Glutamine-dependent NAD(+) synthetase (NADSYN1)

Glutamine-dependent NAD(+) synthetase (NADSYN1) is a key enzyme that catalyzes the final, ATP-dependent amidation step in the biosynthesis of nicotinamide adenine dinucleotide (NAD^+), converting deamido-NAD^+ to NAD^+ using L-glutamine (or ammonia in some isoforms) as the amide donor[2][4][6]. This enzyme is essential for both de novo and salvage NAD^+ biosynthetic pathways and is found in all domains of life, including humans, where two isoforms exist with differential tissue distribution and amide-donor specificity: NADSYN1 (glutamine-dependent) and NADSYN2 (ammonia-dependent)[2][6]. As the last step in NAD^+ synthesis, it is crucial for energy metabolism, redox balance, DNA repair, chromatin remodeling, transcriptional regulation, and cell viability[3][5][7]. Dysregulation is implicated in diseases involving cell proliferation, neurodegeneration, or chronic inflammation. NAD synthetase is a potential target for novel therapeutics, particularly in oncology and infectious disease, but broad inhibition may cause systemic toxicity due to NAD^+ depletion in normal tissues[5][7][8].

Other names

NAD synthetaseNAD^+ synthetaseNicotinamide adenine dinucleotide synthetaseDeamido-NAD^+ aminaseNADSYNDeamido-NAD^+ synthase

Inhibitors would block the final step of NAD biosynthesis, reducing cellular NAD^+ levels and affecting energy metabolism and survival, especially in cancer cells that rely on salvage or de novo NAD^+ synthesis[5][8]