Scheme 3.

Model of Heterotropic and Homotropic Cooperativity of MDZ Metabolism by CYP3A4.

A) CYP3A4 without ligands. B) CYP3A4 with a single molecule of MDZ oriented with the 1′-CH3 close to the heme. C) Competitive inhibition of MDZ formation by CBZ at low [MDZ] D) CYP3A4 with an effector molecule of MDZ or CBZ that forces the 4-position of the MDZ closer to the heme. The double arrows reflect the equilibrium between the various states. The solid and the dashed arrows reflect increasing and decreasing rates of product formation, respectively.