Glutamine-dependent NAD+ synthetase (NADSYN1) (NADSYN1)

Glutamine-dependent NAD+ synthetase (NADSYN1) is an essential enzyme that catalyzes the final step in the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a vital coenzyme for cellular energy metabolism and a key substrate for enzymes involved in DNA repair and calcium signaling (UniProt: Q6IA69). The enzyme facilitates the ATP-dependent amidation of deamido-NAD+ (NaAD) to form NAD+, utilizing either glutamine or ammonia as the nitrogen donor (PubMed: 15358770). In humans, NADSYN1 is a key component of the Preiss-Handler and de novo synthesis pathways, and its deficiency is linked to severe congenital malformations known as VCRL syndrome (PubMed: 28708992). Because NAD+ is indispensable for bacterial survival and the bacterial enzyme structure differs significantly from the human counterpart, NAD+ synthase is a high-priority target for developing broad-spectrum antibacterial agents (PubMed: 12459127). Research into NAD+ synthase inhibitors also extends to oncology, as cancer cells often exhibit an increased demand for NAD+ to support rapid proliferation and DNA maintenance (PubMed: 30244144). Current drug discovery efforts focus on identifying small molecules that can selectively inhibit the bacterial enzyme or modulate human NAD+ levels to treat metabolic and age-related diseases.

Other names

NAD+ synthaseNAD+ synthetaseGlutamine-hydrolyzing NAD+ synthetaseDeamido-NAD+ amidotransferaseNicotinamide adenine dinucleotide synthetaseNadE

Inhibition of the ATP-dependent amidation of deamido-NAD+ to NAD+