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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2020-02-26 21:22:54 UTC
HMDB IDHMDB0001067
Secondary Accession Numbers
  • HMDB01067
Metabolite Identification
Common NameN-Acetylaspartylglutamic acid
DescriptionN-Acetylaspartylglutamate (NAAG) is a neuropeptide found in millimolar concentrations in the brain that is localized to subpopulations of glutamatergic, cholinergic, GABAergic, and noradrenergic neuronal systems. NAAG is released upon depolarization by a Ca(2+)-dependent process and is an agonist at mGluR3 receptors and an antagonist at NMDA receptors. NAAG is catabolized to N-acetylaspartate and glutamate primarily by glutamate carboxypeptidase II, which is expressed on the extracellular surface of astrocytes. The levels of NAAG and the activity of carboxypeptidase II are altered in a regionally specific fashion in several neuropsychiatric disorders (PMID: 9361299 ). N-Acetylaspartylglutamic acid (NAAG) is a purported precursor of N-acetylaspartic acid (NAA) and is present at about one-tenth of the concentration of NAA in the brain. NAAG has been reported to activate N-methyl-D-aspartic acid (NMDA) receptors in neurons. Previous immunohistochemical studies in the vertebrate central nervous system (CNS) have suggested that NAAG is exclusively localized to neurons. Recent evidence, however, indicates that NAAG might also be localized to nonneuronal cells within the CNS. Only traces of NAA and NAAG are detectable in other tissues. Some compounds can change levels of NAA and NAAG in the brain. For example, methylphenidate increases the levels of NAA and NAAG in the cerebral cortex; amphetamine also increases NAA concentration in a mature brain by 26%, raising the possibility that other neurochemical systems might be involved in the clinical effects of stimulants (PMID: 10603234 ).
Structure
Data?1582752174
Synonyms
ValueSource
IsospaglumateGenerator
N-Acetyl-L-alpha-aspartylglutamic acidMeSH
N-AcetylaspartylglutamateMeSH
N-Acetyl-aspartyl-glutamateMeSH
N-Acetyl-1-asp-gluMeSH
N-Acetyl-1-aspartylglutamic acidMeSH
N-(N-Acetyl-L-alpha-aspartyl)-L-glutamic acidMeSH
NaaxiaMeSH
NAAGAMeSH
N-Acetyl-aspartyl-glutamic acidMeSH
Acetyl-alpha-L-aspartylglutamic acidHMDB
Acetyl-α-L-aspartylglutamic acidHMDB
Isospaglumic acidHMDB
N-(N-Acetylaspartyl)glutamic acidHMDB
N-Acetyl-L-alpha-aspartyl-L-glutamic acidHMDB
N-Acetyl-L-aspartyl-L-glutamic acidHMDB
N-Acetyl-L-α-aspartyl-L-glutamic acidHMDB
N-Acetyl-alpha-L-aspartyl-L-glutamic acidHMDB
N-Acetyl-alpha-aspartylglutamic acidHMDB
N-Acetyl-α-L-aspartyl-L-glutamic acidHMDB
N-Acetyl-α-aspartylglutamic acidHMDB
N-Acetylaspartylglutamic acidHMDB
NAAGHMDB
alpha-Spaglumic acidHMDB
α-Spaglumic acidHMDB
Chemical FormulaC11H16N2O8
Average Molecular Weight304.255
Monoisotopic Molecular Weight304.090665483
IUPAC Name(2S)-2-[(2S)-3-carboxy-2-acetamidopropanamido]pentanedioic acid
Traditional NameN-acetylaspartylglutamic acid
CAS Registry Number3106-85-2
SMILES
CC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O
InChI Identifier
InChI=1S/C11H16N2O8/c1-5(14)12-7(4-9(17)18)10(19)13-6(11(20)21)2-3-8(15)16/h6-7H,2-4H2,1H3,(H,12,14)(H,13,19)(H,15,16)(H,17,18)(H,20,21)/t6-,7-/m0/s1
InChI KeyOPVPGKGADVGKTG-BQBZGAKWSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentDipeptides
Alternative Parents
Substituents
  • Alpha-dipeptide
  • Glutamic acid or derivatives
  • Aspartic acid or derivatives
  • N-acyl-l-alpha-amino acid
  • N-acyl-alpha-amino acid
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid amide
  • N-substituted-alpha-amino acid
  • Alpha-amino acid or derivatives
  • Tricarboxylic acid or derivatives
  • Fatty amide
  • N-acyl-amine
  • Fatty acyl
  • Acetamide
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Carboxylic acid
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxygen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Biological location:

Source:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility3.29 g/LALOGPS
logP-1.1ALOGPS
logP-2.3ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)3.13ChemAxon
pKa (Strongest Basic)-2ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area170.1 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity64.06 m³·mol⁻¹ChemAxon
Polarizability27.75 ųChemAxon
Number of Rings0ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0002-0900000000-2f2be5e8f2f3cf8bb047Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-001r-9600000000-b3b345b7a22f2cdfac08Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-001r-9000000000-20ed6fe2510cf8b50b0aSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableSpectrum
Biological Properties
Cellular LocationsNot Available
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Urine
Tissue Locations
  • Placenta
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified4.89 +/- 0.12 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified2.2 +/- 0.87 umol/mmol creatinineAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified3.42 (0.0-12.68) uMChildren (1-13 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified4.55 (0.7-8.4) uMAdult (>18 years old)BothNormal details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified2.35 +/- 1.08 umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified2.7 +/- 0.92 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
Cerebrospinal Fluid (CSF)Detected and Quantified16.37(3.55-37.30) uMChildren (1-13 years old)Not SpecifiedCanavan disease details
Cerebrospinal Fluid (CSF)Detected and Quantified43 (0.0-203.58) uMChildren (1-13 years old)Not SpecifiedPelizaeus Merzbacher Disease details
Cerebrospinal Fluid (CSF)Detected and Quantified18.7 (0.0-37.4) uMAdult (>18 years old)BothCanavan disease details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Colorectal cancer
details
UrineDetected and Quantified2.1 +/- 0.9 umol/mmol creatinineAdult (>18 years old)BothSchizophrenia details
Associated Disorders and Diseases
Disease References
Canavan disease
  1. Burlina AP, Ferrari V, Divry P, Gradowska W, Jakobs C, Bennett MJ, Sewell AC, Dionisi-Vici C, Burlina AB: N-acetylaspartylglutamate in Canavan disease: an adverse effector? Eur J Pediatr. 1999 May;158(5):406-9. [PubMed:10333125 ]
  2. Burlina AP, Ferrari V, Burlina AB, Ermani M, Boespflug-Tanguy O, Bertini E: N-acetylaspartylglutamate (NAAG) in Pelizaeus-Merzbacher disease. Adv Exp Med Biol. 2006;576:353-9; discussion 361-3. doi: 10.1007/0-387-30172-0_26. [PubMed:16802726 ]
Pelizaeus Merzbacher Disease
  1. Burlina AP, Ferrari V, Burlina AB, Ermani M, Boespflug-Tanguy O, Bertini E: N-acetylaspartylglutamate (NAAG) in Pelizaeus-Merzbacher disease. Adv Exp Med Biol. 2006;576:353-9; discussion 361-3. doi: 10.1007/0-387-30172-0_26. [PubMed:16802726 ]
Colorectal cancer
  1. Goedert JJ, Sampson JN, Moore SC, Xiao Q, Xiong X, Hayes RB, Ahn J, Shi J, Sinha R: Fecal metabolomics: assay performance and association with colorectal cancer. Carcinogenesis. 2014 Sep;35(9):2089-96. doi: 10.1093/carcin/bgu131. Epub 2014 Jul 18. [PubMed:25037050 ]
Schizophrenia
  1. Do KQ, Lauer CJ, Schreiber W, Zollinger M, Gutteck-Amsler U, Cuenod M, Holsboer F: gamma-Glutamylglutamine and taurine concentrations are decreased in the cerebrospinal fluid of drug-naive patients with schizophrenic disorders. J Neurochem. 1995 Dec;65(6):2652-62. [PubMed:7595563 ]
Associated OMIM IDs
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB022406
KNApSAcK IDNot Available
Chemspider ID164080
KEGG Compound IDC12270
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkN-Acetylaspartylglutamic acid
METLIN IDNot Available
PubChem Compound188803
PDB IDNot Available
ChEBI IDNot Available
Food Biomarker OntologyNot Available
VMH IDNot Available
References
Synthesis ReferenceMarchetti, Enzo; Mattalia, Gabriele; Curatolo, Francesco; Bergesi, Giuseppe. Structure and synthesis of the natural dipeptides N-acetyl-b-L-aspartyl-L-glutamic acid and its isomer N-acetyl-a-L-aspartyl-L-glutamic acid. Annali di Chimica (Rome, Italy) (1967), 57(6), 624-31.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Coyle JT: The nagging question of the function of N-acetylaspartylglutamate. Neurobiol Dis. 1997;4(3-4):231-8. [PubMed:9361299 ]
  2. Ma D, Zhang J, Sugahara K, Ageta T, Nakayama K, Kodama H: Simultaneous determination of N-acetylaspartic acid, N-acetylglutamic acid, and N-acetylaspartylglutamic acid in whole brain of 3-mercaptopropionic acid-treated rats using liquid chromatography-atmospheric pressure chemical ionization mass spectrometry. Anal Biochem. 1999 Dec 15;276(2):124-8. [PubMed:10603234 ]
  3. Elshenawy S, Pinney SE, Stuart T, Doulias PT, Zura G, Parry S, Elovitz MA, Bennett MJ, Bansal A, Strauss JF 3rd, Ischiropoulos H, Simmons RA: The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth. Int J Mol Sci. 2020 Feb 4;21(3). pii: ijms21031043. doi: 10.3390/ijms21031043. [PubMed:32033212 ]