Mechanism-based inactivation effects of TAA in P450s in vitro
TAA (0, 5, 50, 200, and 400 μM) was incubated with normal rat liver microsomes containing a NADPH regenerating system; the remaining enzyme activity was then determined by a typical dilution method. KI and kinact values were calculated from the Kitz-Wilson plot; kinact/KI values were calculated to indicate the inactivation rate.
| P450 Isozymes | KI | kinact | kinact/KI |
|---|---|---|---|
| μM | min−1 | min−1/μM−1 | |
| CYP1A2 | 10.558 | 0.018 | 0.0017 |
| CYP2C6 | 22.812 | 0.074 | 0.0033 |
| CYP3A2 | 58.914 | 0.056 | 0.0010 |
| CYP2E1 | 6.700 | 0.026 | 0.0039 |