T3DB: Glutaconic 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 06:33:58 UTC

Update Date

2018-03-21 17:46:19 UTC

Accession Number

T3D4358

Identification

Common Name

Glutaconic acid

Class

Small Molecule

Description

Glutaconic acid is related to the fully saturated glutaric acid and belongs to the class of compounds known as dicarboxylic acids and derivatives. These are organic compounds containing exactly two carboxylic acid groups. Glutaconic acid is soluble (in water) and a weakly acidic compound (based on its pKa). Glutaconic acid has been detected in the urine of individuals with inborn errors of metabolism. When present in sufficiently high levels, glutaconic acid can act as an acidogen, a neurotoxin, and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A neurotoxin is a compound that is toxic to neural tissues and cells. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of glutaconic acid are associated with glutaric aciduria type I (glutaric acidemia type I, glutaryl-CoA dehydrogenase deficiency, GA1, or GAT1). GA1 is an inherited disorder in which the body is unable to completely break down the amino acids lysine, hydroxylysine and tryptophan. Excessive levels of their intermediate breakdown products (e.g. glutaric acid, glutaryl-CoA, 3-hydroxyglutaric acid, glutaconic acid) can accumulate and cause damage to the brain (and also other organs). Babies with glutaric acidemia type I are often born with unusually large heads (macrocephaly). Macrocephaly is amongst the earliest signs of GA1. GA1 also causes secondary carnitine deficiency because glutaconic acid, like other organic acids, is detoxified by carnitine. 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, liver, and kidney abnormalities, seizures, coma, and possibly death. These are also the characteristic symptoms of untreated glutaric aciduria. 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. Glutaconic acid's neurotoxicity is thought to be partially caused by an excitotoxic mechanism in which glutaconic acid overactivates N-methyl-D-aspartate (NMDA) receptors. Accumulating trans-glutaconic (TG) acids have been proposed to be involved in the development of the striatal degeneration seen in children with glutaric acidemia type I via an excitotoxic mechanism.

Compound Type

Animal Toxin
Ester
Food Toxin
Metabolite
Natural Compound
Organic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(E)-2-Pentenedioate
(E)-2-Pentenedioic acid
(E)-Glutaconate
(E)-Glutaconic acid
1,3-Propenedicarboxylate
1,3-Propenedicarboxylic acid
1-Propene-1,3-dicarboxylate
1-Propene-1,3-dicarboxylic acid
Glutaconate
Pentenedioate
Pentenedioic acid
trans-Glutaconate
trans-Glutaconic acid

Chemical Formula

C₅H₆O₄

Average Molecular Mass

130.099 g/mol

Monoisotopic Mass

130.027 g/mol

CAS Registry Number

1724-02-3

IUPAC Name

(2E)-pent-2-enedioic acid

Traditional Name

glutaconic acid

SMILES

[H]\C(CC(O)=O)=C(\[H])C(O)=O

InChI Identifier

InChI=1S/C5H6O4/c6-4(7)2-1-3-5(8)9/h1-2H,3H2,(H,6,7)(H,8,9)/b2-1+

InChI Key

InChIKey=XVOUMQNXTGKGMA-OWOJBTEDSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as dicarboxylic acids and derivatives. These are organic compounds containing exactly two carboxylic acid groups.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Dicarboxylic acids and derivatives

Direct Parent

Dicarboxylic acids and derivatives

Alternative Parents

Substituents

Fatty acyl
Fatty acid
Unsaturated fatty acid
Dicarboxylic acid or derivatives
Carboxylic acid
Organic oxygen compound
Organic oxide
Hydrocarbon derivative
Organooxygen compound
Carbonyl group
Aliphatic acyclic compound

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

glutaconic acid (CHEBI:15670 )
Dicarboxylic acids (LMFA01170109 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Name	SMPDB Link	KEGG Link
Glutaric Aciduria Type I	SMP00185	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	133 - 135°C
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	17.6 g/L	ALOGPS
logP	0.05	ALOGPS
logP	0.044	ChemAxon
logS	-0.87	ALOGPS
pKa (Strongest Acidic)	3.69	ChemAxon
Physiological Charge	-2	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	74.6 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	29.23 m³·mol⁻¹	ChemAxon
Polarizability	11.36 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)	splash10-0002-3930000000-d1b6e04bed9f3de84afa	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0002-3910000000-02c8fdec1f78bd5117e2	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0002-3930000000-d1b6e04bed9f3de84afa	2018-05-18	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0002-3910000000-02c8fdec1f78bd5117e2	2018-05-18	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0002-3930000000-d1b6e04bed9f3de84afa	2018-05-18	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0002-3910000000-02c8fdec1f78bd5117e2	2018-05-18	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0002-3930000000-d1b6e04bed9f3de84afa	2018-05-18	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-0002-3910000000-02c8fdec1f78bd5117e2	2018-05-18	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-001r-9100000000-42f59aea4f8e6bb8ab57	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positive	splash10-05g0-8920000000-733f5a9f839df29bff69	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 (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 (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_2_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Negative (Annotated)	splash10-000i-9000000000-6fb6cc9ab31410b273f1	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Negative (Annotated)	splash10-000f-9000000000-b9c27f4002ce9f12f916	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Negative (Annotated)	splash10-000f-9100000000-d627e3ddfe858b1b331d	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 7V, positive	splash10-000i-9100000000-ab58b5793b44b9bf9179	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 10V, positive	splash10-00ds-9100000000-d837a612ccd5753681fe	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 15V, positive	splash10-00ds-9000000000-297bd6690b68056be798	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - QTOF 17V, positive	splash10-006t-9000000000-fcf4434d16f307cff090	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 0V, positive	splash10-03di-2900000000-2e649f3de9cd6e527eb8	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 0V, positive	splash10-03di-4900000000-49e2416d6fb162ad2653	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 0V, positive	splash10-03dr-6900000000-de40796dc1578c547169	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 0V, positive	splash10-01p9-9700000000-5d5dcebba638d34e8fac	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 1V, positive	splash10-01p9-9400000000-eb38aa127f9847501c88	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 1V, positive	splash10-000i-9300000000-cd256964e84b2c9e7330	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 1V, positive	splash10-000i-9100000000-ec0b1e5f63f16ae5f6ba	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 1V, positive	splash10-000i-9100000000-225d56adbb31a91aea12	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 2V, positive	splash10-000i-9100000000-f7162d7b901bcae643ba	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 2V, positive	splash10-000i-9000000000-fa9f8d6b587fca352dd5	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 2V, positive	splash10-000i-9000000000-77c952cabb0213b55f1e	2020-07-22	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 3V, positive	splash10-0079-9000000000-e0422714c30ca69f9b7e	2020-07-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-03e9-3900000000-f982ee0bd6ebcaf33bbe	2017-09-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-01q0-9500000000-90dd8c522781e5da5ebb	2017-09-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00n0-9000000000-e56400244a361d348a1f	2017-09-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-004i-1900000000-ad86855e24f296413178	2017-09-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-01t9-4900000000-30e4a1adead132f7de92	2017-09-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-052f-9000000000-47a3aa8cf8913cc4d70e	2017-09-01	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, 100 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, H₂O, experimental)	Not Available	2012-12-05	View Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

Accumulating trans-glutaconic (TG) acids has been proposed to be involved in the development of the striatal degeneration seen in children with glutaric acidemia type 1 (GA1) via an excitotoxic mechanism. TG is neurotoxic and neurotoxicity is thought to be caused by an excitotoxic mechanism in which TG overactivates N-methyl-D-aspartate (NMDA) receptors. (3) In glutaric aciduria type 1, glutaconic acid accumulates, resulting in brain damage. (Wikipedia)

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 glutaconic acid are associated with Glutaric Aciduria Type I.

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

15670

BioCyc ID

GLUTACONATE

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Glutaconic acid

References

Synthesis Reference

Schwarz, Siegfried; Bohn, Helmut; Schmidt, Dieter; Kulpa, Manfred; Spakowski, Horst; Becker, Manfred. Glutaconic acid. Ger. (East) (1967), 2 pp.

MSDS

Link

General References

Podebrad F, Heil M, Beck T, Mosandl A, Sewell AC, Bohles H: Stereodifferentiation of 3-hydroxyisobutyric- and 3-aminoisobutyric acid in human urine by enantioselective multidimensional capillary gas chromatography-mass spectrometry. Clin Chim Acta. 2000 Feb 25;292(1-2):93-105. [10686279 ]
Osaka H, Kimura S, Nezu A, Yamazaki S, Saitoh K, Yamaguchi S: Chronic subdural hematoma, as an initial manifestation of glutaric aciduria type-1. Brain Dev. 1993 Mar-Apr;15(2):125-7. [8214331 ]
Lund TM, Christensen E, Kristensen AS, Schousboe A, Lund AM: On the neurotoxicity of glutaric, 3-hydroxyglutaric, and trans-glutaconic acids in glutaric acidemia type 1. J Neurosci Res. 2004 Jul 1;77(1):143-7. [15197747 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

1. NMDA receptor (Protein Group)

General Function:: Voltage-gated cation channel activity
Specific Function:: NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. Is involved in the cell surface targeting of NMDA receptors (By similarity).
Included Proteins:: Q05586 , Q12879 , Q13224 , Q14957 , O15399 , Q8TCU5 , O60391

Glutaconic acid (T3D4358)

Structure for T3D4358: Glutaconic acid

Targets