Nicotinamide-nucleotide adenylyltransferase

In enzymology, nicotinamide-nucleotide adenylyltransferase (NMNAT) (EC 2.7.7.1) are enzymes that catalyzes the chemical reaction

ATP + nicotinamide mononucleotide diphosphate + NAD+
nicotinamide-nucleotide adenylyltransferase
Nicotinamide-nucleotide adenylyltransferase (nuclear) hexamer, Human
Identifiers
EC number2.7.7.1
CAS number9032-70-6
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

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.

Structural studies

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

The three protein isoforms have the following cellular localizations[3]

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]

References
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.


This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.