Fig. 4.

Oxidative inhibition of P450 catalytic activity. Prereduced P450 was incubated with varying concentrations of H₂O₂, or TCEP as a reduced control. Enzymes were then reconstituted and enzymatic activity assays were performed as in the experimental procedures. (A) P450 1A2 was incubated with the substrate phenacetin, and acetaminophen was monitored as the product. The reduced control enzymatic rate was 1.85 ± 0.01 min⁻¹. (B) P450 2C8 was incubated with taxol, and 6α-hydroxytaxol was monitored as the product. The reduced control enzymatic rate was calculated as 5.5 ± 0.4 min⁻¹. (C) P450 2D6 was incubated with dextromethorphan and dextrorphan was monitored as the product. The reduced control enzymatic rate was 5.6 ± 0.1 min⁻¹. (D) P450 3A4 was incubated with testosterone and 6β-hydroxytestosterone was monitored as the product. The reduced control enzymatic rate was 11.3 ± 0.3 min⁻¹. Samples were acquired in biological duplicate and presented as means ± S.D. (range).