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, 2B6, 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.
Tompkins
Leslie M
LM
Department of Environmental & Molecular Toxicology, Campus Box 7633, North Carolina State University, Raleigh, NC 27695-7633, USA
Wallace
Andrew D
AD
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D000090702:Constitutive Androstane Receptor; D019363:Cytochrome P-450 CYP1A1; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008954:Models, Biological; D010089:Oxidoreductases, N-Demethylating; D000077297:Pregnane X Receptor; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D011987:Receptors, Steroid / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D015262:Xenobiotics / Q000737:chemistry / Q000494:pharmacology
D000090702:Constitutive Androstane Receptor; D007527:Isoenzymes; D000077297:Pregnane X Receptor; D018336:Receptors, Aryl Hydrocarbon; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D019363:Cytochrome P-450 CYP1A1; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D010089:Oxidoreductases, N-Demethylating