Implications of the allosteric kinetics of cytochrome P450s

Drug metabolites can uniquely contribute to therapeutic efficacy, toxicity and drug-drug interactions. Therefore, the rates of formation and clearance of each metabolite are crucially important parameters in the net therapeutic profile of new drugs. However, the recent appreciation for the importance of drug metabolism has made it apparent that the understanding of the fundamental kinetic and biophysical properties of the enzymes that are responsible for catalyzing these reactions, the cytochrome P450s, is incomplete. The need to fully comprehend the complex allosteric behavior of these enzymes has fostered increased scrutiny of cytochrome P450s, which has subsequently resulted in major changes in the way that these enzymes are perceived at the molecular level.