Molecular modeling of cytochrome P450 and drug metabolism

Curr Drug Metab. 2010 May;11(4):342-6. doi: 10.2174/138920010791514180.

Abstract

The cytochrome P450 family is a large and diverse group of hemoproteins that are located in virtually all types of organism, such as bacteria, eukaryotes and even Archaea. These proteins are found throughout the body, however the highest concentrations are associated with liver. As the Human Genome Project completed, there are 57 genes and more than 59 pseudogenes divided among 18 families of CYP genes and 43 subfamilies have been detected. In humans, CYPs are the major enzymes involved in drug metabolism and bioactivation, accounting for almost 75% of the total drug metabolism. The variability in drug metabolisms that are mainly induced by the CYP polymorphisms is reflected on the differences of the maximal plasma concentrations, half lives of some drugs and their clearance. Besides, it can also lead to adverse drug reactions that are considered as a major factor in drug toxicity. So, the genotype-activity relationships of the CYP proteins have become a hot topic in recent years. It is important to further understand why a certain genotype influences enzyme activity and how to predict more structure-activity relationships.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • Drug-Related Side Effects and Adverse Reactions
  • Genotype
  • Half-Life
  • Humans
  • Liver / enzymology
  • Models, Molecular*
  • Pharmaceutical Preparations / metabolism*
  • Polymorphism, Genetic
  • Structure-Activity Relationship

Substances

  • Pharmaceutical Preparations
  • Cytochrome P-450 Enzyme System