NMNAT1 Human

Nicotinamide Nucleotide Adenylyltransferase 1 (NMNAT1) is an enzyme that plays a crucial role in the biosynthesis of nicotinamide adenine dinucleotide (NAD), a coenzyme involved in numerous metabolic processes. NMNAT1 is one of three isoforms of nicotinamide nucleotide adenylyltransferases found in humans, the other two being NMNAT2 and NMNAT3 .

NMNAT1 is encoded by the NMNAT1 gene located on chromosome 1 in humans . The enzyme catalyzes the condensation of nicotinamide mononucleotide (NMN) or nicotinic acid mononucleotide (NaMN) with the AMP moiety of ATP to form NAD or NaAD . This reaction is essential for the maintenance of cellular NAD levels, which are critical for various metabolic redox reactions, protein ADP-ribosylation, histone deacetylation, and some calcium signaling pathways .

Humans have three NMNAT isoforms:

• NMNAT1: Predominantly localized in the nucleus .
• NMNAT2: Found mainly in the cytoplasm and is critical for neuronal health .
• NMNAT3: Present in the mitochondria or cytoplasm, with the highest expression in the liver, heart, skeletal muscle, and erythrocytes .

Mutations in the NMNAT1 gene are associated with Leber congenital amaurosis 9 (LCA9), a severe retinal dystrophy that leads to early-onset blindness . NMNAT1 is also involved in the protection of damaged neurons through the activation of a nuclear deacetylase . Chronic inflammation due to obesity and other causes can reduce NMNAT and NAD levels in many tissues, highlighting the enzyme’s importance in maintaining cellular health .

Research on NMNAT1 has shown its potential as a neuroprotective agent. The enzyme’s ability to maintain NAD levels and protect neurons makes it a promising target for therapeutic interventions in neurodegenerative diseases . Additionally, NMNAT1’s role in NAD biosynthesis has led to interest in NAD-boosting molecules as potential treatments for age-related decline and metabolic disorders .