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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-10-09 18:43:42 UTC
HMDB IDHMDB00023
Secondary Accession Numbers
  • 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
  1. (S)-3-Hydroxyisobutyric acid
  2. 2-Methyl-L-(+)-Hydracrylate
  3. 2-Methyl-L-(+)-Hydracrylic acid
  4. 3-Hydroxy(iso)butyric acid
  5. 3-Hydroxy-2-methyl-(S)-Propanoate
  6. 3-Hydroxy-2-methyl-(S)-Propanoic acid
  7. 3-Hydroxy-2-methylpropanoate
  8. 3-Hydroxy-2-methylpropanoic acid
  9. 3-Hydroxy-isobutyrate
  10. 3-Hydroxyisobutyrate
  11. 3-Hydroxyisobutyric acid
Chemical FormulaC4H8O3
Average Molecular Weight104.1045
Monoisotopic Molecular Weight104.047344122
IUPAC Name(2S)-3-hydroxy-2-methylpropanoic acid
Traditional Name(2S)-3-hydroxy-2-methylpropanoic 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
KingdomOrganic Compounds
Super ClassOrganic Acids and Derivatives
ClassHydroxy Acids and Derivatives
Sub ClassBeta Hydroxy Acids and Derivatives
Other Descriptors
  • 3-hydroxyisobutyric acid(ChEBI)
  • Aliphatic Acyclic Compounds
Substituents
  • Carboxylic Acid
  • Primary Alcohol
Direct ParentBeta Hydroxy Acids and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
BiofunctionNot Available
ApplicationNot Available
Cellular locations
  • Cytoplasm
  • Mitochondria
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 Solubility571.0ALOGPS
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 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity23.62 m3·mol-1ChemAxon
Polarizability9.98 Å3ChemAxon
Spectra
SpectraMS/MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm
  • Mitochondria
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Saliva
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Valine, Leucine and Isoleucine DegradationSMP00032map00280
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
    • Dame, ZT. et al. ...
details
UrineDetected and Quantified29.0 (11.8-59.8) umol/mmol creatinineAdult (>18 years old)Both
Normal
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 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
UrineDetected and Quantified17.5 (2.0-33.0) umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified38.0 +/- 5.0 uMAdult (>18 years old)Both
Diabetes
details
UrineDetected and Quantified225.0 (60.0-390.0) umol/mmol creatinineChildren (1-13 years old)Both3-Hydroxyisobutyric Aciduria 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. MetaGene
Associated OMIM IDs
  • 125853 (Diabetes mellitus type 2)
  • 236795 (3-Hydroxyisobutyric aciduria)
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB021877
KNApSAcK IDNot Available
Chemspider ID389707
KEGG Compound IDC06001
BioCyc ID3-HYDROXY-ISOBUTYRATE
BiGG ID37034
Wikipedia LinkNot Available
NuGOwiki LinkHMDB00023
Metagene LinkHMDB00023
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