Mechanistic analysis of the inactivation of cytochrome P450 2B6 by phencyclidine: effects on substrate binding, electron transfer, and uncoupling.

@article{Shebley2009MechanisticAO,
  title={Mechanistic analysis of the inactivation of cytochrome P450 2B6 by phencyclidine: effects on substrate binding, electron transfer, and uncoupling.},
  author={Mohamad Shebley and Ute M. Kent and David P. Ballou and Paul F. Hollenberg},
  journal={Drug metabolism and disposition: the biological fate of chemicals},
  year={2009},
  volume={37 4},
  pages={745-52}
}
Phencyclidine (PCP) is a mechanism-based inactivator of cytochrome P450 (P450) 2B6. We have analyzed several steps in the P450 catalytic cycle to determine the mechanism of inactivation of P450 2B6 by PCP. Spectral binding studies show that binding of benzphetamine, a type I ligand, to P450 2B6 was significantly affected as a result of the inactivation, whereas binding of the inhibitor n-octylamine, a type II ligand, was not compromised. Binding of these ligands to P450 2B6 occurs in two phases… CONTINUE READING