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Updated: Aug 19, 2026

Characterizing Mammalian Zinc Transporters Using an In Vitro Zinc Transport Assay
Published on: June 2, 2023
Inhibition of human cytochrome P450 3A4 activity by zinc(II) ion
1AngioLab, Paichai University, Taejon 302-735, Republic of Korea.
Abstract:
Effects of Zn2+ on the activity and conformation of cytochorome P450 3A4 (CYP3A4) were investigated. Zn2+ specifically inhibited the testosterone 6beta-hydroxylation activity of CYP3A4 with an IC50 value of 27 microM. Zn2+ inhibited the CO-binding spectra of CYP3A4 reduced by NADPH-cytochrome P450 reductase (CPR) and NADPH only in the presence of b5. Zn2+-induced conformational changes of CYP3A4 were monitored by CD and intrinsic fluorescence. Zn2+ showed no significant effects on the activity of CYP3A4 supported by tert-butyl hydroperoxide, an oxygen surrogate, and on the reduction of b5 by CPR and NADPH. These results suggest that the inhibitory effects of Zn2+ come from preventing the stimulation of b5 on CYP3A4 activity.
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