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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2017-12-20 20:29:24 UTC
HMDB IDHMDB0000023
Secondary Accession Numbers
  • HMDB00023
  • HMDB00435
Metabolite Identification
Common Name(S)-3-Hydroxyisobutyric acid
Description(S)-3-Hydroxyisobutyric (3-HIBA) acid is an organic acid. 3-HIBA is an intermediate in L-valine metabolism. 3-HIBA plays an important role in the diagnosis of the very rare inherited metabolic diseases 3-hydroxyisobutyric aciduria (OMIM 236795 ) and methylmalonic semialdehyde dehydrogenase deficiency (OMIM 603178 ). Patients with 3-hydroxyisobutyric aciduria excrete a significant amount of 3-HIBA not only during the acute stage but also when stable. 3-hydroxyisobutyric aciduria is caused by a 3-hydroxyisobutyryl-CoA dehydrogenase deficiency (PMID: 18329219 ). The severity of this disease varies from case to case. Most patients exhibit dysmorphic features, such as a small triangular face, a long philtrum, low set ears and micrognathia (PMID: 113770040 , 10686279 ). Lactic acidemia is also found in the affected patients, indicating that mitochondrial dysfunction is involved. 3-hydroxyisobutyrate appears to specifically inhibit the function of the respiratory chain complex I-III and mitochondrial creatine kinase (PMID: 18329219 ).
Structure
Thumb
Synonyms
ValueSource
(S)-3-Hydroxy-2-methylpropanoic acidChEBI
(S)-3-Hydroxy-2-methylpropionic acidChEBI
(S)-3-Hydroxy-2-methylpropanoateGenerator
(S)-3-HydroxyisobutyrateGenerator
(S)-3-Hydroxy-2-methylpropionateGenerator
2-Methyl-L-(+)-hydracrylateHMDB
2-Methyl-L-(+)-hydracrylic acidHMDB
3-Hydroxy(iso)butyric acidHMDB
3-Hydroxy-2-methyl-(S)-propanoateHMDB
3-Hydroxy-2-methyl-(S)-propanoic acidHMDB
3-Hydroxy-2-methylpropanoateHMDB
3-Hydroxy-2-methylpropanoic acidHMDB
3-Hydroxy-isobutyrateHMDB
3-HydroxyisobutyrateHMDB
3-Hydroxyisobutyric acidHMDB
Chemical FormulaC4H8O3
Average Molecular Weight104.1045
Monoisotopic Molecular Weight104.047344122
IUPAC Name(2S)-3-hydroxy-2-methylpropanoic acid
Traditional Name(S)-3-hydroxyisobutyric acid
CAS Registry Number2068-83-9
SMILES
C[C@@H](CO)C(O)=O
InChI Identifier
InChI=1S/C4H8O3/c1-3(2-5)4(6)7/h3,5H,2H2,1H3,(H,6,7)/t3-/m0/s1
InChI KeyDBXBTMSZEOQQDU-VKHMYHEASA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as beta hydroxy acids and derivatives. These are compounds containing a carboxylic acid substituted with a hydroxyl group on the C3 carbon atom.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic acids and derivatives
Sub ClassHydroxy acids and derivatives
Direct ParentBeta hydroxy acids and derivatives
Alternative Parents
Substituents
  • Beta-hydroxy acid
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

Source:

Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

Role

Indirect biological role:

Physiological effect

Health effect:

  Health condition:

    Metabolism and nutrition disorders:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility571 g/LALOGPS
logP-0.47ALOGPS
logP-0.26ChemAxon
logS0.74ALOGPS
pKa (Strongest Acidic)4.37ChemAxon
pKa (Strongest Basic)-2.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area57.53 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity23.62 m³·mol⁻¹ChemAxon
Polarizability9.98 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0ab9-9000000000-dd1c22f7a337d3289497View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00gr-9720000000-2a61310303ff8f2a7b42View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Negative (Annotated)splash10-0zfr-8900000000-b51c12e744025b833f31View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Negative (Annotated)splash10-0a4i-9100000000-0d72fcffff267d7bc980View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Negative (Annotated)splash10-0zfs-9400000000-b3b27a9cc8fd4ebe9eb1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-052r-9500000000-543c65dad21c233fc8a8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-052o-9000000000-7b7dcb34e28cb55ddafbView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-27deee4c6a386a43ebc3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-3900000000-a7aa709e1985355b4bd9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0pi0-9200000000-01a40fbe4d19283ef080View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4l-9000000000-622de763b5ea31ff4ee6View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Biological Properties
Cellular Locations
  • Cytoplasm
  • Mitochondria
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Saliva
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB/PathwhizKEGG
2-Methyl-3-Hydroxybutryl CoA Dehydrogenase DeficiencyPw000061Pw000061 greyscalePw000061 simpleNot Available
3-Hydroxy-3-Methylglutaryl-CoA Lyase DeficiencyPw000063Pw000063 greyscalePw000063 simpleNot Available
3-Methylcrotonyl Coa Carboxylase Deficiency Type IPw000065Pw000065 greyscalePw000065 simpleNot Available
3-Methylglutaconic Aciduria Type IPw000066Pw000066 greyscalePw000066 simpleNot Available
3-Methylglutaconic Aciduria Type IIIPw000067Pw000067 greyscalePw000067 simpleNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified21.0 +/- 2.0 uMAdult (>18 years old)Both
Normal
details
BloodDetected and Quantified20.0 (4.0-48.0) uMChildren (1-13 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified18.0 +/- 18.0 (0 - 36) uMAdult (>18 years old)Not SpecifiedNormal details
SalivaDetected and Quantified1.23 +/- 0.71 uMAdult (>18 years old)BothNormal
    • Zerihun T. Dame, ...
details
UrineDetected and Quantified29.0 (11.8-59.8) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified13.39 +/- 6.588 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected and Quantified13.0 (2.0-24.0) umol/mmol creatinineChildren (1-13 years old)BothNormal
    • Geigy Scientific ...
details
UrineDetected and Quantified11 (4.1-19) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified<95 umol/mmol creatinineChildren (1 - 18 years old)Both
Normal
    • BC Children's Hos...
details
UrineDetected and Quantified14.5 (5.5-28.7) umol/mmol creatinineNewborn (0-30 days old)BothNormal details
UrineDetected and Quantified8.5 (4.9-17.1) umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected and Quantified7.8 (3.8-25.1) umol/mmol creatinineAdolescent (13-18 years old)BothNormal details
UrineDetected and Quantified25.4 (10.2 -33.5) umol/mmol creatinineInfant (0-1 year old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified38.0 +/- 5.0 uMAdult (>18 years old)Both
Diabetes
details
UrineDetected and Quantified12.772 +/- 10.179 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified17.5 (2.0-33.0) umol/mmol creatinineAdult (>18 years old)Both3-Hydroxyisobutyric aciduria
    • MetaGene: Metabol...
details
UrineDetected and Quantified225.0 (60.0-390.0) umol/mmol creatinineChildren (1-13 years old)Both3-Hydroxyisobutyric Aciduria
    • MetaGene: Metabol...
details
Associated Disorders and Diseases
Disease References
Diabetes mellitus type 2
  1. Avogaro A, Bier DM: Contribution of 3-hydroxyisobutyrate to the measurement of 3-hydroxybutyrate in human plasma: comparison of enzymatic and gas-liquid chromatography-mass spectrometry assays in normal and in diabetic subjects. J Lipid Res. 1989 Nov;30(11):1811-7. [PubMed:2614280 ]
3-Hydroxyisobutyric aciduria
  1. G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
Associated OMIM IDs
  • 125853 (Diabetes mellitus type 2)
  • 236795 (3-Hydroxyisobutyric aciduria)
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDFDB021877
KNApSAcK IDNot Available
Chemspider ID389707
KEGG Compound IDC06001
BioCyc ID3-HYDROXY-ISOBUTYRATE
BiGG ID37034
Wikipedia LinkNot Available
METLIN ID483
PubChem Compound440873
PDB IDNot Available
ChEBI ID37373
References
Synthesis ReferenceRobison, Robert S.; Doremus, Michael G.L-(+)-b-Hydroxyisobutyric acid by fermentation. U.S. (1986), 5 pp.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Yoshida I, Sweetman L, Kulovich S, Nyhan WL, Robinson BH: Effect of lipoic acid in a patient with defective activity of pyruvate dehydrogenase, 2-oxoglutarate dehydrogenase, and branched-chain keto acid dehydrogenase. Pediatr Res. 1990 Jan;27(1):75-9. [PubMed:2104971 ]
  2. Liebich HM, Dotzauer A, Tetschner B: Gas chromatographic determination of oxo- and hydroxycarboxylic acids in serum and urine of diabetic and normal subjects. J Chromatogr. 1989 May 12;468:157-65. [PubMed:2732286 ]
  3. 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. [PubMed:10686279 ]
  4. Chitayat D, Meagher-Villemure K, Mamer OA, O'Gorman A, Hoar DI, Silver K, Scriver CR: Brain dysgenesis and congenital intracerebral calcification associated with 3-hydroxyisobutyric aciduria. J Pediatr. 1992 Jul;121(1):86-9. [PubMed:1625099 ]
  5. Landaas S: Accumulation of 3-hydroxyisobutyric acid, 2-methyl-3-hydroxybutyric acid and 3-hydroxyisovaleric acid in ketoacidosis. Clin Chim Acta. 1975 Oct 15;64(2):143-54. [PubMed:126826 ]
  6. 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. [PubMed:8412012 ]

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
Not Available
Gene Name:
EHHADH
Uniprot ID:
Q08426
Molecular weight:
69153.26
Reactions
(S)-3-Hydroxyisobutyric acid + NAD → (S)-Methylmalonic acid semialdehyde + NADH + Hydrogen Iondetails
General function:
Involved in 3-hydroxyacyl-CoA dehydrogenase activity
Specific function:
Plays an essential role in the mitochondrial beta-oxidation of short chain fatty acids. Exerts it highest activity toward 3-hydroxybutyryl-CoA.
Gene Name:
HADH
Uniprot ID:
Q16836
Molecular weight:
36035.11
Reactions
(S)-3-Hydroxyisobutyric acid + NAD → (S)-Methylmalonic acid semialdehyde + NADH + Hydrogen Iondetails
General function:
Involved in 3-hydroxyisobutyrate dehydrogenase activity
Specific function:
Not Available
Gene Name:
HIBADH
Uniprot ID:
P31937
Molecular weight:
35328.515
Reactions
(S)-3-Hydroxyisobutyric acid + NAD → 2-Methyl-3-oxopropanoic acid + NADHdetails
(S)-3-Hydroxyisobutyric acid + NAD → (S)-Methylmalonic acid semialdehyde + NADH + Hydrogen Iondetails
General function:
Involved in catalytic activity
Specific function:
Hydrolyzes 3-hydroxyisobutyryl-CoA (HIBYL-CoA), a saline catabolite. Has high activity toward isobutyryl-CoA. Could be an isobutyryl-CoA dehydrogenase that functions in valine catabolism. Also hydrolyzes 3-hydroxypropanoyl-CoA.
Gene Name:
HIBCH
Uniprot ID:
Q6NVY1
Molecular weight:
43481.935
Reactions
(S)-3-Hydroxyisobutyryl-CoA + Water → Coenzyme A + (S)-3-Hydroxyisobutyric aciddetails
(S)-3-Hydroxyisobutyryl-CoA + Water → Coenzyme A + (S)-3-Hydroxyisobutyric aciddetails