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TCDD (2, 3, 7, 8-tetrachlorodibenzo-p-dioxin) is a tight binding inhibitor of cytochromep-450D

✍ Scribed by Voorman, Richard ;Aust, Steven D.

Publisher
John Wiley and Sons
Year
1989
Tongue
English
Weight
487 KB
Volume
4
Category
Article
ISSN
0887-2082

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✦ Synopsis

Based on data indicating that compounds which induce cytochrome P-450d also bind to the enzyme [R. Voorman and S. D. Aust (1987). Toxicol. Appl. Pharmacol. 90, 69-781, we investigated the inhibition of cytochrome P-45Od-dependent estradiol 2-hydroxylase by (2,3,7,8-tetrachlorodibenzo-pdioxin TCDD), using ligand-free cytochrome P-450d from isosafrole-treated rats. Since maximum inhibition of estradiol 2-hydroxylase occurred at TCDD concentrations comparable to the concentration of enzyme (50 nM), a modified form of steady-state kinetic analysis was used. Using Is0 = Etiz + Ki where Et = total enzyme concentration), we showed that TCDD inhibited cytochrome P-450d-dependent estradiol 2-hydroxylase activity with Ki equal to 8 nM. Association of TCDD with P-450d occurred within 2 min of inhibitor addition. Therefore, TCDD can be considered a tight binding inhibitor of cytochrome P- 450d.

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