Nicotinamide mononucleotide adenylyltransferase (NMNAT) (NMNAT)

Nicotinamide mononucleotide adenylyltransferase (NMNAT) is a vital enzyme responsible for the final step of nicotinamide adenine dinucleotide (NAD+) biosynthesis in both the de novo and salvage pathways. In humans, three distinct isoforms (NMNAT1, NMNAT2, and NMNAT3) are localized to the nucleus, cytosol/Golgi, and mitochondria, respectively, ensuring NAD+ availability across different cellular compartments (UniProt). NMNAT catalyzes the transfer of an adenylyl group from ATP to nicotinamide mononucleotide (NMN) or nicotinic acid mononucleotide (NaMN). Beyond its metabolic function, NMNAT2 is a critical neuroprotective factor; its presence is essential for axonal survival, and its degradation is a hallmark of Wallerian degeneration (PubMed: 22445511). Mutations in NMNAT1 are linked to Leber congenital amaurosis type 9, a severe form of childhood blindness (PubMed: 23022100). As a therapeutic target, NMNAT is being explored for neurodegenerative diseases like Alzheimer's and glaucoma, where enhancing its activity may prevent neuronal loss (PubMed: 30612034). Additionally, because NMNAT can process certain xenobiotics, it can inadvertently convert pro-toxins like the rodenticide Vacor into toxic NAD+ analogs, leading to rapid neurodegeneration (PubMed: 33301215).

Other names

NMN adenylyltransferaseNicotinate-nucleotide adenylyltransferaseNaMN adenylyltransferasePNATPyridine nucleotide adenylyltransferase

Catalyzes the reversible transfer of the adenylyl group from ATP to nicotinamide mononucleotide (NMN) or nicotinic acid mononucleotide (NaMN) to form NAD+ or NaAD, respectively.