Nicotinamide adenine dinucleotide (phosphate)-dependent oxidoreductase (NAD(P)-oxidoreductase)

Endogenous oxidoreductase enzymes utilizing NAD/NADP as cofactors represent a vast and diverse class of proteins (EC 1) that catalyze redox reactions by transferring electrons between substrates and the nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP) coenzymes (UniProt, 2024). These enzymes are fundamental to cellular metabolism, participating in the citric acid cycle, glycolysis, fatty acid oxidation, and the pentose phosphate pathway (NCBI, 2024). In a clinical and research context, their collective activity is often used as a proxy for cellular metabolic health and viability, as seen in assays like MTT or resazurin reduction (StatPearls, 2023). While the group as a whole is not a single therapeutic target, many specific members—such as dihydrofolate reductase or HMG-CoA reductase—are critical targets for anticancer and lipid-lowering therapies (PubMed, 2023). Dysregulation of these enzymes is linked to various pathologies, including cancer, where metabolic reprogramming (the Warburg effect) alters redox balance to support rapid proliferation (Nature Reviews Cancer, 2022). Furthermore, these enzymes play a crucial role in the detoxification of reactive oxygen species and the maintenance of the cellular antioxidant defense system (Journal of Biological Chemistry, 2021). Drugs targeting this class typically act as competitive inhibitors of either the substrate binding site or the cofactor binding pocket (Pharmacological Reviews, 2020). Because of their central role in energy production, targeting these enzymes requires high specificity to avoid systemic metabolic toxicity (Trends in Pharmacological Sciences, 2022).

Other names

NAD/NADP-dependent dehydrogenasesNicotinamide adenine dinucleotide-linked oxidoreductasesPyridine nucleotide-dependent oxidoreductasesNAD(P)H-dependent reductases

Catalysis of electron or hydride transfer between a substrate and the nicotinamide ring of NAD+/NADH or NADP+/NADPH cofactors to facilitate metabolic transformations.