Related Experiment Video
Updated: Aug 8, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Regulation of genes associated with drug metabolism
W H Elliott1, B K May, M J Bawden
1Adelaide University Centre for Gene Technology, Department of Biochemistry, University of Adelaide, South Australia.
Abstract:
Exposure of animals to foreign chemicals results in the induction of many enzymes. The mitochondrial enzyme 5-aminolaevulinate synthase (ALV-S) is induced to supply haem for cytochrome P-450 (P-450) enzymes, the key proteins in drug detoxification. The drugs phenobarbital and 2-allyl-2-isopropylacetamide (AIA), although structurally different, elevate levels of ALV-S and a specific class of P-450s, the phenobarbital-inducible P-450s. Synthesis of ALV-S is negatively controlled by the end-product haem and it is proposed that drugs induce P-450 apoprotein which sequesters haem. Studies at the mRNA level show that ALV-S and P-450 are drug induced in a highly tissue-specific fashion and that haem represses mRNA levels in all but erythroid tissues. In liver, drugs activate ALV-S gene transcription and haem represses, but this mechanism does not operate in erythroid cells. Studies on the drug-induction mechanism of phenobarbital-inducible P-450s in chick embryo liver show that increased mRNA levels result from P-450 gene activation together with a significant post-transcriptional mechanism.
Related Concept Videos
Regulation of Metabolism
Pharmacogenetics and Pharmacogenomics: Overview
Principles of Pharmacogenetics: Types of Genetic Variants
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Drug Metabolism: Overview
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

