NMNAT3
Nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3) is an enzyme that in humans is encoded by the NMNAT3 gene.{{cite journal |vauthors=Emanuelli M, Carnevali F, Saccucci F, Pierella F, Amici A, Raffaelli N, Magni G | title = Molecular cloning, chromosomal localization, tissue mRNA levels, bacterial expression, and enzymatic properties of human NMN adenylyltransferase | journal = J Biol Chem | volume = 276 | issue = 1 | pages = 406–12 |date=Feb 2001 | pmid = 11027696 | doi = 10.1074/jbc.M008700200 | doi-access = free }}
NMNAT3 is the third of three protein isoforms of nicotinamide-nucleotide adenylyltransferase (NMNAT) found in humans.{{cite journal | vauthors = Brazill JM, Li C, Zhu Y, Zhai RG | title = NMNAT: It's an NAD + Synthase… It's a Chaperone… It's a Neuroprotector | journal = Current Opinion in Genetics & Development | volume = 44 | pages = 156–162 |date=2017 | doi = 10.1016/j.gde.2017.03.014 | pmc =5515290 | pmid = 28445802}} As with the other NMNATs, NMNAT3 is an enzyme that catalyzes nicotinamide adenine dinucleotide (NAD) synthesis. NMNAT3 levels are highest in liver, heart, skeletal muscle, and erythrocytes.
NMNAT3 is localized in mitochondria or cytoplasm, depending upon the cell type.{{cite journal | vauthors=Cambronne XA, Kraus WL | title=Location, Location, Location: Compartmentalization of NAD + Synthesis and Functions in Mammalian Cells | journal= Trends in Biochemical Sciences | volume=45 | issue=10 | pages=858–873 | year=2020 | url=https://www.jbc.org/content/294/52/19831.long | doi = 10.1016/j.tibs.2020.05.010 | pmc=7502477 | pmid=32595066}}{{cite journal | vauthors = Yaku K, Okabe K, Nakagawa T | s2cid = 47002665 | title = NAD Metabolism: Implications in Aging and Longevity | journal = Ageing Research Reviews | volume = 47 | pages = 1–17 |date=2018 | doi = 10.1016/j.arr.2018.05.006 | pmid = 29883761}}{{cite journal | vauthors = Rajman L, Chwalek K, Sinclair DA | title = Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence | journal = Cell Metabolism | volume = 27 | issue=3 | pages = 529–547 |date=2018 | doi = 10.1016/j.cmet.2018.02.011 | pmc =6342515 | pmid = 29514064}} Knockdown of NMNAT3 gene expression in cell culture strongly reduces mitochondrial function. NMNAT3 is essential for maintaining NAD in red blood cells.
The catechin epigallocatechin gallate found in tea can activate NMNAT3 by more than 40%.
As of 2024, mutations in the NMNAT3 gene have not been associated with any known human disease, but NMNAT3 deficiency causes hemolytic anemia in mice.{{Cite journal |last1=Hikosaka |first1=Keisuke |last2=Ikutani |first2=Masashi |last3=Shito |first3=Masayuki |last4=Kazuma |first4=Kohei |last5=Gulshan |first5=Maryam |last6=Nagai |first6=Yoshinori |last7=Takatsu |first7=Kiyoshi |last8=Konno |first8=Katsuhiro |last9=Tobe |first9=Kazuyuki |last10=Kanno |first10=Hitoshi |last11=Nakagawa |first11=Takashi |date=2014 |title=Deficiency of Nicotinamide Mononucleotide Adenylyltransferase 3 (Nmnat3) Causes Hemolytic Anemia by Altering the Glycolytic Flow in Mature Erythrocytes |journal=Journal of Biological Chemistry |language=en |volume=289 |issue=21 |pages=14796–14811 |doi=10.1074/jbc.M114.554378 |doi-access=free |pmc=4031534 |pmid=24739386}}