Tmic
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Record Information
Version2.0
Creation Date2014-08-29 06:08:19 UTC
Update Date2018-03-21 17:46:12 UTC
Accession NumberT3D4259
Identification
Common NameAminoadipic acid
ClassSmall Molecule
DescriptionAminoadipic acid (2-aminoadipate) is a metabolite in the principal biochemical pathway of lysine. It is an intermediate in the metabolism (i.e. breakdown or degradation) of lysine and saccharopine. It antagonizes neuroexcitatory activity modulated by the glutamate receptor N-methyl-D-aspartate (NMDA). Aminoadipic acid has also been shown to inhibit the production of kynurenic acid, a broad spectrum excitatory amino acid receptor antagonist, in brain tissue slices (PMID: 8566117). Recent studies have shown that aminoadipic acid is elevated in prostate biopsy tissues from prostate cancer patients (PMID: 23737455). Mutations in DHTKD1 (dehydrogenase E1 and transketolase domain-containing protein 1) have been shown to cause human 2-aminoadipic aciduria and 2-oxoadipic aciduria via impaired decarboxylation of 2-oxoadipate to glutaryl-CoA, which is the last step in the lysine degradation pathway (PMID: 23141293). Aging, diabetes, sepsis, and renal failure are known to catalyze the oxidation of lysyl residues to form 2-aminoadipic acid in human skin collagen and potentially other tissues (PMID: 18448817). Proteolytic breakdown of these tissues can lead to the release of free 2-aminoadipic acid. Studies in rats indicate that aminoadipic acid (along with the three branched-chain amino acids - leucine, valine, and isoleucine) levels are elevated in the pre-diabetic phase and so aminoadipic acid may serve as a predictive biomarker for the development of diabetes (PMID: 15389298). Long-term hyperglycemia of endothelial cells can also lead to elevated levels of aminoadipate which is thought to be a sign of lysine breakdown through oxidative stress and reactive oxygen species (ROS) (PMID: 21961526). 2-Aminoadipate is a potential small-molecule marker of oxidative stress (PMID: 21647514). Therefore, depending on the circumstances aminoadipic acid can act as an acidogen, a diabetogen, an atherogen and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A diabetogen is a compound that can lead to type 2 diabetes. An atherogen is a compound that leads to atherosclerosis and cardiovascular disease. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of aminoadipic acid are associated with at least two inborn errors of metabolism including, 2-aminoadipic aciduria and 2-oxoadipic aciduria. Aminoadipic acid is an organic acid and 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. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart abnormalities, kidney abnormalities, liver damage, seizures, coma, and possibly death. These are also the characteristic symptoms of the untreated IEMs mentioned above. 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 seizures. As a diabetogen, serum aminoadipic levels appear to regulate glucose homeostasis and have been highly predictive of individuals who later develop diabetes (PMID: 24091325). In particular, aminoadipic acid lowers fasting plasma glucose levels and enhances insulin secretion from human islets. As an atherogen, aminoadipic acid has been found to be produced at high levels via protein lysine oxidation in atherosclerotic plaques (PMID: 28069522).
Compound Type
  • Amine
  • Animal Toxin
  • Food Toxin
  • Industrial/Workplace Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+/-)-2-Aminoadipate
(+/-)-2-Aminoadipic acid
2-Aminoadipate
2-Aminoadipic acid
a-Aminoadipate
a-Aminoadipic acid
alpha-Amino-adipic acid
alpha-Aminoadipate
alpha-Aminoadipic acid
Aminoadipate
DL-2-Aminoadipate
DL-2-Aminoadipic acid
DL-2-Aminohexanedioate
DL-2-Aminohexanedioic acid
DL-a-Aminoadipate
DL-a-Aminoadipic acid
DL-alpha-Aminoadipate
DL-alpha-Aminoadipic acid
L-2-Aminoadipate
L-2-Aminoadipic acid
L-2-Aminohexanedioate
L-2-Aminohexanedioic acid
L-alpha-Aminoadipate
L-alpha-Aminoadipic acid
Chemical FormulaC6H11NO4
Average Molecular Mass161.156 g/mol
Monoisotopic Mass161.069 g/mol
CAS Registry Number542-32-5
IUPAC Name2-aminohexanedioic acid
Traditional Nameaminoadipic acid
SMILESNC(CCCC(O)=O)C(O)=O
InChI IdentifierInChI=1/C6H11NO4/c7-4(6(10)11)2-1-3-5(8)9/h4H,1-3,7H2,(H,8,9)(H,10,11)
InChI KeyInChIKey=OYIFNHCXNCRBQI-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as alpha amino acids. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon).
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acids
Alternative Parents
Substituents
  • Alpha-amino acid
  • Medium-chain fatty acid
  • Amino fatty acid
  • Dicarboxylic acid or derivatives
  • Fatty acid
  • Fatty acyl
  • Amino acid
  • Carboxylic acid
  • Organic oxide
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Organopnictogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Amine
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Membrane
  • Mitochondria
Biofluid LocationsNot Available
Tissue Locations
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Lysine DegradationSMP00037 map00310
2-aminoadipic 2-oxoadipic aciduriaSMP00719 Not Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point196 - 198°C
Boiling PointNot Available
Solubility2.2 mg/mL
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility32.7 g/LALOGPS
logP-3.4ALOGPS
logP-2.8ChemAxon
logS-0.69ALOGPS
pKa (Strongest Acidic)2.01ChemAxon
pKa (Strongest Basic)9.53ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area100.62 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity35.89 m³·mol⁻¹ChemAxon
Polarizability15.53 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-02di-0950000000-ec4fd991a53a8b6bc6aeView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-02di-0950000000-ec4fd991a53a8b6bc6aeView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00r6-9300000000-9ef33042820e032c1af3View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00ri-9620000000-052fe671da5a64787657View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-03xv-2900000000-58b4f0b3e06cbb7abb90View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0a4j-9000000000-cc9c0c03f7c3890b531cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0a4i-9000000000-7b74167f01c922da9ef7View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0002-9400000000-71832a0d1e49341749a7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00kg-2900000000-3e45ac769d3b229221a3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01ba-9600000000-c51318834cc371625d46View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05fu-9000000000-edbc970f12ea186bcf06View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-1900000000-0f7002659f604cc69395View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01ox-4900000000-bf42ddc971a2a05516a2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0abc-9100000000-1979c27463bab7d33d58View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesThis is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.
Minimum Risk LevelNot Available
Health EffectsChronically high levels of aminoadipic acid are associated with at least 2 inborn errors of metabolism including: : 2-aminoadipic and 2-oxoadipic aciduria.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB00510
PubChem Compound ID469
ChEMBL IDCHEMBL433238
ChemSpider ID456
KEGG IDC00956
UniProt IDNot Available
OMIM ID
ChEBI ID37024
BioCyc IDCPD-468
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia Linkalpha-Aminoadipate
References
Synthesis ReferenceKhan, Naseem H.; Ali, Mohd.; Panda, H.; Rakhshinda. Synthesis of a-aminoadipic acid. Journal of the Indian Chemical Society (1982), 59(9), 1077-8.
MSDSLink
General References
  1. Wu HQ, Ungerstedt U, Schwarcz R: L-alpha-aminoadipic acid as a regulator of kynurenic acid production in the hippocampus: a microdialysis study in freely moving rats. Eur J Pharmacol. 1995 Jul 25;281(1):55-61. [8566117 ]
  2. Jung K, Reszka R, Kamlage B, Bethan B, Stephan C, Lein M, Kristiansen G: Tissue metabolite profiling identifies differentiating and prognostic biomarkers for prostate carcinoma. Int J Cancer. 2013 Dec 15;133(12):2914-24. doi: 10.1002/ijc.28303. Epub 2013 Jun 29. [23737455 ]
  3. Danhauser K, Sauer SW, Haack TB, Wieland T, Staufner C, Graf E, Zschocke J, Strom TM, Traub T, Okun JG, Meitinger T, Hoffmann GF, Prokisch H, Kolker S: DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria. Am J Hum Genet. 2012 Dec 7;91(6):1082-7. doi: 10.1016/j.ajhg.2012.10.006. Epub 2012 Nov 8. [23141293 ]
  4. Sell DR, Strauch CM, Shen W, Monnier VM: Aging, diabetes, and renal failure catalyze the oxidation of lysyl residues to 2-aminoadipic acid in human skin collagen: evidence for metal-catalyzed oxidation mediated by alpha-dicarbonyls. Ann N Y Acad Sci. 2008 Apr;1126:205-9. doi: 10.1196/annals.1433.065. [18448817 ]
  5. Wijekoon EP, Skinner C, Brosnan ME, Brosnan JT: Amino acid metabolism in the Zucker diabetic fatty rat: effects of insulin resistance and of type 2 diabetes. Can J Physiol Pharmacol. 2004 Jul;82(7):506-14. [15389298 ]
  6. Yuan W, Zhang J, Li S, Edwards JL: Amine metabolomics of hyperglycemic endothelial cells using capillary LC-MS with isobaric tagging. J Proteome Res. 2011 Nov 4;10(11):5242-50. doi: 10.1021/pr200815c. Epub 2011 Oct 17. [21961526 ]
  7. Zeitoun-Ghandour S, Leszczyszyn OI, Blindauer CA, Geier FM, Bundy JG, Sturzenbaum SR: C. elegans metallothioneins: response to and defence against ROS toxicity. Mol Biosyst. 2011 Aug;7(8):2397-406. doi: 10.1039/c1mb05114h. Epub 2011 Jun 7. [21647514 ]
  8. Brauner-Osborne H, Slok FA, Skjaerbaek N, Ebert B, Sekiyama N, Nakanishi S, Krogsgaard-Larsen P: A new highly selective metabotropic excitatory amino acid agonist: 2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid. J Med Chem. 1996 Aug 2;39(16):3188-94. [8759641 ]
  9. Hori S: [Pathophysiology of intraocular neovascularization]. Nihon Ganka Gakkai Zasshi. 1990 Dec;94(12):1103-21. [1707214 ]
  10. Ouwerkerk-Mahadevan S, Mulder GJ: Inhibition of glutathione conjugation in the rat in vivo by analogues of glutathione conjugates. Chem Biol Interact. 1998 Apr 24;111-112:163-76. [9679552 ]
  11. Mechanic GL: The qualitative and quantitative crosslink chemistry of collagen matrices. Adv Exp Med Biol. 1977;86B:699-708. [20755 ]
  12. Fiermonte G, Dolce V, Palmieri L, Ventura M, Runswick MJ, Palmieri F, Walker JE: Identification of the human mitochondrial oxodicarboxylate carrier. Bacterial expression, reconstitution, functional characterization, tissue distribution, and chromosomal location. J Biol Chem. 2001 Mar 16;276(11):8225-30. Epub 2000 Nov 16. [11083877 ]
  13. Okuno E, Tsujimoto M, Nakamura M, Kido R: 2-Aminoadipate-2-oxoglutarate aminotransferase isoenzymes in human liver: a plausible physiological role in lysine and tryptophan metabolism. Enzyme Protein. 1993;47(3):136-48. [8087205 ]
  14. Takechi T, Okada T, Wakiguchi H, Morita H, Kurashige T, Sugahara K, Kodama H: Identification of N-acetyl-alpha-aminoadipic acid in the urine of a patient with alpha-aminoadipic and alpha-ketoadipic aciduria. J Inherit Metab Dis. 1993;16(1):119-26. [8487492 ]
  15. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [19212411 ]
  16. Sell DR, Strauch CM, Shen W, Monnier VM: 2-aminoadipic acid is a marker of protein carbonyl oxidation in the aging human skin: effects of diabetes, renal failure and sepsis. Biochem J. 2007 Jun 1;404(2):269-77. [17313367 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Glutamate receptor activity
Specific Function:
G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling activates a phosphatidylinositol-calcium second messenger system. May participate in the central action of glutamate in the CNS, such as long-term potentiation in the hippocampus and long-term depression in the cerebellum.
Gene Name:
GRM1
Uniprot ID:
Q13255
Molecular Weight:
132355.855 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>1000 uMNot AvailableBindingDB 50052553
References
  1. Brauner-Osborne H, Egebjerg J, Nielsen EO, Madsen U, Krogsgaard-Larsen P: Ligands for glutamate receptors: design and therapeutic prospects. J Med Chem. 2000 Jul 13;43(14):2609-45. [10893301 ]
General Function:
Group ii metabotropic glutamate receptor activity
Specific Function:
G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. May mediate suppression of neurotransmission or may be involved in synaptogenesis or synaptic stabilization.
Gene Name:
GRM2
Uniprot ID:
Q14416
Molecular Weight:
95566.715 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory35 uMNot AvailableBindingDB 50052553
References
  1. Brauner-Osborne H, Egebjerg J, Nielsen EO, Madsen U, Krogsgaard-Larsen P: Ligands for glutamate receptors: design and therapeutic prospects. J Med Chem. 2000 Jul 13;43(14):2609-45. [10893301 ]
General Function:
Group iii metabotropic glutamate receptor activity
Specific Function:
G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling inhibits adenylate cyclase activity.
Gene Name:
GRM4
Uniprot ID:
Q14833
Molecular Weight:
101866.835 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>3000 uMNot AvailableBindingDB 50052553
References
  1. Brauner-Osborne H, Egebjerg J, Nielsen EO, Madsen U, Krogsgaard-Larsen P: Ligands for glutamate receptors: design and therapeutic prospects. J Med Chem. 2000 Jul 13;43(14):2609-45. [10893301 ]
General Function:
Protein homodimerization activity
Specific Function:
G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity (By similarity). Signaling stimulates TRPM1 channel activity and Ca(2+) uptake. Required for normal vision.
Gene Name:
GRM6
Uniprot ID:
O15303
Molecular Weight:
95466.77 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory140 uMNot AvailableBindingDB 50052553
References
  1. Brauner-Osborne H, Egebjerg J, Nielsen EO, Madsen U, Krogsgaard-Larsen P: Ligands for glutamate receptors: design and therapeutic prospects. J Med Chem. 2000 Jul 13;43(14):2609-45. [10893301 ]