| Record Information |
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| Version | 2.0 |
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| Creation Date | 2014-08-29 06:08:19 UTC |
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| Update Date | 2018-03-21 17:46:12 UTC |
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| Accession Number | T3D4259 |
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| Identification |
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| Common Name | Aminoadipic acid |
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| Class | Small Molecule |
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| Description | Aminoadipic 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). |
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| Compound Type | - Amine
- Animal Toxin
- Food Toxin
- Industrial/Workplace Toxin
- Metabolite
- Natural Compound
- Organic Compound
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| Chemical Structure | |
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| 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 |
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| Chemical Formula | C6H11NO4 |
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| Average Molecular Mass | 161.156 g/mol |
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| Monoisotopic Mass | 161.069 g/mol |
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| CAS Registry Number | 542-32-5 |
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| IUPAC Name | 2-aminohexanedioic acid |
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| Traditional Name | aminoadipic acid |
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| SMILES | NC(CCCC(O)=O)C(O)=O |
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| InChI Identifier | InChI=1/C6H11NO4/c7-4(6(10)11)2-1-3-5(8)9/h4H,1-3,7H2,(H,8,9)(H,10,11) |
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| InChI Key | InChIKey=OYIFNHCXNCRBQI-UHFFFAOYNA-N |
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| Chemical Taxonomy |
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| 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). |
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| Kingdom | Organic compounds |
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| Super Class | Organic acids and derivatives |
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| Class | Carboxylic acids and derivatives |
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| Sub Class | Amino acids, peptides, and analogues |
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| Direct Parent | Alpha amino acids |
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| Alternative Parents | |
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| 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
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| Molecular Framework | Aliphatic acyclic compounds |
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| External Descriptors | |
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| Biological Properties |
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| Status | Detected and Not Quantified |
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| Origin | Endogenous |
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| Cellular Locations | - Cytoplasm
- Membrane
- Mitochondria
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| Biofluid Locations | Not Available |
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| Tissue Locations | |
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| Pathways | |
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| Applications | Not Available |
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| Biological Roles | |
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| Chemical Roles | Not Available |
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| Physical Properties |
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| State | Solid |
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| Appearance | White powder. |
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| Experimental Properties | | Property | Value |
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| Melting Point | 196 - 198°C | | Boiling Point | Not Available | | Solubility | 2.2 mg/mL | | LogP | Not Available |
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| Predicted Properties | |
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| Spectra |
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| Spectra | | Spectrum Type | Description | Splash Key | Deposition Date | View |
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| GC-MS | GC-MS Spectrum - GC-EI-TOF (Non-derivatized) | splash10-02di-0950000000-ec4fd991a53a8b6bc6ae | 2017-09-12 | View Spectrum | | GC-MS | GC-MS Spectrum - GC-EI-TOF (Non-derivatized) | splash10-02di-0950000000-ec4fd991a53a8b6bc6ae | 2018-05-18 | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | splash10-00r6-9300000000-9ef33042820e032c1af3 | 2017-09-01 | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positive | splash10-00ri-9620000000-052fe671da5a64787657 | 2017-10-06 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated) | splash10-03xv-2900000000-58b4f0b3e06cbb7abb90 | 2012-07-24 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated) | splash10-0a4j-9000000000-cc9c0c03f7c3890b531c | 2012-07-24 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated) | splash10-0a4i-9000000000-7b74167f01c922da9ef7 | 2012-07-24 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-ITFT , positive | splash10-0002-9400000000-71832a0d1e49341749a7 | 2017-09-14 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - QqQ 20V, negative | splash10-014l-2900000000-08df6df87d0bea6dce31 | 2020-07-21 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - n/a 11V, negative | splash10-0006-0900000000-99e7d8729f7099c6e9ea | 2020-07-21 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - Orbitrap 2V, negative | splash10-03di-0900000000-f542aa2756da9aa3ecb6 | 2020-07-22 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - Orbitrap 2V, negative | splash10-03di-0900000000-3133117467ce925161cb | 2020-07-22 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - Orbitrap 3V, negative | splash10-03di-0900000000-9e5f27d91fd799c059d6 | 2020-07-22 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - Orbitrap 4V, negative | splash10-03xu-0900000000-b801b3a34049e54a2915 | 2020-07-22 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - Orbitrap 5V, negative | splash10-014i-1900000000-2ef33d8640c4e5788618 | 2020-07-22 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - Orbitrap 6V, negative | splash10-014i-1900000000-281e4277990becc84832 | 2020-07-22 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - Orbitrap 8V, negative | splash10-014i-2900000000-a56c711aeb57c767fed8 | 2020-07-22 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - n/a 11V, negative | splash10-0006-0900000000-862ae5fa10820c14bdf1 | 2020-07-22 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - n/a 11V, negative | splash10-006t-9400000000-e007d0e2c3cec7f1a02c | 2020-07-22 | View Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - n/a 11V, negative | splash10-0002-9000000000-4755db14192225e1eebf | 2020-07-22 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-00kg-2900000000-3e45ac769d3b229221a3 | 2015-04-24 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-01ba-9600000000-c51318834cc371625d46 | 2015-04-24 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-05fu-9000000000-edbc970f12ea186bcf06 | 2015-04-24 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-03di-1900000000-0f7002659f604cc69395 | 2015-04-25 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-01ox-4900000000-bf42ddc971a2a05516a2 | 2015-04-25 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-0abc-9100000000-1979c27463bab7d33d58 | 2015-04-25 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-014i-4900000000-7913a597d0c94eebe02d | 2021-10-21 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-00dj-9100000000-523aa25ee55f888299e1 | 2021-10-21 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-0a4i-9000000000-0dcf3a7ca5d4e20885ee | 2021-10-21 | View Spectrum | | 1D NMR | 1H NMR Spectrum (1D, 600 MHz, H2O, experimental) | Not Available | 2012-12-04 | View Spectrum | | 1D NMR | 1H NMR Spectrum (1D, D2O, experimental) | Not Available | 2016-10-22 | View Spectrum | | 1D NMR | 13C NMR Spectrum (1D, D2O, experimental) | Not Available | 2016-10-22 | View Spectrum | | 2D NMR | [1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental) | Not Available | 2012-12-05 | View Spectrum |
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| Toxicity Profile |
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| Route of Exposure | Not Available |
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| Mechanism of Toxicity | Not Available |
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| Metabolism | Not Available |
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| Toxicity Values | Not Available |
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| Lethal Dose | Not Available |
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| Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). |
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| Uses/Sources | This is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation. |
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| Minimum Risk Level | Not Available |
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| Health Effects | Chronically high levels of aminoadipic acid are associated with at least 2 inborn errors of metabolism including: : 2-aminoadipic and 2-oxoadipic aciduria. |
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| Symptoms | Not Available |
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| Treatment | Not Available |
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| Normal Concentrations |
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| Not Available |
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| Abnormal Concentrations |
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| Not Available |
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| External Links |
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| DrugBank ID | Not Available |
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| HMDB ID | HMDB00510 |
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| PubChem Compound ID | 469 |
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| ChEMBL ID | CHEMBL433238 |
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| ChemSpider ID | 456 |
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| KEGG ID | C00956 |
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| UniProt ID | Not Available |
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| OMIM ID | |
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| ChEBI ID | 37024 |
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| BioCyc ID | CPD-468 |
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| CTD ID | Not Available |
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| Stitch ID | Not Available |
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| PDB ID | Not Available |
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| ACToR ID | Not Available |
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| Wikipedia Link | alpha-Aminoadipate |
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| References |
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| Synthesis Reference | Khan, Naseem H.; Ali, Mohd.; Panda, H.; Rakhshinda. Synthesis of a-aminoadipic acid. Journal of the Indian Chemical Society (1982), 59(9), 1077-8. |
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| MSDS | Link |
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| General References | - 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- Hori S: [Pathophysiology of intraocular neovascularization]. Nihon Ganka Gakkai Zasshi. 1990 Dec;94(12):1103-21. [1707214 ]
- 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 ]
- Mechanic GL: The qualitative and quantitative crosslink chemistry of collagen matrices. Adv Exp Med Biol. 1977;86B:699-708. [20755 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
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| Gene Regulation |
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| Up-Regulated Genes | Not Available |
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| Down-Regulated Genes | Not Available |
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