Clinical importance of the cytochromes P450

  title={Clinical importance of the cytochromes P450},
  author={Daniel W. Nebert and David W. Russell},
  journal={The Lancet},

Proteomic analysis of cytochromes P450: a mass spectrometry approach.

MS provides a convenient method for the identification and quantification of CYP enzymes, and in the present paper the current state of the technology for such an analysis is reviewed.

Cytochromes P450 and drug discovery.

Human cytochrome P450 enzymes 5–51 as targets of drugs and natural and environmental compounds: mechanisms, induction, and inhibition – toxic effects and benefits

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.

Cytochrome P450 Polymorphisms

This chapter summarizes the functional, clinical, and toxicological relevance of human P450 genetic polymorphism, which affects all drug-metabolizing CYPs, but to a very different extent.

Cytochrome P450 enzymes in drug metabolism and chemical toxicology: An introduction

  • L. FurgeF. Guengerich
  • Biology
    Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology
  • 2006
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.

Cytochrome P450s and other enzymes in drug metabolism and toxicity

What fraction of drug toxicity actually involves metabolism, and how species and human interindividual variations affect pharmacokinetics and toxicity are considered are considered.

Understanding the mechanism of cytochrome P450 3A4: recent advances and remaining problems.

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.

Mechanisms of cytochrome P450 induction

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.

The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis

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.



Twenty years of biochemistry of human P450s: purification, expression, mechanism, and relevance to drugs.

Some recently developed bacterial systems that can be used for the production of metabolites, genotoxicity testing, and screening in random mutagenesis work are described.

The cytochrome P450 4 (CYP4) family.

  • A. Simpson
  • Biology, Chemistry
    General pharmacology
  • 1997

Regulation of cyp3a gene transcription by the pregnane x receptor.

The pregnane X receptor (PXR) is a promiscuous nuclear receptor that has evolved to protect the body from toxic chemicals and may prove useful in the treatment of diseases in which toxic metabolites accumulate, such as cholestatic liver disease.

Induction of cytochromes P450.

M mammals have evolved mechanisms to induce proteins involved in xenobiotic detoxification, andabolism by Phase I enzymes, particularly the heme containing monooxygenases cytochromes P450 is frequently the first line of defense against such xenobiotics.

Cytochrome P450 enzymes in the bioactivation of vitamin D to its hormonal form (review).

  • K. Wikvall
  • Biology, Chemistry
    International journal of molecular medicine
  • 2001
The results suggest a role for CYP27A as a renal mitochondrial 1alpha-hydroxylase in the bioactivation of vitamin D3 under normal and pathological conditions and to discuss the results in relation to other published literature on these enzymes.

Xenobiotic-metabolizing Cytochromes P450 Convert Prostaglandin Endoperoxide to Hydroxyheptadecatrienoic Acid and the Mutagen, Malondialdehyde*

The results suggest that co-expression of cyclooxygenase-2 and P450s in developing cancers may contribute to genomic instability due to production of the endogenous mutagen, MDA.