Nicotinamide nucleotide adenylyl transferase
| Nicotinamide nucleotide adenylyl transferase | ||
|---|---|---|
|
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| Identifier | ||
| Gene name (s) | NMNAT1 , NMNAT2 , NMNAT3 | |
| Enzyme classification | ||
| EC, category | 2.7.7.1 , nucleotidyl transferase | |
| Response type | Transfer of an AMP molecule | |
| Substrate | Nicotinate / nicotinamide ribonucleotide + ATP | |
| Products | (Deamino-) NAD + + PP i | |
Nicotinamidmononukleotid adenylyltransferase (NMNAT) is the enzyme that the transfer of a molecule of adenosine monophosphate (AMP) at Nicotinamidmononukleotid (NMN) catalyzes . This is the final step in the biosynthesis of NAD . NMNAT is found in animals, bacteria, and some fungi. Most animals have two paralogous genes for this enzyme; humans and mice have three known, the translation products of which are located in different tissue types and cell compartments.
NMNAT isoforms
- NMNAT1 is found in the nucleoplasm of muscle , heart , liver , kidneys and brain as homohexamer. A zinc (II) ion serves as a cofactor, the enzyme has 279 amino acids ( UniProt Q9HAN9 ).
- NMNAT2 is detectable in large amounts in islet cells of Langerhans and in the brain and is probably localized as a monomer on the outside of the Golgi apparatus . The cofactor of the enzyme is magnesium and its length is 307 amino acids. Two isoforms are known ( UniProt Q9BZQ4 ).
- NMNAT3: Nothing is known about the tissue types where this enzyme is expressed. However, it seems to be localized in the cytosol and / or the mitochondria . It consists of 252 amino acids ( UniProt Q96T66 ).
Catalyzed reaction
+ + PP i
AMP (from ATP) is transferred to nicotinate ribonucleotide (NaMN), resulting in deamido-NAD + and diphosphate. Nicotinamide ribonucleotide (NMN) is also possible as a substrate.
More functions
There are indications of neuroprotective effects of NMNAT, which are independent of their enzyme function and indicate a role as a chaperone . NMNAT1 stimulates the activity of PARP-1 and binds to poly (ADP-ribose) .
Individual evidence
- ↑ Berger F, Lau C, Dahlmann M, Ziegler M: Subcellular compartmentation and differential catalytic properties of the three human nicotinamide mononucleotide adenylyltransferase isoforms . In: J. Biol. Chem. . 280, No. 43, October 2005, pp. 36334-41. doi : 10.1074 / jbc.M508660200 . PMID 16118205 .
- ↑ Sorci L, Cimadamore F, Scotti S, et al : Initial-rate kinetics of human NMN-adenylyltransferases: substrate and metal ion specificity, inhibition by products and multisubstrate analogues, and isozyme contributions to NAD + biosynthesis . In: Biochemistry . 46, No. 16, April 2007, pp. 4912-22. doi : 10.1021 / bi6023379 . PMID 17402747 .
- ↑ Zhai RG, Zhang F, Hiesinger PR, Cao Y, Haueter CM, Bellen HJ: NAD synthase NMNAT acts as a chaperone to protect against neurodegeneration . In: Nature . 452, No. 7189, April 2008, pp. 887-91. doi : 10.1038 / nature06721 . PMID 18344983 .
- ↑ Zhai RG, Cao Y, Hiesinger PR, et al : Drosophila NMNAT maintains neural integrity independent of its NAD synthesis activity . In: PLoS Biol . . 4, No. 12, November 2006, p. E416. doi : 10.1371 / journal.pbio.0040416 . PMID 17132048 . PMC 1665629 (free full text).
- ↑ Berger F, Lau C, Ziegler M: Regulation of poly (ADP-ribose) polymerase 1 activity by the phosphorylation state of the nuclear NAD biosynthetic enzyme NMN adenylyl transferase 1 . In: Proc. Natl. Acad. Sci. USA . 104, No. 10, March 2007, pp. 3765-70. doi : 10.1073 / pnas.0609211104 . PMID 17360427 . PMC 1820658 (free full text).
