Nicotinamide adenine dinucleotide-binding metabolic enzymes (NAD+-binding enzymes)

Nicotinamide adenine dinucleotide (NAD+)-binding metabolic enzymes are a broad class of proteins that utilize NAD+ as a critical cofactor or substrate to regulate cellular metabolism and signaling. This group includes oxidoreductases, such as dehydrogenases involved in glycolysis and the citric acid cycle, which use the NAD+/NADH redox couple to facilitate electron transfer (Canto et al., 2015, Cell Metabolism). Additionally, it encompasses NAD+-consuming enzymes like sirtuins (SIRTs), poly(ADP-ribose) polymerases (PARPs), and CD38, which utilize NAD+ to mediate protein deacetylation, DNA repair, and calcium signaling, respectively (Houtkooper et al., 2010, Endocrine Reviews). Because NAD+ levels decline with age and are altered in various diseases, these enzymes are major therapeutic targets. For example, PARP inhibitors are clinically approved for treating BRCA-mutated cancers by inducing synthetic lethality, while sirtuin activators and CD38 inhibitors are being explored for their potential to treat metabolic and age-related disorders (Navas & Carnero, 2021, Archives of Toxicology). The ubiquity of NAD+ in cellular processes makes these enzymes central to health, but also presents challenges in achieving tissue-specific therapeutic effects without systemic toxicity (Chini et al., 2018, Trends in Pharmacological Sciences).

Other names

NAD-dependent enzymesNAD+-consuming enzymesNAD-binding proteinsOxidoreductases (NAD-dependent)

Inhibition of NAD+ binding or consumption; modulation of redox-dependent enzymatic activity; activation of sirtuin-mediated deacetylation; inhibition of poly(ADP-ribose) polymerase activity.