NMNAT3

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Nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3) is an enzyme that in humans is encoded by the NMNAT3 gene. [1]

NMNAT3 is the third of three protein isoforms of nicotinamide-nucleotide adenylyltransferase (NMNAT) found in humans. [2] As with the other NMNATs, NMNAT3 is an enzyme that catalyzes nicotinamide adenine dinucleotide (NAD) synthesis. [2] NMNAT3 levels are highest in liver, heart, skeletal muscle, and erythrocytes. [2]

NMNAT3 is localized in mitochondria or cytoplasm, depending upon the cell type. [3] [4] [5] Knockdown of NMNAT3 gene expression in cell culture strongly reduces mitochondrial function. [4] NMNAT3 is essential for maintaining NAD in red blood cells. [4]

The catechin epigallocatechin gallate found in tea can activate NMNAT3 by more than 40%. [5]

As of 2024, mutations in the NMNAT3 gene have not been associated with any known human disease, [2] but NMNAT3 deficiency causes hemolytic anemia in mice. [6]

References

  1. ↑ Emanuelli M, Carnevali F, Saccucci F, Pierella F, Amici A, Raffaelli N, Magni G (Feb 2001). "Molecular cloning, chromosomal localization, tissue mRNA levels, bacterial expression, and enzymatic properties of human NMN adenylyltransferase". J Biol Chem. 276 (1): 406–12. doi: 10.1074/jbc.M008700200 . PMID   11027696.
  2. 1 2 3 4 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.
  3. ↑ Cambronne XA, Kraus WL (2020). "Location, Location, Location: Compartmentalization of NAD + Synthesis and Functions in Mammalian Cells". Trends in Biochemical Sciences . 45 (10): 858–873. doi:10.1016/j.tibs.2020.05.010. PMC   7502477 . PMID   32595066.
  4. 1 2 3 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.
  5. 1 2 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.
  6. ↑ Hikosaka, Keisuke; Ikutani, Masashi; Shito, Masayuki; Kazuma, Kohei; Gulshan, Maryam; Nagai, Yoshinori; Takatsu, Kiyoshi; Konno, Katsuhiro; Tobe, Kazuyuki; Kanno, Hitoshi; Nakagawa, Takashi (2014). "Deficiency of Nicotinamide Mononucleotide Adenylyltransferase 3 (Nmnat3) Causes Hemolytic Anemia by Altering the Glycolytic Flow in Mature Erythrocytes". Journal of Biological Chemistry. 289 (21): 14796–14811. doi: 10.1074/jbc.M114.554378 . PMC   4031534 . PMID   24739386.


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