NP-MRD: Showing NP-Card for Aminoadipic acid (NP0000144)

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Record Information

Version

2.0

Created at

2005-11-16 15:48:42 UTC

Updated at

2020-11-24 22:13:11 UTC

NP-MRD ID

NP0000144

Secondary Accession Numbers

None

Natural Product Identification

Common Name

Aminoadipic acid

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 ).

Structure

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

     RDKit          2D

 22 21  0  0  0  0  0  0  0  0999 V2000
    2.0573    1.9939    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.3146    0.5162    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.8368    0.2588    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6409    0.0015    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1187   -0.2559    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5964   -0.5132    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.1124   -1.9217    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -4.5582    0.6379    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.5719   -0.9616    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5467   -2.0565    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.9804   -1.4776    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.7222    2.6778    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.2084    2.9557    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.7924    0.7735    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.4013    1.6942    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.9121   -1.2393    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8983    1.4792    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3836   -1.4763    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8613   -1.7336    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3760    1.2219    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   -6.0359    0.3805    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.2377   -2.9554    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  1  0
  4  5  1  0
  5  6  1  0
  6  7  2  0
  6  8  1  0
  2  9  1  0
  9 10  2  0
  9 11  1  0
  1 12  1  0
  1 13  1  0
  2 14  1  1
  3 15  1  1
  3 16  1  0
  4 17  1  6
  4 18  1  0
  5 19  1  6
  5 20  1  0
  8 21  1  0
 11 22  1  0
M  END
> <DATABASE_ID>
NP0000144

> <DATABASE_NAME>
NP-MRD

> <SMILES>
N[C@@H](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)/t4-/m0/s1

> <INCHI_KEY>
OYIFNHCXNCRBQI-BYPYZUCNSA-N

> <FORMULA>
C6H11NO4

> <MOLECULAR_WEIGHT>
161.1558

> <EXACT_MASS>
161.068807845

> <JCHEM_ACCEPTOR_COUNT>
5

> <JCHEM_ATOM_COUNT>
22

> <JCHEM_AVERAGE_POLARIZABILITY>
15.528857992657501

> <JCHEM_BIOAVAILABILITY>
1

> <JCHEM_DONOR_COUNT>
3

> <JCHEM_FORMAL_CHARGE>
0

> <JCHEM_GHOSE_FILTER>
0

> <JCHEM_IUPAC>
(2S)-2-aminohexanedioic acid

> <ALOGPS_LOGP>
-3.43

> <JCHEM_LOGP>
-2.799617140954382

> <ALOGPS_LOGS>
-0.69

> <JCHEM_MDDR_LIKE_RULE>
0

> <JCHEM_NUMBER_OF_RINGS>
0

> <JCHEM_PHYSIOLOGICAL_CHARGE>
-1

> <JCHEM_PKA>
4.417593887349678

> <JCHEM_PKA_STRONGEST_ACIDIC>
2.014430671538277

> <JCHEM_PKA_STRONGEST_BASIC>
9.52703004922271

> <JCHEM_POLAR_SURFACE_AREA>
100.62

> <JCHEM_REFRACTIVITY>
35.8887

> <JCHEM_ROTATABLE_BOND_COUNT>
5

> <JCHEM_RULE_OF_FIVE>
1

> <ALOGPS_SOLUBILITY>
3.27e+01 g/l

> <JCHEM_TRADITIONAL_IUPAC>
aminoadipate

> <JCHEM_VEBER_RULE>
0

$$$$

View in JSmol

Synonyms

Value	Source
(S)-2-Aminohexanedioic acid	ChEBI
L-2-Aminoadipate	ChEBI
L-2-Aminohexanedioate	ChEBI
L-alpha-Aminoadipate	ChEBI
L-alpha-Aminoadipic acid	ChEBI
L-2-Aminoadipic acid	Kegg
(S)-2-Aminohexanedioate	Generator
L-2-Aminohexanedioic acid	Generator
L-a-Aminoadipate	Generator
L-a-Aminoadipic acid	Generator
L-Α-aminoadipate	Generator
L-Α-aminoadipic acid	Generator
Aminoadipate	Generator
(2S)-2-Aminohexanedioic acid	HMDB
(2S)-2-Azaniumyl-6-hydroxy-6-oxohexanoate	HMDB
(S)-2-Aminoadipic acid	HMDB
2-Aminoadipate	HMDB
2-Aminoadipic acid	HMDB
2-Aminohexanedioic acid	HMDB
L-Aminoadipic acid	HMDB
alpha-Aminoadipic acid	HMDB
Α-aminoadipic acid	HMDB

Chemical Formula

C₆H₁₁NO₄

Average Mass

161.1558 Da

Monoisotopic Mass

161.06881 Da

IUPAC Name

(2S)-2-aminohexanedioic acid

Traditional Name

aminoadipate

CAS Registry Number

542-32-5

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 Key

OYIFNHCXNCRBQI-UHFFFAOYSA-N

Experimental Spectra

Spectrum Type	Description	Depositor Email	Depositor Organization	Depositor	Deposition Date	View
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, simulated)	Wishart Lab	Wishart Lab	David Wishart	2021-06-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, simulated)	Wishart Lab	Wishart Lab	David Wishart	2021-06-20	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, simulated)	Wishart Lab	Wishart Lab	David Wishart	2021-06-20	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, experimental)	Wishart Lab	Wishart Lab	David Wishart	2021-06-20	View Spectrum

Predicted Spectra

Not Available

Chemical Shift Submissions

Not Available

Species

Species of Origin

Species Name	Source	Reference
Arabidopsis thaliana	Plant	KNApSAcK
Caenorhabditis elegans	LOTUS Database	35616633
Cannabis sativa	CannabisDB	Not Available
Caylusea abyssinica	LOTUS Database	35616633
Cycas circinalis	LOTUS Database	35616633
Cycas revoluta	LOTUS Database	35616633
Flammulina velutipes	LOTUS Database	35616633
Homo sapiens	LOTUS Database	35616633
Lathyrus sativus	LOTUS Database	35616633
Phoma medicaginis	Fungi	KNApSAcK
Pisum sativum	LOTUS Database	35616633
Prunus domestica	LOTUS Database	35616633
Psophocarpus tetragonolobus	LOTUS Database	35616633
Streptomyces clavuligerus	LOTUS Database	35616633
Sus scrofa	LOTUS Database	35616633
Trypanosoma brucei	LOTUS Database	35616633
Vigna radiata	LOTUS Database	35616633

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.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

L-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 Framework

Aliphatic acyclic compounds

External Descriptors

2-aminoadipic acid (CHEBI:37023 )

Physical Properties

State

Solid

Experimental Properties

Property	Value	Reference
Melting Point	196 - 198 °C	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	2.2 mg/mL	Not Available
LogP	Not Available	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	32.7 g/L	ALOGPS
logP	-3.4	ALOGPS
logP	-2.8	ChemAxon
logS	-0.69	ALOGPS
pKa (Strongest Acidic)	2.01	ChemAxon
pKa (Strongest Basic)	9.53	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	100.62 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	35.89 m³·mol⁻¹	ChemAxon
Polarizability	15.53 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

HMDB0000510

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FoodDB ID

KNApSAcK ID

Chemspider ID

KEGG Compound ID

BioCyc ID

BiGG ID

Not Available

Wikipedia Link

Alpha-Aminoadipic_acid

METLIN ID

Not Available

PubChem Compound

92136

PDB ID

Not Available

ChEBI ID

37023

Good Scents ID

Not Available

References

General References

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 ]
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 ]
Hori S: [Pathophysiology of intraocular neovascularization]. Nippon Ganka Gakkai Zasshi. 1990 Dec;94(12):1103-21. [PubMed: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. [PubMed:9679552 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]

Showing NP-Card for Aminoadipic acid (NP0000144)

MOL for NP0000144 (Aminoadipic acid)

3D MOL for NP0000144 (Aminoadipic acid)

3D SDF for NP0000144 (Aminoadipic acid)

3D-SDF for NP0000144 (Aminoadipic acid)

PDB for NP0000144 (Aminoadipic acid)

3D PDB for NP0000144 (Aminoadipic acid)

SMILES for NP0000144 (Aminoadipic acid)

INCHI for NP0000144 (Aminoadipic acid)

Structure for NP0000144 (Aminoadipic acid)

3D Structure for NP0000144 (Aminoadipic acid)