Enzyme Regulation

The expression and activity of enzymes associated with biotransformation are controlled by a wide range of mechanisms. The amount of the enzyme available in a cell can be regulated either at the stage of transcription or at various posttranscriptional steps. This article provides a summary of the various mechanisms identified, thus far including those affected by xenobiotic exposure, genetic polymorphisms, and epigenetic events, for the regulation of levels of biotransformation enzymes, particularly P450 enzymes. Remarkable progress has been made in our understanding of how xenobiotic compounds regulate the expression of various biotransformation enzymes, through both transcriptional and posttranscriptional mechanisms. Emphasis is placed here on the primary transcriptional regulators, including the aryl hydrocarbon receptor, the constitutive active/androstane receptor, the pregnane X receptor, the peroxisome proliferator-activated receptor α, and the nuclear factor erythroid-derived 2-related factor 2; these factors are responsible for the induction of numerous biotransformation genes, in response to exposure to xenobiotic compounds.