Mechanisms of cytochrome P450 induction

Cytochrome P450s (CYPs) are important heme-containing proteins that play important roles in the metabolism of xenobiotics and endogenous compounds. The oxidative metabolisms of drugs, environmental chemicals, hormones, and fatty acids by CYP enzymes are critical pathways aiding in their excretion from the body, but in some cases metabolism may lead to bioactivation and enhanced toxicity. The expression and activity levels of CYPs can be elevated by a process of induction involving the activation of key transcription factors. The mechanisms by which CYP3A4, 2136, and 1A1 are induced involving the activation of the transcription factors pregnane X receptor (PXR), constitutive androstane receptor (CAR), and aryl hydrocarbon receptor (AhR) will be discussed. (c) 2007 Wiley Periodicals,Inc.