Glutaric acid (T3D4359)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (1)XML
Targets (1)
Record Information
Version2.0
Creation Date2014-08-29 06:34:02 UTC
Update Date2018-03-21 17:46:18 UTC
Accession NumberT3D4359
Identification
Common NameGlutaric acid
ClassSmall Molecule
DescriptionGlutaric acid is a simple five-carbon linear dicarboxylic acid. Glutaric acid is naturally produced in the body during the metabolism of some amino acids, including lysine and tryptophan. Glutaric acid may cause irritation to the skin and eyes. When present in sufficiently high levels, glutaric 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. Chronically high levels of glutaric acid are associated with at least three inborn errors of metabolism, including glutaric aciduria type I, malonyl-CoA decarboxylase deficiency, and glutaric aciduria type III. Glutaric aciduria type I (glutaric acidemia type I, glutaryl-CoA dehydrogenase deficiency, GA1, or GAT1) is an inherited disorder in which the body is unable to completely break down the amino acids lysine, hydroxylysine, and tryptophan due to a deficiency of mitochondrial glutaryl-CoA dehydrogenase (EC 1.3.99.7, GCDH). 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 glutaric 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. Treatment of glutaric aciduria is mainly based on the restriction of lysine intake, supplementation of carnitine, and an intensification of therapy during intercurrent illnesses. The major principle of dietary treatment is to reduce the production of glutaric acid and 3-hydroxyglutaric acid by restriction of natural protein, in general, and of lysine, in particular (PMID: 17465389, 15505398).
Compound Type
  • Animal Toxin
  • Food Toxin
  • Industrial/Workplace Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
1,3-Propanedicarboxylate
1,3-Propanedicarboxylic acid
1,5-Pentanedioate
1,5-Pentanedioic acid
Glutarate
Pentandioate
Pentandioic acid
Pentanedioate
Pentanedioic acid
Chemical FormulaC5H8O4
Average Molecular Mass132.115 g/mol
Monoisotopic Mass132.042 g/mol
CAS Registry Number110-94-1
IUPAC Namepentanedioic acid
Traditional Nameglutaric acid
SMILESOC(=O)CCCC(O)=O
InChI IdentifierInChI=1S/C5H8O4/c6-4(7)2-1-3-5(8)9/h1-3H2,(H,6,7)(H,8,9)
InChI KeyInChIKey=JFCQEDHGNNZCLN-UHFFFAOYSA-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.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassDicarboxylic acids and derivatives
Direct ParentDicarboxylic acids and derivatives
Alternative Parents
Substituents
  • Fatty acid
  • Dicarboxylic acid or derivatives
  • Carboxylic acid
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Glutaric Aciduria Type ISMP00185 Not Available
Glutaric Aciduria Type IIISMP00186 Not Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point95.8°C
Boiling Point200°C (392°F)
Solubility1600.0 mg/mL
LogP-0.29
Predicted Properties
PropertyValueSource
logP0.046ChemAxon
pKa (Strongest Acidic)3.76ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.6 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity28.14 m³·mol⁻¹ChemAxon
Polarizability12.17 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)splash10-0f6t-2940000000-9f099473c4a6eb94d4be2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)splash10-0002-1920000000-4ade63738a1c00460a632014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-0002-1910000000-743df9571fee7baa34172014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)splash10-00fs-9710000000-ba958e52b1424e5d48402014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-0cgj-3930000000-298fe512c6b58220ee332014-06-16View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-052o-9000000000-663deab1ce6413c4859d2017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0002-0920000000-56bce366cac24cd6773f2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0f6t-2940000000-9f099473c4a6eb94d4be2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0002-1920000000-4ade63738a1c00460a632017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0002-1910000000-743df9571fee7baa34172017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00fs-9710000000-ba958e52b1424e5d48402017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0cgj-3930000000-298fe512c6b58220ee332017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0002-0910000000-86fbcf8f1c72fbb2ffd02017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-01q3-9200000000-fcbc36fd55a7945d3f252017-08-28View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-05g3-9610000000-07394eb05b518a4e3bf42017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, N/A (Annotated)splash10-0019-9500000000-9db56ca3a541f0ce07d12012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, N/A (Annotated)splash10-052r-9100000000-991f69d0892976558f852012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, N/A (Annotated)splash10-0536-9300000000-20fb2c8dd136e4924aca2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-001i-0900000000-8eb90c15915f014713ac2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-000i-9200000000-2ffdc08c49952e135a862012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-000i-9000000000-8884b857c9582288f35a2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-052f-9000000000-7d2c0333bdce4dbabbc62012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-0006-9000000000-9ab2a9480833026416282012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-000i-9400000000-c5ec3115706f6041b8682012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-001i-0900000000-8eb90c15915f014713ac2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-000i-9200000000-2ffdc08c49952e135a862017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-000i-9000000000-8884b857c9582288f35a2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-052f-9000000000-7d2c0333bdce4dbabbc62017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0006-9000000000-9ab2a9480833026416282017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-000i-9400000000-c5ec3115706f6041b8682017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Negativesplash10-0udi-9000000000-89029b221f83859b721c2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Negativesplash10-014r-9000000000-ec63d377e53acd0b3f822021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Negativesplash10-000i-9000000000-1778c9be6683c7aaea832021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 6V, Negativesplash10-001r-7900000000-88fa19a8b55a2221ac332021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Negativesplash10-000i-9000000000-64994bb5102d568ae3ac2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Negativesplash10-000i-9300000000-087a8bb0014a4b98f2162021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Negativesplash10-000i-9100000000-be7bb3a98fa2fe29624c2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-ee7e50d3e19afde6d9972021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (Unknown) , Positivesplash10-052o-9000000000-663deab1ce6413c4859d2012-08-31View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-1900000000-2ccd8e2a515cf328e7872017-07-26View Spectrum
MSMass Spectrum (Electron Ionization)splash10-052o-9000000000-f308daa4e82c16019e0d2014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR1H NMR Spectrum (1D, 90 MHz, D2O, experimental)Not Available2014-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 25.16 MHz, D2O, experimental)Not Available2014-09-23View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Not Available2012-12-05View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityAccumulation of glutaric acid in the body has been shown to be toxic. The accumulation of glutaric acid ranging from slightly or intermittently elevated urinary glutaric acid to gross organic aciduria occurs in glutaric aciduria. Glutaric aciduria type 1 is an autosomal-recessive disorder resulting from a deficiency of mitochondrial glutaryl-CoA dehydrogenase which is involved in the metabolism of lysine, hydroxylysine, and tryptophan.
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesThis is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.
Minimum Risk LevelNot Available
Health EffectsChronically high levels of glutaric acid are associated with at least 3 inborn errors of metabolism including: Glutaric Aciduria Type I and Glutaric Aciduria Type III.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB03553
HMDB IDHMDB00661
PubChem Compound ID743
ChEMBL IDCHEMBL1162495
ChemSpider ID723
KEGG IDC00489
UniProt IDNot Available
OMIM ID
ChEBI ID17859
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDGUA
ACToR IDNot Available
Wikipedia LinkGlutaric acid
References
Synthesis Reference

Guiseppe Gigliotti, Jean-Michel Roul, “Process for the preparation of 3-methyl-3-hydroxy-glutaric acid.” U.S. Patent US4467108, issued June, 1980.

MSDSLink
General References
  1. Bishop FS, Liu JK, McCall TD, Brockmeyer DL: Glutaric aciduria type 1 presenting as bilateral subdural hematomas mimicking nonaccidental trauma. Case report and review of the literature. J Neurosurg. 2007 Mar;106(3 Suppl):222-6. [17465389 ]
  2. Muller E, Kolker S: Reduction of lysine intake while avoiding malnutrition--major goals and major problems in dietary treatment of glutaryl-CoA dehydrogenase deficiency. J Inherit Metab Dis. 2004;27(6):903-10. [15505398 ]
  3. Hoffmann GF, Trefz FK, Barth PG, Bohles HJ, Biggemann B, Bremer HJ, Christensen E, Frosch M, Hanefeld F, Hunneman DH, et al.: Glutaryl-coenzyme A dehydrogenase deficiency: a distinct encephalopathy. Pediatrics. 1991 Dec;88(6):1194-203. [1956737 ]
  4. Baric I, Wagner L, Feyh P, Liesert M, Buckel W, Hoffmann GF: Sensitivity and specificity of free and total glutaric acid and 3-hydroxyglutaric acid measurements by stable-isotope dilution assays for the diagnosis of glutaric aciduria type I. J Inherit Metab Dis. 1999 Dec;22(8):867-81. [10604139 ]
  5. Goodman SI, Stein DE, Schlesinger S, Christensen E, Schwartz M, Greenberg CR, Elpeleg ON: Glutaryl-CoA dehydrogenase mutations in glutaric acidemia (type I): review and report of thirty novel mutations. Hum Mutat. 1998;12(3):141-4. [9711871 ]
  6. 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 ]
  7. Goodman SI, Gallegos DA, Pullin CJ, Halpern B, Truscott RJ, Wise G, Wilcken B, Ryan ED, Whelen DT: Antenatal diagnosis of glutaric acidemia. Am J Hum Genet. 1980 Sep;32(5):695-9. [6893520 ]
  8. Shoemaker JD, Elliott WH: Automated screening of urine samples for carbohydrates, organic and amino acids after treatment with urease. J Chromatogr. 1991 Jan 2;562(1-2):125-38. [2026685 ]
  9. Jakobs C, Sweetman L, Wadman SK, Duran M, Saudubray JM, Nyhan WL: Prenatal diagnosis of glutaric aciduria type II by direct chemical analysis of dicarboxylic acids in amniotic fluid. Eur J Pediatr. 1984 Jan;141(3):153-7. [6698061 ]
  10. Whelan DT, Hill R, Ryan ED, Spate M: L-Glutaric acidemia: investigation of a patient and his family. Pediatrics. 1979 Jan;63(1):88-93. [440804 ]
  11. Hoffmann GF, Meier-Augenstein W, Stockler S, Surtees R, Rating D, Nyhan WL: Physiology and pathophysiology of organic acids in cerebrospinal fluid. J Inherit Metab Dis. 1993;16(4):648-69. [8412012 ]
  12. Singh I: Biochemistry of peroxisomes in health and disease. Mol Cell Biochem. 1997 Feb;167(1-2):1-29. [9059978 ]
  13. 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 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot 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