P450 oxidoreductase: Genetic polymorphisms and implications for drug metabolism and toxicity

Steven N. Hart, Xiao Bo Zhong

Research output: Contribution to journalReview article

42 Scopus citations

Abstract

Background: Cytochrome P450 oxidoreductase (POR) is the only electron donor for all microsomal cytochrome P450 monooxygenases (CYP), some of which are phase I drug-metabolizing enzymes, responsible for oxidation of more than 80% of drugs. Objectives: To provide a more thorough understanding of the genetic factors influencing drug metabolism, we address the role of genetic polymorphisms in the POR gene, and their implications for drug metabolism and cytotoxicity. Methods: The scope of this review is intended to cover polymorphisms currently identified in the POR gene, assess their functional significance on POR activity, and address their impact on CYP-mediated drug metabolism. POR is also responsible for directly metabolizing several anticancer prodrugs via a 1-electron reduction reaction, so the effect of POR polymorphisms on the direct bioactivation of drugs is also considered. Results/conclusion: POR is a polymorphic enzyme that can affect CYP-mediated drug metabolism as well as direct bioactivation of prodrugs. Genetic polymorphisms in the POR gene may help to explain altered drug-metabolizing phenotypes.

Original languageEnglish (US)
Pages (from-to)439-452
Number of pages14
JournalExpert Opinion on Drug Metabolism and Toxicology
Volume4
Issue number4
DOIs
StatePublished - Apr 1 2008

Keywords

  • Cytochrome P450 oxidoreductase
  • Drug metabolism
  • Genetic polymorphism
  • POR
  • Pharmacogenetics
  • Toxicity

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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