NADPH--cytochrome P450 reductase (POR)

NADPH--cytochrome P450 reductase (POR) is a vital membrane-bound flavoprotein located in the endoplasmic reticulum that serves as the obligatory electron donor for all microsomal cytochrome P450 (CYP) enzymes (UniProt: P16435). It facilitates the transfer of electrons from NADPH through its FAD and FMN moieties to the heme center of CYPs, enabling the oxidative metabolism of a vast range of substrates, including steroids, fatty acids, and xenobiotics (PubMed: 22461012). Beyond its role in endogenous metabolism, POR is critical for the bioactivation of bioreductive anticancer prodrugs like Mitomycin C and Tirapazamine, particularly in hypoxic tumor environments (PubMed: 15632148). Genetic mutations in the POR gene lead to Cytochrome P450 Reductase Deficiency, which manifests as skeletal abnormalities, disordered steroidogenesis, and impaired drug metabolism (NCBI Gene: 5447). Understanding POR activity is essential for predicting individual drug response and toxicity profiles, as it directly governs the catalytic efficiency of the entire microsomal P450 system.

Other names

Cytochrome P450 reductaseCPRP450RNADPH-dependent cytochrome P450 reductaseFLJ26468

POR functions as the essential electron donor for microsomal cytochrome P450 enzymes and also acts as a bioreductive activator for certain anticancer prodrugs by transferring electrons to them under hypoxic conditions.