Nicotinamide adenine dinucleotide (NAD+), the central redox coenzyme in cellular metabolism1,2functions as a hydride group acceptor, forming NADH with concomitant oxidation of metabolites derived from carbohydrates, amino acids and fats. The NAD+/NADH ratio controls the degree to which such reactions proceed in oxidative versus reductive directions. Whereas fuel oxidation reactions require NAD+as a hydride acceptor, gluconeogenesis, oxidative phosphorylation, ketogenesis, detoxification of reactive oxygen species (ROS) and lipogenesis require reduced co-factors, NADH and NADPH, as hydride donors (Fig. 1). In addition to its role as a coenzyme, NAD+ is the consumed substrate of enzymes such as poly-ADPribose polymerases (PARPs), sirtuins and cyclic ADPribose synthetases1. In redox reactions, the biosynthetic structures of NAD+, NADH, NADP+ and NADPH are preserved. In contrast, PARP3, sirtuin4and cyclic ADPribose synthetase5 activities hydrolyze the linkage between the nicotinamide (Nam) and the ADPribosyl moieties of NAD+ to signal DNA damage, alter gene expression, control post-translational modifications and regulate calcium signalling.