Nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+) dependent enzyme systems (NAD/NADP pathways)

Nicotinamide adenine dinucleotide (NAD+) and its phosphate derivative (NADP+) are essential cofactors that facilitate hundreds of redox reactions and serve as critical substrates for signaling enzymes (Canto et al., 2015, Cell Metabolism). NAD+ is central to catabolic energy production in the mitochondria and cytoplasm, while also acting as a necessary substrate for PARPs, sirtuins, and CD38, which govern DNA repair, epigenetic regulation, and calcium signaling (Verdin, 2015, Science). NADP+ and its reduced form NADPH are vital for anabolic processes like lipid biosynthesis and the maintenance of cellular antioxidant defenses through the glutathione system (Covarrubias et al., 2021, Nature Reviews Molecular Cell Biology). Dysregulation of these pathways is a hallmark of aging and contributes to the pathogenesis of cancer, neurodegenerative diseases, and metabolic disorders (Navas & Carnero, 2021, Signal Transduction and Targeted Therapy). Therapeutic strategies targeting these systems include the use of NAD+ precursors to counteract age-related decline and the development of inhibitors for NAD+-consuming enzymes to treat specific malignancies and inflammatory conditions.

Other names

NAD metabolismPyridine nucleotide-dependent enzymesRedox cofactor pathwaysNAD+ biosynthesis and consumption pathwaysNAD+ / NADP+ dependent enzyme systems – general metabolic cofactor pathways

Modulation of NAD+ biosynthesis (e.g., NAMPT inhibition), activation of NAD+-dependent signaling (e.g., Sirtuin activation), or inhibition of NAD+-consuming enzymes (e.g., PARP or CD38 inhibition).