E-box element, as shown through luciferase reporter assays and chromatin immunoprecipitation (ChIP).
• The findings suggest that circadian rhythms may influence the metabolism of orally administered drugs like verapamil.

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