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Record Information
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2018-02-27 23:35:34 UTC
Secondary Accession Numbers
  • HMDB00428
Metabolite Identification
Common Name3-Hydroxyglutaric acid
Description3-Hydroxyglutaric acid is a member of the class of compounds known as dicarboxylic acids and derivatives. These are organic compounds containing exactly two carboxylic acid groups. 3-Hydroxyglutaric acid is soluble (in water) and a weakly acidic compound (based on its pKa). When present in sufficiently high levels, 3-hydroxyglutaric acid can act as 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 3-hydroxyglutaric 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 3-hydroxyglutaric 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 or glutaric acidemia. 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. It is believed that the excretion of 3-hydroxyglutaric acid is increased during ketosis, which occurs during glutaryl-CoA dehydrogenase deficiency.
3-Hydroxy-glutaric acidHMDB
3-Hydroxypentanedioic acidCAS
2,4-Dideoxypentaric acidCAS
β-Hydroxyglutaric acidCAS
beta-Hydroxyglutaric acidCAS
Chemical FormulaC5H8O5
Average Molecular Weight148.114
Monoisotopic Molecular Weight148.037173366
IUPAC Name3-hydroxypentanedioic acid
Traditional Name3-hydroxyglutaric acid
CAS Registry Number638-18-6
InChI Identifier
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as beta hydroxy acids and derivatives. These are compounds containing a carboxylic acid substituted with a hydroxyl group on the C3 carbon atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassHydroxy acids and derivatives
Sub ClassBeta hydroxy acids and derivatives
Direct ParentBeta hydroxy acids and derivatives
Alternative Parents
  • Short-chain hydroxy acid
  • Beta-hydroxy acid
  • Fatty acid
  • Dicarboxylic acid or derivatives
  • Secondary alcohol
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External DescriptorsNot Available
Physiological effect

Health effect:

  Health condition:

    Metabolism and nutrition disorders:


Biological location:


  Biofluid and excreta:

  Cell and elements:




Industrial application:

  Pharmaceutical industry:

Physical Properties
Experimental Properties
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
Water Solubility172 g/LALOGPS
pKa (Strongest Acidic)3.52ChemAxon
pKa (Strongest Basic)-2.9ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area94.83 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity29.5 m³·mol⁻¹ChemAxon
Polarizability12.81 ųChemAxon
Number of Rings0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0536-9200000000-95922095d2aa1db75f8bView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positivesplash10-00gs-9081000000-c273d86d7f22986f4bcdView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-01qa-1900000000-83e00bd7b92b7f2f9832View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01qi-5900000000-da4f8a92eae4f7ae9a73View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-9000000000-a255aedbfaa3bce837b8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-2900000000-6ea9c60bf78cda297a39View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0pbj-9800000000-db9f014d4e5dce1cc78fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9100000000-89edd1cbe710cf97835dView in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Biological Properties
Cellular Locations
  • Cytoplasm
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Neuron
PathwaysNot Available
Normal Concentrations
BloodDetected and Quantified0.15 +/- 0.08 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified<0.2 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.07 +/- 0.03 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified22-67 uMNot SpecifiedNot SpecifiedNormal details
UrineDetected and Quantified0-3 umol/mmol creatinineNewborn (0-30 days old)MaleNormal details
UrineDetected and Quantified<11.51 umol/mmol creatinineChildren (1 - 18 years old)Both
    • BC Children's Hos...
Abnormal Concentrations
BloodDetected and Quantified1.8 uMNewborn (0-30 days old)MaleGlutaric aciduria I details
Cerebrospinal Fluid (CSF)Detected and Quantified4450 uMNot AvailableNot Specified
Glutaryl-CoA dehydrogenase deficiency (GDHD)
Cerebrospinal Fluid (CSF)Detected and Quantified4450 uMChildren (1-13 years old)Not SpecifiedGlutaric acid excretion above 100 mmol/mol creatinine details
Cerebrospinal Fluid (CSF)Detected and Quantified2.2 uMNewborn (0-30 days old)MaleGlutaric aciduria I details
UrineDetected and Quantified3.68 umol/mmol creatinineAdolescent (13-18 years old)FemaleGlutaric aciduria I details
UrineDetected and Quantified590 umol/mmol creatinineNewborn (0-30 days old)MaleGlutaric aciduria I details
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB04594
Phenol Explorer Compound IDNot Available
FoodDB IDFDB022040
KNApSAcK IDNot Available
Chemspider ID158277
KEGG Compound IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
PubChem Compound181976
ChEBI IDNot Available
Synthesis ReferenceArnaud, Nathalie; Picard, Claude; Cazaux, Louis; Tisnes, Pierre. Synthesis of macrocyclic polyhydroxy tetralactams derived from L-tartaric acid and b-hydroxyglutaric acid. Tetrahedron (1997), 53(40), 13757-13768.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. 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. [PubMed:10604139 ]
  2. Kolker S, Hoffmann GF, Schor DS, Feyh P, Wagner L, Jeffrey I, Pourfarzam M, Okun JG, Zschocke J, Baric I, Bain MD, Jakobs C, Chalmers RA: Glutaryl-CoA dehydrogenase deficiency: region-specific analysis of organic acids and acylcarnitines in post mortem brain predicts vulnerability of the putamen. Neuropediatrics. 2003 Jun;34(5):253-60. [PubMed:14598231 ]
  3. Wajner M, Kolker S, Souza DO, Hoffmann GF, de Mello CF: Modulation of glutamatergic and GABAergic neurotransmission in glutaryl-CoA dehydrogenase deficiency. J Inherit Metab Dis. 2004;27(6):825-8. [PubMed:15505388 ]
  4. Nyhan WL, Zschocke J, Hoffmann G, Stein DE, Bao L, Goodman S: Glutaryl-CoA dehydrogenase deficiency presenting as 3-hydroxyglutaric aciduria. Mol Genet Metab. 1999 Mar;66(3):199-204. [PubMed:10066389 ]
  5. Molven A, Matre GE, Duran M, Wanders RJ, Rishaug U, Njolstad PR, Jellum E, Sovik O: Familial hyperinsulinemic hypoglycemia caused by a defect in the SCHAD enzyme of mitochondrial fatty acid oxidation. Diabetes. 2004 Jan;53(1):221-7. [PubMed:14693719 ]
  6. Haworth JC, Booth FA, Chudley AE, deGroot GW, Dilling LA, Goodman SI, Greenberg CR, Mallory CJ, McClarty BM, Seshia SS, et al.: Phenotypic variability in glutaric aciduria type I: Report of fourteen cases in five Canadian Indian kindreds. J Pediatr. 1991 Jan;118(1):52-8. [PubMed:1986098 ]
  7. Sauer SW, Okun JG, Fricker G, Mahringer A, Muller I, Crnic LR, Muhlhausen C, Hoffmann GF, Horster F, Goodman SI, Harding CO, Koeller DM, Kolker S: Intracerebral accumulation of glutaric and 3-hydroxyglutaric acids secondary to limited flux across the blood-brain barrier constitute a biochemical risk factor for neurodegeneration in glutaryl-CoA dehydrogenase deficiency. J Neurochem. 2006 May;97(3):899-910. Epub 2006 Mar 29. [PubMed:16573641 ]