Nicotinamide-nucleotide adenylyltransferase

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nicotinamide-nucleotide adenylyltransferase
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Nicotinamide-nucleotide adenylyltransferase (nuclear) hexamer, Human
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EC no. 2.7.7.1
CAS no. 9032-70-6
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In enzymology, nicotinamide-nucleotide adenylyltransferase (NMNAT) (EC 2.7.7.1) are enzymes that catalyzes the chemical reaction

Contents

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.[ citation needed ]

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]

Related Research Articles

<span class="mw-page-title-main">Nicotinamide adenine dinucleotide</span> Chemical compound which is reduced and oxidized

Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine nucleobase and the other, nicotinamide. NAD exists in two forms: an oxidized and reduced form, abbreviated as NAD+ and NADH (H for hydrogen), respectively.

<span class="mw-page-title-main">Nicotinamide adenine dinucleotide phosphate</span> Chemical compound

Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NADPH as a reducing agent ('hydrogen source'). NADPH is the reduced form, whereas NADP+ is the oxidized form. NADP+ is used by all forms of cellular life. NADP+ is essential for life because it is needed for cellular respiration.

<span class="mw-page-title-main">UTP—glucose-1-phosphate uridylyltransferase</span> Class of enzymes

UTP—glucose-1-phosphate uridylyltransferase also known as glucose-1-phosphate uridylyltransferase is an enzyme involved in carbohydrate metabolism. It synthesizes UDP-glucose from glucose-1-phosphate and UTP; i.e.,

<span class="mw-page-title-main">Ribose-phosphate diphosphokinase</span> Class of enzymes

Ribose-phosphate diphosphokinase is an enzyme that converts ribose 5-phosphate into phosphoribosyl pyrophosphate (PRPP). It is classified under EC 2.7.6.1.

NAD<sup>+</sup> kinase Enzyme

NAD+ kinase (EC 2.7.1.23, NADK) is an enzyme that converts nicotinamide adenine dinucleotide (NAD+) into NADP+ through phosphorylating the NAD+ coenzyme. NADP+ is an essential coenzyme that is reduced to NADPH primarily by the pentose phosphate pathway to provide reducing power in biosynthetic processes such as fatty acid biosynthesis and nucleotide synthesis. The structure of the NADK from the archaean Archaeoglobus fulgidus has been determined.

In enzymology, a rubredoxin-NAD+ reductase (EC 1.18.1.1) is an enzyme that catalyzes the chemical reaction.

<span class="mw-page-title-main">NAD(P)H dehydrogenase (quinone)</span>

In enzymology, a NAD(P)H dehydrogenase (quinone) (EC 1.6.5.2) is an enzyme that catalyzes the chemical reaction

In enzymology, a NAD+ synthetase (EC 6.3.1.5) is an enzyme that catalyzes the chemical reaction

In enzymology, a NAD+ diphosphatase (EC 3.6.1.22) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Nicotinamide phosphoribosyltransferase</span> Human protein and coding gene

Nicotinamide phosphoribosyltransferase, formerly known as pre-B-cell colony-enhancing factor 1 (PBEF1) or visfatin for its extracellular form (eNAMPT), is an enzyme that in humans is encoded by the NAMPT gene. The intracellular form of this protein (iNAMPT) is the rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD+) salvage pathway that converts nicotinamide to nicotinamide mononucleotide (NMN) which is responsible for most of the NAD+ formation in mammals. iNAMPT can also catalyze the synthesis of NMN from phosphoribosyl pyrophosphate (PRPP) when ATP is present. eNAMPT has been reported to be a cytokine (PBEF) that activates TLR4, that promotes B cell maturation, and that inhibits neutrophil apoptosis.

<span class="mw-page-title-main">Nicotinate-nucleotide diphosphorylase (carboxylating)</span> Class of enzymes

In enzymology, a nicotinate-nucleotide diphosphorylase (carboxylating) (EC 2.4.2.19) is an enzyme that catalyzes the chemical reaction

In enzymology, a FMN adenylyltransferase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Glucose-1-phosphate adenylyltransferase</span>

In enzymology, a glucose-1-phosphate adenylyltransferase is an enzyme that catalyzes the chemical reaction

In enzymology, a nicotinate-nucleotide adenylyltransferase (EC 2.7.7.18) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">NMNAT1</span> Protein-coding gene in the species Homo sapiens

Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) is an enzyme that in humans is encoded by the nmnat1 gene. It is a member of the nicotinamide-nucleotide adenylyltransferases (NMNATs) which catalyze nicotinamide adenine dinucleotide (NAD) synthesis.

<span class="mw-page-title-main">NMNAT2</span> Protein-coding gene in the species Homo sapiens

Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is an enzyme that in humans is encoded by the NMNAT2 gene.

<span class="mw-page-title-main">Nicotinamide riboside</span> Chemical compound

Nicotinamide riboside (NR, SR647) is a pyridine-nucleoside and a form of vitamin B3. It functions as a precursor to nicotinamide adenine dinucleotide, or NAD+, through a two-step and a three-step pathway.

The Nicotinamide Ribonucleoside (NR) Uptake Permease (PnuC) Family is a family of transmembrane transporters that is part of the TOG superfamily. Close PnuC homologues are found in a wide range of Gram-negative and Gram-positive bacteria, archaea and eukaryotes.

<span class="mw-page-title-main">Nicotinamide mononucleotide</span> Chemical compound

Nicotinamide mononucleotide is a nucleotide derived from ribose, nicotinamide, nicotinamide riboside and niacin. In humans, several enzymes use NMN to generate nicotinamide adenine dinucleotide (NADH). In mice, it has been proposed that NMN is absorbed via the small intestine within 10 minutes of oral uptake and converted to nicotinamide adenine dinucleotide (NAD+) through the Slc12a8 transporter. However, this observation has been challenged, and the matter remains unsettled.

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

References

  1. 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.
  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.


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