Clinical importance of the cytochromes P450

@article{Nebert2002ClinicalIO,
  title={Clinical importance of the cytochromes P450},
  author={Daniel W. Nebert and David W. Russell},
  journal={The Lancet},
  year={2002},
  volume={360},
  pages={1155-1162}
}
The human cytochrome P450 (CYP) superfamily comprises 57 genes. These genes code for enzymes that can have a role in: metabolism of drugs, foreign chemicals, arachidonic acid and eicosanoids; cholesterol metabolism and bile-acid biosynthesis; steroid synthesis and metabolism; vitamin D(3) synthesis and metabolism; retinoic acid hydroxylation; and those of still unknown function. Cytochrome P450 was once believed to be mainly a hepatic drug detoxication system, but is now understood to include a… 
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    Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology
  • 2006
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An introduction to a few of the many aspects of P450 research relating to humans is provided to introduce additional ways of thinking about metabolism and applications to topics widely taught in undergraduate courses in biochemistry are provided.
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What fraction of drug toxicity actually involves metabolism, and how species and human interindividual variations affect pharmacokinetics and toxicity are considered are considered.
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This review covers the 22 (of the total of 57) human P450s in Families 5–51 and their substrate selectivity and update and discuss important aspects of each of these 22 P 450s and questions that remain open.
Understanding the mechanism of cytochrome P450 3A4: recent advances and remaining problems.
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An overview on recent progress and remaining problems in the CYP3A4 research is provided, which shows its extreme promiscuity in substrate specificity and cooperative substrate binding often leads to undesirable drug-drug interactions and toxic side effects.
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TLDR
The mechanisms by which CYP3A4, 2B6, and 1A1 are induced involving the activation of the transcription factors pregnane X receptor, constitutive androstane receptor, and aryl hydrocarbon receptor will be discussed.
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TLDR
A two-tiered system to predict an overall inter-individual risk of tumorigenesis based on DNA variants in certain 'early defence' CYP genes, combined with polymorphisms in various downstream target genes is suggested.
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