Por

Por Full Name

P450 (cytochrome) oxidoreductase

Por Introduction

POR, or P450 oxidoreductase, is a flavoprotein involved in the transfer of electrons to microsomal cytochrome P450 enzymes. Its membrane bound to endoplasmic reticulum and contains the two cofactors FAD and FMN. As a result of these traits, the protein can shuttle electrons from NADPH to a wide range of P450 isoforms. As the overwhelming majority of microsomal P450 enzymes require POR for catalytic activity, the protein has a functional relationship with a first level of xenobiotic metabolism, steroidogenesis and many oxidative biochemical pathways. As such, POR's broad substrate involvement makes it a master regulator of metabolic homeostasis.

Figure 1. Genome-wide CRISPR screens identify POR as a mediator of ferroptosis.(Source: Zou Y, et al.; 2020)

Functionally, POR has a broad range of activities. The main function of POR is to enable P450s to catalyze the hydroxylation, demethylation and epoxidation steps in drug metabolism, and the biosynthesis of cholesterol, steroid hormones, retinoic acid metabolism, and lipid homeostasis. POR also couples to a number of other redox partners, including heme oxygenase and cytochrome b5. Alterations in POR can lead to changes in pharmacokinetics, which can result in altered drug responses and clearance of other relevant clinical compounds. POR is also crucial to steroid biosynthesis during development where the regulated activity of the enzymes controls levels of sex steroids and glucocorticoids.

Clinically, mutations in POR lead to a collection of syndromes called P450 oxidoreductase deficiency (PORD). The most clinically significant findings are a partial defect of steroidogenesis that can cause ambiguous genitalia, adrenal insufficiency and skeletal malformations that resemble Antley–Bixler syndrome. Some POR polymorphisms can alter drug metabolism and may account for some of the variability in drug therapy responses among individuals. They act by altering the activity of CYP3A4, CYP2C9 and possibly other major drug metabolizing enzymes, and therefore alter the efficacy and toxicity of drugs. Altered POR function has also recently been implicated in the etiology of metabolic disease, endocrine disorders, and cholesterol homeostasis.

Alternate Names for Por

POR; P450 (cytochrome) oxidoreductase; CPR; CYPOR; P450R; NADPH--cytochrome P450 reductase; NADPH-dependent cytochrome P450 reductase;

• 1.Zou Y, et al.; Cytochrome P450 oxidoreductase contributes to phospholipid peroxidation in ferroptosis. Nat Chem Biol. 2020, 16(3):302-309.