T3DB: Oxoadipic acid

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (1)XML

Targets (1)

Record Information

Version

2.0

Creation Date

2014-08-29 06:08:00 UTC

Update Date

2018-03-21 17:46:12 UTC

Accession Number

T3D4257

Identification

Common Name

Oxoadipic acid

Class

Small Molecule

Description

2-Oxoadipic acid is produced from lysine in the cytosol of cells via the saccharopine and the pipecolic acid pathways. Catabolites of hydroxylysine and tryptophan enter these pathways as 2-aminoadipic-semialdehyde and 2-oxoadipate, respectively. In the mitochondrial matrix, 2-oxoadipate is decarboxylated to glutaryl-CoA by the 2-oxoadipate dehydrogenase complex and then converted into acetyl-CoA. Chronically high levels of oxoadipic acid are associated with at least two inborn errors of metabolism, including 2-aminoadipic aciduria and 2-oxoadipic aciduria. 2-Oxoadipic aciduria is an inborn error of metabolism involving lysine, tryptophan, and hydroxylysine, in which abnormal quantities of 2-aminoadipic acid are found in body fluids along with 2-oxoadipic acid. Patients with 2-oxoadipic acidemias are mentally retarded with hypotonia or seizures. 2-Oxoadipic aciduria can occur in patients with Kearns-Sayre syndrome, a progressive disorder with onset prior to 20 years of age in which multiple organ systems are affected. Affected individuals have progressive external ophthalmoplegia (PEO) and retinopathy, both of which are classically associated with abnormalities in cardiac conduction, cerebellar signs, and elevated cerebrospinal fluid protein (PMID: 10655159, 16183823, 11083877). When present in sufficiently high levels, oxoadipic acid can act as an acidogen and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Oxoadipic acid is an organic acid. 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.

Compound Type

Animal Toxin
Food Toxin
Metabolite
Natural Compound
Organic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
2-Keto-adipate
2-Ketoadipate
2-Ketoadipic acid
2-Oxo-hexanedioate
2-Oxo-hexanedioic acid
2-Oxoadipate
2-Oxoadipic acid
2-Oxohexanedioate
2-Oxohexanedioic acid
2-Oxohexanedionic acid
a-Ketoadipate
a-Ketoadipic acid
a-Oxoadipate
a-Oxoadipic acid
alpha-Ketoadipate
alpha-Ketoadipic acid
alpha-Oxoadipate
alpha-Oxoadipic acid
Oxoadipate

Chemical Formula

C₆H₈O₅

Average Molecular Mass

160.125 g/mol

Monoisotopic Mass

160.037 g/mol

CAS Registry Number

3184-35-8

IUPAC Name

2-oxohexanedioic acid

Traditional Name

oxoadipate

SMILES

OC(=O)CCCC(=O)C(O)=O

InChI Identifier

InChI=1S/C6H8O5/c7-4(6(10)11)2-1-3-5(8)9/h1-3H2,(H,8,9)(H,10,11)

InChI Key

InChIKey=FGSBNBBHOZHUBO-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as medium-chain keto acids and derivatives. These are keto acids with a 6 to 12 carbon atoms long side chain.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Keto acids and derivatives

Sub Class

Medium-chain keto acids and derivatives

Direct Parent

Medium-chain keto acids and derivatives

Alternative Parents

Substituents

Medium-chain keto acid
Dicarboxylic acid or derivatives
Alpha-keto acid
Alpha-hydroxy ketone
Ketone
Carboxylic acid
Carboxylic acid derivative
Organic oxygen compound
Organic oxide
Hydrocarbon derivative
Organooxygen compound
Carbonyl group
Aliphatic acyclic compound

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

oxo dicarboxylic acid (CHEBI:15753 )
Dicarboxylic acids (LMFA01170121 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular
Mitochondria

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Name	SMPDB Link	KEGG Link
Lysine Degradation	SMP00037	map00310
2-aminoadipic 2-oxoadipic aciduria	SMP00719	Not Available

Applications

Not Available

Biological Roles

human metabolite

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	127°C
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	23.4 g/L	ALOGPS
logP	-0.37	ALOGPS
logP	0.34	ChemAxon
logS	-0.83	ALOGPS
pKa (Strongest Acidic)	2.84	ChemAxon
pKa (Strongest Basic)	-9.7	ChemAxon
Physiological Charge	-2	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	91.67 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	33.48 m³·mol⁻¹	ChemAxon
Polarizability	14.16 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-002b-3910000000-66f39a8b247786a425e6	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-002k-3910000000-977efef811bb47535b80	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0udr-6900000000-0eb27647b831277a2aef	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0udr-6900000000-46cd4d782e3d19030993	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-002b-3910000000-66f39a8b247786a425e6	2018-05-18	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-002k-3910000000-977efef811bb47535b80	2018-05-18	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0udr-6900000000-0eb27647b831277a2aef	2018-05-18	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0udr-6900000000-46cd4d782e3d19030993	2018-05-18	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-00r6-9300000000-b3f156c173adabf3f1bb	2016-09-22	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positive	splash10-0079-9830000000-a3b1d5e6d378582a6fc2	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0a4i-0900000000-aef94cc19e461712a097	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0bt9-9500000000-9326906313591bb9da1c	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0a4i-9000000000-05db676896bb1e350497	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0a4l-9000000000-1e566f572b14692461f2	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , negative	splash10-0006-9000000000-527da1c1c271db4d8db4	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , negative	splash10-0a4i-9600000000-38ade0e080ecb7a89588	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Negative	splash10-0a4i-9000000000-ea231700b469554fcdb4	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-9300000000-d69c9552085fc7db91fc	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Negative	splash10-052f-9000000000-fa207039b6913600e1b4	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9000000000-dc580b3d8a9e58ea79c6	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-9200000000-f25470d83f4df952958e	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Negative	splash10-0a4i-9000000000-c524dfcde428d896e041	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9000000000-3e6aec4efdb02abcf887	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0006-2900000000-757eb57780db9df4f78d	2015-09-15	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-016v-9700000000-675e5732632f0a0cabe1	2015-09-15	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9000000000-1da8154067fdb9a27459	2015-09-15	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-1900000000-0e26a52af95eb287809d	2015-09-15	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-066v-7900000000-d898e0593464c13b3f89	2015-09-15	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-052g-9100000000-34782bad1c8755ac897d	2015-09-15	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-014v-9800000000-1b44ce4709a42734f384	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00kf-9000000000-e16740a0d326b489193c	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9000000000-99207abec9ffe380ff34	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0295-5900000000-d4320b8980ff5d5a03d3	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-00kb-9100000000-27e2c4cbbb4945978dc1	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9000000000-bc42e02ad867f6ce85a4	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, DMSO-d6, experimental)	Not Available	2014-09-20	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 22.53 MHz, DMSO-d6, experimental)	Not Available	2014-09-23	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 500 MHz, H₂O, experimental)	Not Available	2012-12-05	View Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

In the matrix of mitochondria, 2-oxoadipate is decarboxylated to glutaryl-CoA by the 2-oxoadipate dehydrogenase complex and then converted to acetyl-CoA. Accumulation of oxoadipic acid in the body has been shown to be toxic.

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

This is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.

Minimum Risk Level

Not Available

Health Effects

Chronically high levels of oxoadipic acid are associated with at least 2 inborn errors of metabolism including: 2-aminoadipic and 2-oxoadipic aciduria.

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

HMDB00225

PubChem Compound ID

ChEMBL ID

Not Available

ChemSpider ID

KEGG ID

C00322

UniProt ID

Not Available

OMIM ID

ChEBI ID

15753

BioCyc ID

2K-ADIPATE

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Not Available

References

Synthesis Reference

Nelson, Randall B.; Gribble, Gordon W. Preparation of a-ketoadipic acid. Organic Preparations and Procedures International (1973), 5(2), 55-8.

MSDS

Link

General References

Barshop BA, Nyhan WL, Naviaux RK, McGowan KA, Friedlander M, Haas RH: Kearns-Sayre syndrome presenting as 2-oxoadipic aciduria. Mol Genet Metab. 2000 Jan;69(1):64-8. [10655159 ]
Schulze-Bergkamen A, Okun JG, Spiekerkotter U, Lindner M, Haas D, Kohlmuller D, Mayatepek E, Schulze-Bergkamen H, Greenberg CR, Zschocke J, Hoffmann GF, Kolker S: Quantitative acylcarnitine profiling in peripheral blood mononuclear cells using in vitro loading with palmitic and 2-oxoadipic acids: biochemical confirmation of fatty acid oxidation and organic acid disorders. Pediatr Res. 2005 Nov;58(5):873-80. Epub 2005 Sep 23. [16183823 ]
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 ]
Guneral F, Bachmann C: Age-related reference values for urinary organic acids in a healthy Turkish pediatric population. Clin Chem. 1994 Jun;40(6):862-6. [8087979 ]
Lee SH, Kim SO, Chung BC: Gas chromatographic-mass spectrometric determination of urinary oxoacids using O-(2,3,4,5,6-pentafluorobenzyl)oxime-trimethylsilyl ester derivatization and cation-exchange chromatography. J Chromatogr B Biomed Sci Appl. 1998 Nov 20;719(1-2):1-7. [9869358 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Glutaryl-CoA dehydrogenase, mitochondrial

General Function:: Oxidoreductase activity, acting on the ch-ch group of donors, with a flavin as acceptor
Specific Function:: Catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA and CO(2) in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism. It uses electron transfer flavoprotein as its electron acceptor. Isoform Short is inactive.
Gene Name:: GCDH
Uniprot ID:: Q92947
Molecular Weight:: 48126.715 Da

Oxoadipic acid (T3D4257)

Structure for T3D4257: Oxoadipic acid

Targets