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• W2076638657 startingPage "432" @default.
• W2076638657 abstract "Recently, we reported that several endogenous steroids affect CYP3A4-mediated drug metabolism, using human adult liver microsomes as an enzyme source. Especially, carbamazepine (CBZ) 10,11-epoxidation is activated by androstenedione (AND). In the present studies, we investigated the effects of endogenous steroids on the activity of CBZ 10,11-epoxidation by expressed CYP3A4 and CYP3A7. When expressed CYP3A4 was used as an enzyme source, the addition of AND to the reaction mixture also caused a drastic increase in the activity of CBZ 10,11-epoxidase, and resulted in a change in the kinetics from sigmoid to Michaelis-Menten type. On the other hand, expressed CYP3A7-mediated CBZ 10,11-epoxidation was activated by sulfate conjugate steroids, such as pregnenolone 3-sulfate, 17α-hydroxypregnenolone 3-sulfate, and dehydroepiandrosterone 3-sulfate (DHEA-S), whereas the unconjugated form corresponding to these three steroids did not activate the reaction. Especially, DHEA-S was found to be a potent activator of CBZ 10,11-epoxidation by expressed CYP3A7. The kinetic character of CBZ 10,11-epoxidation by CYP3A7 is Michaelis-Menten type regardless of the presence of DHEA-S. The presence of DHEA-S caused a decrease in<i>K</i>_m and increase in<i>V</i>_max for CYP3A7-mediated CBZ 10,11-epoxidation, whereas DHEA-S 16α-hydroxylation was not affected by the coexistence of CBZ. In conclusion, CYP3A4 and CYP3A7-mediated CBZ 10,11-epoxidations are activated by different types of endogenous steroids. This is the first report regarding CYP3A7 cooperativity." @default.
• W2076638657 created "2016-06-24" @default.
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• W2076638657 date "2003-04-01" @default.
• W2076638657 modified "2023-10-16" @default.
• W2076638657 title "CYP3A4 and CYP3A7-Mediated Carbamazepine 10,11-Epoxidation Are Activated by Differential Endogenous Steroids" @default.
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• W2076638657 doi "https://doi.org/10.1124/dmd.31.4.432" @default.
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