Nicotinamide-nucleotide adenylyltransferase
Template:Infobox enzyme In enzymology, nicotinamide-nucleotide adenylyltransferase (NMNAT) (Template:EC number) are enzymes that catalyzes the chemical reaction
- ATP + nicotinamide mononucleotide diphosphate + NAD+
Thus, the two substrates of this enzyme are ATP and nicotinamide mononucleotide (NMN), whereas its two products are diphosphate and NAD+.
This enzyme participates in nicotinate and nicotinamide metabolism.
Humans have three protein isoforms: NMNAT1 (widespread), NMNAT2 (predominantly in brain), and NMNAT3 (highest in liver, heart, skeletal muscle, and erythrocytes).[1] Mutations in the NMNAT1 gene lead to the LCA9 form of Leber congenital amaurosis.[1] Mutations in NMNAT2 or NMNAT3 genes are not known to cause any human disease.[1] NMNAT2 is critical for neurons: loss of NMNAT2 is associated with neurodegeneration.[1] All NMNAT isoforms reportedly decline with age.[2]
Belongs to
This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing nucleotide groups (nucleotidyltransferases). The systematic name of this enzyme class is ATP:nicotinamide-nucleotide adenylyltransferase. Other names in common use include NAD+ pyrophosphorylase, adenosine triphosphate-nicotinamide mononucleotide transadenylase, ATP:NMN adenylyltransferase, diphosphopyridine nucleotide pyrophosphorylase, nicotinamide adenine dinucleotide pyrophosphorylase, nicotinamide mononucleotide adenylyltransferase, and NMN adenylyltransferase.Template:Cn
Structural studies
As of late 2007, 11 structures have been solved for this class of enzymes, with PDB accession codes Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, and Template:PDB link.
Isoform cellular localization
The three protein isoforms have the following cellular localizations[3]
- NMNAT1 : Nucleus
- NMNAT2 : Cytoplasm
- NMNAT3 : Mitochondrion or cytoplasm
All three NMNATs compete for the NMN produced by NAMPT.[4]
Clinical significance
Chronic inflammation due to obesity and other causes reduced NMNAT and NAD+ levels in many tissues.[5]