NP-MRD: Showing NP-Card for N-Acetyl-L-aspartic acid (NP0000081)

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Record Information

Version

2.0

Created at

2005-11-16 15:48:42 UTC

Updated at

2021-08-09 22:33:30 UTC

NP-MRD ID

NP0000081

Secondary Accession Numbers

None

Natural Product Identification

Common Name

N-Acetyl-L-aspartic acid

Description

N-Acetyl-L-Aspartic acid (NAA) or N-Acetylaspartic acid, belongs to the class of organic compounds known as N-acyl-alpha amino acids. N-acyl-alpha amino acids are compounds containing an alpha amino acid which bears an acyl group at its terminal nitrogen atom. N-alpha-Acetyl-L-aspartic acid can also be classified as an alpha amino acid or a derivatized alpha amino acid. Technically, N-Acetyl-L-aspartic acid is a biologically available N-terminal capped form of the proteinogenic alpha amino acid L-aspartic acid. N-acetyl amino acids can be produced either via direct synthesis of specific N-acetyltransferases or via the proteolytic degradation of N-acetylated proteins by specific hydrolases. N-terminal acetylation of proteins is a widespread and highly conserved process in eukaryotes that is involved in protection and stability of proteins (PMID: 16465618 ). About 85% of all human proteins and 68% of all yeast proteins are acetylated at their N-terminus (PMID: 21750686 ). Several proteins from prokaryotes and archaea are also modified by N-terminal acetylation. The majority of eukaryotic N-terminal-acetylation reactions occur through N-acetyltransferase enzymes or NAT’s (PMID: 30054468 ). These enzymes consist of three main oligomeric complexes NatA, NatB, and NatC, which are composed of at least a unique catalytic subunit and one unique ribosomal anchor. The substrate specificities of different NAT enzymes are mainly determined by the identities of the first two N-terminal residues of the target protein. The human NatA complex co-translationally acetylates N-termini that bear a small amino acid (A, S, T, C, and occasionally V and G) (PMID: 30054468 ). NatA also exists in a monomeric state and can post-translationally acetylate acidic N-termini residues (D-, E-). NatB and NatC acetylate N-terminal methionine with further specificity determined by the identity of the second amino acid. N-acetylated amino acids, such as N-acetylaspartate can be released by an N-acylpeptide hydrolase from peptides generated by proteolytic degradation (PMID: 16465618 ). In addition to the NAT enzymes and protein-based acetylation, N-acetylation of free aspartic acid can also occur. In particular, N-Acetyl-L-aspartic acid can be synthesized in neurons from the amino acid aspartate and acetyl coenzyme A (acetyl CoA). Specifically, the enzyme known as aspartate N-acetyltransferase (EC 2.3.1.17) Catalyzes the transfer of the acetyl group of acetyl CoA to the amino group of aspartate. N-Acetyl-L-aspartic acid is the second most concentrated molecule in the brain after the amino acid glutamate. The various functions served by N-acetylaspartic acid are still under investigation, but the primary proposed functions include (1) acting as a neuronal osmolyte that is involved in fluid balance in the brain, (2) serving as a source of acetate for lipid and myelin synthesis in oligodendrocytes (the glial cells that myelinate neuronal axons), (3) serving as a precursor for the synthesis of the important dipeptide neurotransmitter N-acetylaspartylglutamate (NAAG), and (4) playing a potential role in energy production from the amino acid glutamate in neuronal mitochondria. High neurotransmitter (i.E. N-acetylaspartic acid) levels can lead to abnormal neural signaling, delayed or arrested intellectual development, and difficulties with general motor skills. When present in sufficiently high levels, N-acetylaspartic acid can be a neurotoxin, an acidogen, and a metabotoxin. A neurotoxin is a compound that disrupts or attacks neural tissue. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of N-acetylaspartic acid are associated with Canavan disease. Because N-acetylaspartic acid functions as an organic acid and high levels of organic acids can lead to a condition known as acidosis. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. Infants with acidosis have symptoms that include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart abnormalities, seizures, coma, and possibly death. Many affected children with organic acidemias experience intellectual disability or delayed development. In adults, acidosis or acidemia is characterized by headaches, confusion, feeling tired, tremors, sleepiness, and flapping tremors. Many N-acetylamino acids, including N-acetylaspartic acid, are classified as uremic toxins if present in high abundance in the serum or plasma (PMID: 26317986 ; PMID: 20613759 ). Uremic toxins are a diverse group of endogenously produced molecules that, if not properly cleared or eliminated by the kidneys, can cause kidney damage, cardiovascular disease and neurological deficits (PMID: 18287557 ).

Structure

MOL 3D MOL SDF 3D SDF PDB 3D PDB SMILES InChI

HEADER    PROTEIN                                 27-MAY-19   NONE
TITLE     NULL                                                        
COMPND    MOLECULE:                                                   
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   27-MAY-19         0                                  
HETATM    1  C   UNK     0    8667.3338665.899   0.000  0.00  0.00           C+0
HETATM    2  C   UNK     0    8666.0008665.127   0.000  0.00  0.00           C+0
HETATM    3  C   UNK     0    8664.6678665.899   0.000  0.00  0.00           C+0
HETATM    4  O   UNK     0    8663.3338665.127   0.000  0.00  0.00           O+0
HETATM    5  O   UNK     0    8664.6678667.436   0.000  0.00  0.00           O+0
HETATM    6  N   UNK     0    8667.3338667.436   0.000  0.00  0.00           N+0
HETATM    7  C   UNK     0    8668.6688668.206   0.000  0.00  0.00           C+0
HETATM    8  C   UNK     0    8670.0008667.436   0.000  0.00  0.00           C+0
HETATM    9  O   UNK     0    8668.6688669.746   0.000  0.00  0.00           O+0
HETATM   10  C   UNK     0    8668.6688665.127   0.000  0.00  0.00           C+0
HETATM   11  O   UNK     0    8670.0008665.899   0.000  0.00  0.00           O+0
HETATM   12  O   UNK     0    8668.6688663.587   0.000  0.00  0.00           O+0
CONECT    1    2    6   10                                                  
CONECT    2    1    3                                                       
CONECT    3    2    4    5                                                  
CONECT    4    3                                                            
CONECT    5    3                                                            
CONECT    6    1    7                                                       
CONECT    7    6    8    9                                                  
CONECT    8    7                                                            
CONECT    9    7                                                            
CONECT   10    1   11   12                                                  
CONECT   11   10                                                            
CONECT   12   10                                                            
MASTER        0    0    0    0    0    0    0    0   12    0   22    0
END

View in JSmol

Synonyms

Value	Source
(S)-2-(Acetylamino)butanedioic acid	ChEBI
(S)-2-(Acetylamino)succinic acid	ChEBI
Acetyl-L-aspartic acid	ChEBI
Acetylaspartic acid	ChEBI
L-N-Acetylaspartic acid	ChEBI
N-Acetylaspartic acid	ChEBI
NAA	ChEBI
(S)-2-(Acetylamino)butanedioate	Generator
(S)-2-(Acetylamino)succinate	Generator
Acetyl-L-aspartate	Generator
Acetylaspartate	Generator
L-N-Acetylaspartate	Generator
N-Acetylaspartate	Generator
N-Acetyl-L-aspartate	Generator
(2S)-2-Acetamidobutanedioate	HMDB
(2S)-2-Acetamidobutanedioic acid	HMDB
N-Acetyl-S-aspartate	HMDB
N-Acetyl-S-aspartic acid	HMDB
N-Acetyl aspartate	HMDB
N-Acetylaspartate, monopotassium salt	HMDB
Acetyl aspartic acid	HMDB

Chemical Formula

C₆H₉NO₅

Average Mass

175.1394 Da

Monoisotopic Mass

175.04807 Da

IUPAC Name

(2S)-2-acetamidobutanedioic acid

Traditional Name

acetyl-L-aspartic acid

CAS Registry Number

997-55-7

SMILES

CC(=O)N[C@@H](CC(O)=O)C(O)=O

InChI Identifier

InChI=1S/C6H9NO5/c1-3(8)7-4(6(11)12)2-5(9)10/h4H,2H2,1H3,(H,7,8)(H,9,10)(H,11,12)/t4-/m0/s1

InChI Key

OTCCIMWXFLJLIA-BYPYZUCNSA-N

Experimental Spectra

Spectrum Type	Description	Depositor Email	Depositor Organization	Depositor	Deposition Date	View
1D NMR	¹H NMR Spectrum (1D, 500 MHz, H₂O, experimental)	Wishart Lab	Wishart Lab	David Wishart	2021-06-20	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, H₂O, experimental)	Wishart Lab	Wishart Lab	David Wishart	2021-06-20	View Spectrum

Predicted Spectra

Not Available

Chemical Shift Submissions

Spectrum Type	Description	Depositor Email	Depositor Organization	Depositor	Deposition Date	View
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, H₂O, simulated)	v.dorna83@yahoo.com	Not Available	Not Available	2021-07-21	View Spectrum

Species

Species of Origin

Species Name	Source	Reference
Anas platyrhynchos	FooDB	FooDB
Anatidae	FooDB	FooDB
Anser anser	FooDB	FooDB
Bison bison	FooDB	FooDB
Bos taurus	FooDB	FooDB
Bos taurus X Bison bison	FooDB	FooDB
Bubalus bubalis	FooDB	FooDB
Capra aegagrus hircus	FooDB	FooDB
Cervidae	FooDB	FooDB
Cervus canadensis	FooDB	FooDB
Columba	FooDB	FooDB
Columbidae	FooDB	FooDB
Dromaius novaehollandiae	FooDB	FooDB
Equus caballus	FooDB	FooDB
Gallus gallus	FooDB	FooDB
Homo sapiens	LOTUS Database	35616633
Homo sapiens (Urine)	Animalia	KNApSAcK
Lagopus muta	FooDB	FooDB
Leporidae	FooDB	FooDB
Lepus timidus	FooDB	FooDB
Melanitta fusca	FooDB	FooDB
Meleagris gallopavo	FooDB	FooDB
Numida meleagris	FooDB	FooDB
Odocoileus	FooDB	FooDB
Oryctolagus	FooDB	FooDB
Ovis aries	FooDB	FooDB
Phasianidae	FooDB	FooDB
Phasianus colchicus	FooDB	FooDB
Struthio camelus	FooDB	FooDB
Sus scrofa	FooDB	FooDB
Sus scrofa domestica	FooDB	FooDB

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as aspartic acid and derivatives. Aspartic acid and derivatives are compounds containing an aspartic acid or a derivative thereof resulting from reaction of aspartic acid at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Aspartic acid and derivatives

Alternative Parents

Substituents

Aspartic acid or derivatives
N-acyl-alpha-amino acid
N-acyl-alpha amino acid or derivatives
N-acyl-l-alpha-amino acid
Dicarboxylic acid or derivatives
Fatty acid
Acetamide
Carboxamide group
Secondary carboxylic acid amide
Carboxylic acid
Carbonyl group
Organooxygen compound
Organonitrogen compound
Organopnictogen compound
Organic oxygen compound
Organic nitrogen compound
Organic oxide
Hydrocarbon derivative
Aliphatic acyclic compound

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

N-acetyl-L-amino acid (CHEBI:21547 )
N-acyl-L-aspartic acid (CHEBI:21547 )

Physical Properties

State

Solid

Experimental Properties

Property	Value	Reference
Melting Point	137 - 140 °C	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	675 mg/mL	Not Available
LogP	Not Available	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	21.1 g/L	ALOGPS
logP	-0.79	ALOGPS
logP	-1.4	ChemAxon
logS	-0.92	ALOGPS
pKa (Strongest Acidic)	3.41	ChemAxon
pKa (Strongest Basic)	-2	ChemAxon
Physiological Charge	-2	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	103.7 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	35.98 m³·mol⁻¹	ChemAxon
Polarizability	15.29 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

External Links

HMDB ID

HMDB0000812

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FoodDB ID

FDB022260

KNApSAcK ID

Not Available

Chemspider ID

KEGG Compound ID

BioCyc ID

BiGG ID

Wikipedia Link

N-acetylaspartic_acid

METLIN ID

5776

PubChem Compound

65065

PDB ID

Not Available

ChEBI ID

21547

Good Scents ID

rw1408501

References

General References

Kaul R, Gao GP, Balamurugan K, Matalon R: Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease. Nat Genet. 1993 Oct;5(2):118-23. [PubMed:8252036 ]
Wevers RA, Engelke U, Wendel U, de Jong JG, Gabreels FJ, Heerschap A: Standardized method for high-resolution 1H-NMR of cerebrospinal fluid. Clin Chem. 1995 May;41(5):744-51. [PubMed:7729054 ]
Tedeschi G, Bonavita S, Banerjee TK, Virta A, Schiffmann R: Diffuse central neuronal involvement in Fabry disease: a proton MRS imaging study. Neurology. 1999 May 12;52(8):1663-7. [PubMed:10331696 ]
Tacke U, Olbrich H, Sass JO, Fekete A, Horvath J, Ziyeh S, Kleijer WJ, Rolland MO, Fisher S, Payne S, Vargiami E, Zafeiriou DI, Omran H: Possible genotype-phenotype correlations in children with mild clinical course of Canavan disease. Neuropediatrics. 2005 Aug;36(4):252-5. [PubMed:16138249 ]
Rocca MA, Mezzapesa DM, Falini A, Ghezzi A, Martinelli V, Scotti G, Comi G, Filippi M: Evidence for axonal pathology and adaptive cortical reorganization in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis. Neuroimage. 2003 Apr;18(4):847-55. [PubMed:12725761 ]
Izumiyama H, Abe T, Tanioka D, Fukuda A, Kunii N: Clinicopathological examination of glioma by proton magnetic resonance spectroscopy background. Brain Tumor Pathol. 2004;21(1):39-46. [PubMed:15696968 ]
Bal D, Gryff-Keller A, Gradowska W: Absolute configuration of N-acetylaspartate in urine from patients with Canavan disease. J Inherit Metab Dis. 2005;28(4):607-9. [PubMed:15902566 ]
Manji HK, Moore GJ, Chen G: Clinical and preclinical evidence for the neurotrophic effects of mood stabilizers: implications for the pathophysiology and treatment of manic-depressive illness. Biol Psychiatry. 2000 Oct 15;48(8):740-54. [PubMed:11063971 ]
Vermathen P, Laxer KD, Matson GB, Weiner MW: Hippocampal structures: anteroposterior N-acetylaspartate differences in patients with epilepsy and control subjects as shown with proton MR spectroscopic imaging. Radiology. 2000 Feb;214(2):403-10. [PubMed:10671587 ]
Clementi V, Tonon C, Lodi R, Malucelli E, Barbiroli B, Iotti S: Assessment of glutamate and glutamine contribution to in vivo N-acetylaspartate quantification in human brain by (1)H-magnetic resonance spectroscopy. Magn Reson Med. 2005 Dec;54(6):1333-9. [PubMed:16265633 ]
Surendran S, Matalon KM, Szucs S, Tyring SK, Matalon R: Metabolic changes in the knockout mouse for Canavan's disease: implications for patients with Canavan's disease. J Child Neurol. 2003 Sep;18(9):611-5. [PubMed:14572139 ]
Gordon N: Canavan disease: a review of recent developments. Eur J Paediatr Neurol. 2001;5(2):65-9. [PubMed:11589315 ]
Zhu XH, Chen W: Observed BOLD effects on cerebral metabolite resonances in human visual cortex during visual stimulation: a functional (1)H MRS study at 4 T. Magn Reson Med. 2001 Nov;46(5):841-7. [PubMed:11675633 ]
Lam WW, Wang ZJ, Zhao H, Berry GT, Kaplan P, Gibson J, Kaplan BS, Bilaniuk LT, Hunter JV, Haselgrove JC, Zimmermann RA: 1H MR spectroscopy of the basal ganglia in childhood: a semiquantitative analysis. Neuroradiology. 1998 May;40(5):315-23. [PubMed:9638674 ]
Martin RC, Sawrie S, Hugg J, Gilliam F, Faught E, Kuzniecky R: Cognitive correlates of 1H MRSI-detected hippocampal abnormalities in temporal lobe epilepsy. Neurology. 1999 Dec 10;53(9):2052-8. [PubMed:10599780 ]
Trope I, Lopez-Villegas D, Lenkinski RE: Magnetic resonance imaging and spectroscopy of regional brain structure in a 10-year-old boy with elevated blood lead levels. Pediatrics. 1998 Jun;101(6):E7. [PubMed:9606249 ]
Kvittingen EA, Guldal G, Borsting S, Skalpe IO, Stokke O, Jellum E: N-acetylaspartic aciduria in a child with a progressive cerebral atrophy. Clin Chim Acta. 1986 Aug 15;158(3):217-27. [PubMed:3769199 ]
Gideon P, Henriksen O, Sperling B, Christiansen P, Olsen TS, Jorgensen HS, Arlien-Soborg P: Early time course of N-acetylaspartate, creatine and phosphocreatine, and compounds containing choline in the brain after acute stroke. A proton magnetic resonance spectroscopy study. Stroke. 1992 Nov;23(11):1566-72. [PubMed:1440704 ]
Van Damme P, Hole K, Pimenta-Marques A, Helsens K, Vandekerckhove J, Martinho RG, Gevaert K, Arnesen T: NatF contributes to an evolutionary shift in protein N-terminal acetylation and is important for normal chromosome segregation. PLoS Genet. 2011 Jul;7(7):e1002169. doi: 10.1371/journal.pgen.1002169. Epub 2011 Jul 7. [PubMed:21750686 ]

Showing NP-Card for N-Acetyl-L-aspartic acid (NP0000081)

MOL for NP0000081 (N-Acetyl-L-aspartic acid)

3D MOL for NP0000081 (N-Acetyl-L-aspartic acid)

3D SDF for NP0000081 (N-Acetyl-L-aspartic acid)

3D-SDF for NP0000081 (N-Acetyl-L-aspartic acid)

PDB for NP0000081 (N-Acetyl-L-aspartic acid)

3D PDB for NP0000081 (N-Acetyl-L-aspartic acid)

SMILES for NP0000081 (N-Acetyl-L-aspartic acid)

INCHI for NP0000081 (N-Acetyl-L-aspartic acid)

Structure for NP0000081 (N-Acetyl-L-aspartic acid)

3D Structure for NP0000081 (N-Acetyl-L-aspartic acid)