Cytochromes P450: Xenobiotic metabolism, regulation and clinical importance
Les cytochromes P450: Métabolisme des xénobiotiques, régulation et rôle en clinique
Résumé
Cytochromes P450 (CYPs) are a superfamily of 57 genes coding for drug metabolizing enzymes and endobiotic metabolizing enzymes (steroids, eicosanoids, vitamins...). This is the main metabolizing enzyme system for foreign compounds, including drugs, which has a primary role in organism protection against potential harmful insults from the environment (pollutants, pesticides...). The CYPs regulation is essentially transcriptional: nuclear receptors are recognized as key mediators for the control of drug metabolizing enzymes. Their ligands are exogenous and also endogenous molecules that can up-regulate or down-regulate these transcription factors. Treatment with drugs or xenobiotics, which are nuclear receptor agonists or antagonists, can lead to severe toxicities, loss of therapeutic effect or endobiotic metabolism disorders. Genetic polymorphisms of these enzymes have an important role in their activity and must be taken into account during drug administration. Then, CYP activity depends on genotype and environment; this is recently used as biomarker to determine human exposure to environmental molecules or to predict the susceptibility to certain pathologies.
Mots clés
cytochrome P450
xenobiotic agent
biological model
chemical structure
chemistry
gene expression regulation
genetic polymorphism
genetic transcription
genetics
homeostasis
human
kinetics
metabolism
review
Cytochrome P-450 Enzyme System
Gene Expression Regulation
Enzymologic
Homeostasis
Humans
Kinetics
Models
Biological
Molecular
Polymorphism
Genetic
Transcription
Xenobiotics