Nicotinamide-nucleotide adenylyltransferase
From Wikipedia the free encyclopedia
| nicotinamide-nucleotide adenylyltransferase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Nicotinamide-nucleotide adenylyltransferase (nuclear) hexamer, Human | |||||||||
| Identifiers | |||||||||
| EC no. | 2.7.7.1 | ||||||||
| CAS no. | 9032-70-6 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
In enzymology, nicotinamide-nucleotide adenylyltransferase (NMNAT) (EC 2.7.7.1) 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[edit]
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.
Structural studies[edit]
As of late 2007, 11 structures have been solved for this class of enzymes, with PDB accession codes 1EJ2, 1GZU, 1HYB, 1KKU, 1KQN, 1KQO, 1KR2, 1M8F, 1M8G, 1M8J, and 1M8K.
Isoform cellular localization[edit]
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[edit]
Chronic inflammation due to obesity and other causes reduced NMNAT and NAD+ levels in many tissues.[5]
References[edit]
- ^ a b c d Brazill JM, Li C, Zhu Y, Zhai RG (2017). "NMNAT: It's an NAD + Synthase… It's a Chaperone… It's a Neuroprotector". Current Opinion in Genetics & Development. 44: 156–162. doi:10.1016/j.gde.2017.03.014. PMC 5515290. PMID 28445802.
- ^ McReynolds MR, Chellappa L, Baur JA (2020). "Age-related NAD + Decline". Experimental Gerontology. 134: 110888. doi:10.1016/j.exger.2020.110888. PMC 7442590. PMID 32097708. S2CID 211237873.
- ^ Rajman L, Chwalek K, Sinclair DA (2018). "Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence". Cell Metabolism. 27 (3): 529–547. doi:10.1016/j.cmet.2018.02.011. PMC 6342515. PMID 29514064.
- ^ Hurtado-Bagès S, Knobloch G, Ladurner AG, Buschbeck M (2020). "The taming of PARP1 and its impact on NAD + metabolisme". Molecular Metabolism. 38: 100950. doi:10.1016/j.molmet.2020.01.014. PMC 7300387. PMID 32199820.
- ^ Yaku K, Okabe K, Nakagawa T (2018). "NAD metabolism: Implications in aging and longevity". Ageing Research Reviews. 47: 1–17. doi:10.1016/j.arr.2018.05.006. PMID 29883761. S2CID 47002665.
- ATKINSON MR, JACKSON JF, MORTON RK (1961). "Nicotinamide mononucleotide adenylyltransferase of pig-liver nuclei. The effects of nicotinamide mononucleotide concentration and pH on dinucleotide synthesis". Biochem. J. 80 (2): 318–23. doi:10.1042/bj0800318. PMC 1244001. PMID 13684981.
- Dahmen W, Webb B, Preiss J (1967). "The deamido-diphosphopyridine nucleotide and diphosphopyridine nucleotide pyrophosphorylases of Escherichia coli and yeast". Arch. Biochem. Biophys. 120 (2): 440–50. doi:10.1016/0003-9861(67)90262-7. PMID 4291828.
- Kornberg A; Pricer WE (1951). "Enzymatic cleavage of diphosphopyridine nucleotide with radioactive pyrophosphate". J. Biol. Chem. 191 (2): 535–541. doi:10.1016/S0021-9258(18)55958-5. PMID 14861199.
