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 language | English (US) |
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Pages (from-to) | 439-452 |
Number of pages | 14 |
Journal | Expert Opinion on Drug Metabolism and Toxicology |
Volume | 4 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2008 |
Keywords
- Cytochrome P450 oxidoreductase
- Drug metabolism
- Genetic polymorphism
- POR
- Pharmacogenetics
- Toxicity
ASJC Scopus subject areas
- Toxicology
- Pharmacology