کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9037466 | 1133435 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of human cytochrome P450 3A4 activity by zinc(II) ion
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
Effects of Zn2+ on the activity and conformation of cytochorome P450 3A4 (CYP3A4) were investigated. Zn2+ specifically inhibited the testosterone 6β-hydroxylation activity of CYP3A4 with an IC50 value of 27 μM. 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 156, Issue 3, 28 April 2005, Pages 341-350
Journal: Toxicology Letters - Volume 156, Issue 3, 28 April 2005, Pages 341-350
نویسندگان
Joon-Sik Kim, Chul-Ho Yun,