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Enzyme Regulation *

Authors
  • Ding, X.
  • Zhang, Q.-Y.
Type
Book
Journal
Comprehensive Toxicology
Publication Date
Jan 01, 2010
Pages
9–29
Identifiers
DOI: 10.1016/B978-0-08-046884-6.00402-4
ISBN: 978-0-08-046884-6
Source
Elsevier
Keywords
License
Unknown

Abstract

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 post-transcriptional steps. This chapter provides a summary of 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 transcription of various biotransformation enzymes, but much less has been learned as to how xenobiotic compounds regulate post-transcriptional events. Thus, emphasis is placed here on the primary transcriptional regulators, including the aryl hydrocarbon receptor (AhR), the constitutive active/androstane receptor (CAR), the pregnane X receptor (PXR), the peroxisome proliferator-activated receptor α (PPARα), and the nuclear factor erythroid-derived 2-related factor 2 (Nrf2); these factors are responsible for the induction of numerous biotransformation genes, in response to exposure to xenobiotic compounds.

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