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Record Information
Version1.0
Created at2005-11-16 15:48:42 UTC
Updated at2020-11-24 22:13:11 UTC
NP-MRD IDNP0000144
Secondary Accession NumbersNone
Natural Product Identification
Common NameAminoadipic acid
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 ).
Structure
Thumb
Synonyms
ValueSource
(S)-2-Aminohexanedioic acidChEBI
L-2-AminoadipateChEBI
L-2-AminohexanedioateChEBI
L-alpha-AminoadipateChEBI
L-alpha-Aminoadipic acidChEBI
L-2-Aminoadipic acidKegg
(S)-2-AminohexanedioateGenerator
L-2-Aminohexanedioic acidGenerator
L-a-AminoadipateGenerator
L-a-Aminoadipic acidGenerator
L-Α-aminoadipateGenerator
L-Α-aminoadipic acidGenerator
AminoadipateGenerator
(2S)-2-Aminohexanedioic acidHMDB
(2S)-2-Azaniumyl-6-hydroxy-6-oxohexanoateHMDB
(S)-2-Aminoadipic acidHMDB
2-AminoadipateHMDB
2-Aminoadipic acidHMDB
2-Aminohexanedioic acidHMDB
L-Aminoadipic acidHMDB
alpha-Aminoadipic acidHMDB
Α-aminoadipic acidHMDB
Chemical FormulaC6H11NO4
Average Mass161.1558 Da
Monoisotopic Mass161.06881 Da
IUPAC Name(2S)-2-aminohexanedioic acid
Traditional Nameaminoadipate
CAS Registry Number542-32-5
SMILES
NC(CCCC(O)=O)C(O)=O
InChI Identifier
InChI=1S/C6H11NO4/c7-4(6(10)11)2-1-3-5(8)9/h4H,1-3,7H2,(H,8,9)(H,10,11)
InChI KeyOYIFNHCXNCRBQI-UHFFFAOYSA-N
Spectra
Spectrum TypeDescriptionDepositor IDDeposition DateView
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, simulated)Wishart Lab2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, simulated)Wishart Lab2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, simulated)Wishart Lab2021-06-20View Spectrum
2D NMR[1H, 13C] NMR Spectrum (2D, 500 MHz, D2O, experimental)Wishart Lab2021-06-20View Spectrum
2D NMR[1H, 13C] NMR Spectrum (2D, 500 MHz, D2O, experimental)Wishart Lab2021-06-20View Spectrum
Species
Species of Origin
  • Animalia
  • Plantae
  • Chemical Taxonomy
    Description Belongs to the class of organic compounds known as l-alpha-amino acids. These are alpha amino acids which have the L-configuration of the alpha-carbon atom.
    KingdomOrganic compounds
    Super ClassOrganic acids and derivatives
    ClassCarboxylic acids and derivatives
    Sub ClassAmino acids, peptides, and analogues
    Direct ParentL-alpha-amino acids
    Alternative Parents
    Substituents
    • L-alpha-amino acid
    • Medium-chain fatty acid
    • Amino fatty acid
    • Dicarboxylic acid or derivatives
    • Fatty acid
    • Fatty acyl
    • Amino acid
    • Carboxylic acid
    • Organopnictogen compound
    • Organic nitrogen compound
    • Amine
    • Organic oxygen compound
    • Primary amine
    • Organooxygen compound
    • Organonitrogen compound
    • Primary aliphatic amine
    • Carbonyl group
    • Hydrocarbon derivative
    • Organic oxide
    • Aliphatic acyclic compound
    Molecular FrameworkAliphatic acyclic compounds
    External Descriptors
    Physical Properties
    StateSolid
    Experimental Properties
    PropertyValueReference
    Melting Point196 - 198 °CNot Available
    Boiling PointNot AvailableNot Available
    Water Solubility2.2 mg/mLNot Available
    LogPNot AvailableNot 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
    BioavailabilityYesChemAxon
    Rule of FiveYesChemAxon
    Ghose FilterNoChemAxon
    Veber's RuleNoChemAxon
    MDDR-like RuleNoChemAxon
    External Links
    HMDB IDHMDB0000510
    DrugBank IDNot Available
    Phenol Explorer Compound IDNot Available
    FoodDB IDFDB021812
    KNApSAcK IDC00007393
    Chemspider ID83182
    KEGG Compound IDC00956
    BioCyc IDCPD-468
    BiGG IDNot Available
    Wikipedia LinkAlpha-Aminoadipic_acid
    METLIN IDNot Available
    PubChem Compound92136
    PDB IDNot Available
    ChEBI ID37023
    Good Scents IDNot Available
    References
    General References
    1. 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. [PubMed:11083877 ]
    2. 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. [PubMed:19212411 ]
    3. 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. [PubMed:8759641 ]
    4. Hori S: [Pathophysiology of intraocular neovascularization]. Nippon Ganka Gakkai Zasshi. 1990 Dec;94(12):1103-21. [PubMed:1707214 ]
    5. 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. [PubMed:9679552 ]
    6. Mechanic GL: The qualitative and quantitative crosslink chemistry of collagen matrices. Adv Exp Med Biol. 1977;86B:699-708. [PubMed:20755 ]
    7. 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. [PubMed:8087205 ]
    8. 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. [PubMed:8487492 ]
    9. 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. [PubMed:8566117 ]
    10. 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. [PubMed:23737455 ]
    11. 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. [PubMed:23141293 ]
    12. 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. [PubMed:17313367 ]
    13. 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. [PubMed:15389298 ]
    14. 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. [PubMed:21961526 ]
    15. 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. [PubMed:21647514 ]
    16. 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. [PubMed:18448817 ]
    17. Wang TJ, Ngo D, Psychogios N, Dejam A, Larson MG, Vasan RS, Ghorbani A, O'Sullivan J, Cheng S, Rhee EP, Sinha S, McCabe E, Fox CS, O'Donnell CJ, Ho JE, Florez JC, Magnusson M, Pierce KA, Souza AL, Yu Y, Carter C, Light PE, Melander O, Clish CB, Gerszten RE: 2-Aminoadipic acid is a biomarker for diabetes risk. J Clin Invest. 2013 Oct;123(10):4309-17. doi: 10.1172/JCI64801. Epub 2013 Sep 16. [PubMed:24091325 ]
    18. Lin H, Levison BS, Buffa JA, Huang Y, Fu X, Wang Z, Gogonea V, DiDonato JA, Hazen SL: Myeloperoxidase-mediated protein lysine oxidation generates 2-aminoadipic acid and lysine nitrile in vivo. Free Radic Biol Med. 2017 Mar;104:20-31. doi: 10.1016/j.freeradbiomed.2017.01.006. Epub 2017 Jan 6. [PubMed:28069522 ]