NADH-cytochrome b5 reductase 1 (CYB5R1)

NADH-cytochrome b5 reductase 1 (CYB5R1) is a flavin-containing oxidoreductase enzyme that catalyzes electron transfer from NADH to cytochrome b5, supporting critical metabolic processes including fatty acid desaturation, cholesterol biosynthesis, drug metabolism, and methemoglobin reduction in erythrocytes[1][3][4]. The enzyme exists in both membrane-bound (microsomal) and soluble forms, with the membrane-bound isoform localized to the endoplasmic reticulum and outer mitochondrial membrane, where it interacts with cytochrome b5 and participates in detoxification pathways[4][7]. Structurally, CYB5R1 is a 305-amino acid protein (~34.1 kDa) with distinct FAD and NADH-binding domains, and it is encoded by the CYB5R1 gene located at 1q32.1[2][3]. In cancer biology, CYB5R1 is implicated in epithelial-mesenchymal transition, tumor cell migration, and invasion in colorectal cancer, correlating with poor prognosis[5]. The enzyme’s role in electron transfer and redox homeostasis also links it to oxidative stress protection and apoptosis prevention[5]. Despite its biological importance, CYB5R1 is not currently a direct target of any approved drugs, although its activity may influence the metabolism of certain xenobiotics[5][6].

Other names

NQO3A2UNQ3049/PRO9865b5R.1humb5R2Humb5R2NAD(P)H:quinone oxidoreductase type 3 polypeptide A2B5R.1B5R1B5R2NAD(P)H:quinone oxidoreductase type 3, polypeptide A2NADH-cytochrome b5 reductase 1

No drugs with a direct, clinically validated mechanism of action on CYB5R1 are known. Research indicates potential for small molecule modulation, but no FDA-approved agents target this enzyme directly. Indirectly, drugs metabolized by cytochrome P450 or dependent on fatty acid/cholesterol pathways might be affected by CYB5R1 activity, but this is not a direct mechanism.