NADPH--cytochrome P450 reductase (POR) (POR)

NADPH--cytochrome P450 reductase (POR) is a critical membrane-bound flavoprotein located in the endoplasmic reticulum that functions as the obligatory electron donor for all microsomal cytochrome P450 (CYP) enzymes (UniProt P16435). It plays a fundamental role in the oxidative metabolism of endogenous substrates, such as steroids, bile acids, and fatty acids, as well as the detoxification and clearance of numerous drugs and xenobiotics (NCBI Gene: 5447). POR utilizes two flavin cofactors, FAD and FMN, to shuttle electrons from NADPH to its partner enzymes. In pharmacology, POR is a key mediator of the bioreductive activation of certain anticancer prodrugs, such as tirapazamine and mitomycin C, which are converted into cytotoxic radicals in hypoxic tumor environments (Cancer Res 2009;69:7722-7728). However, this electron-transfer process can also lead to "redox cycling" of specific compounds, including the chemotherapeutic agent doxorubicin and the herbicide paraquat. This cycling generates reactive oxygen species (ROS), which can cause significant oxidative damage to cellular components and contribute to severe side effects like drug-induced cardiotoxicity (PubMed: 21939360). Genetic mutations in the POR gene are associated with cytochrome P450 reductase deficiency, a condition characterized by disordered steroidogenesis and skeletal malformations known as Antley-Bixler syndrome (PubMed: 16126718).

Other names

Cytochrome P450 reductaseCPRCYPORNADPH-dependent cytochrome P450 reductasePOR

Facilitates one-electron reduction of substrates; transfers electrons from NADPH to cytochrome P450 enzymes and other heme proteins; activates bioreductive prodrugs.