Human Metabolome Database Version 3.5

Showing metabocard for (S)-3-Hydroxyisobutyric acid (HMDB00023)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-02-08 17:07:46 -0700
HMDB ID HMDB00023
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 Link_out) and methylmalonic semialdehyde dehydrogenase deficiency (OMIM 603178 Link_out). 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 Link_out). 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 Link_out, 10686279 Link_out). 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 Link_out).
Structure Thumb
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
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 Formula C4H8O3
Average Molecular Weight 104.1045
Monoisotopic Molecular Weight 104.047344122
IUPAC Name (2S)-3-hydroxy-2-methylpropanoic acid
Traditional IUPAC Name (2S)-3-hydroxy-2-methylpropanoic acid
CAS Registry Number 2068-83-9
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 Key DBXBTMSZEOQQDU-VKHMYHEASA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Organic Acids and Derivatives
Class Hydroxy Acids and Derivatives
Sub Class Beta Hydroxy Acids and Derivatives
Other Descriptors
  • 3-hydroxyisobutyric acid(ChEBI)
  • Aliphatic Acyclic Compounds
Substituents
  • Carboxylic Acid
  • Primary Alcohol
Direct Parent Beta Hydroxy Acids and Derivatives
Ontology
Status Detected and Quantified
Origin
  • Endogenous
Biofunction Not Available
Application Not Available
Cellular locations
  • Cytoplasm
  • Mitochondria
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point Not Available Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
Water Solubility 571 g/L ALOGPS
LogP -0.47 ALOGPS
LogP -0.26 ChemAxon
LogS 0.74 ALOGPS
pKa (strongest acidic) 4.37 ChemAxon
pKa (strongest basic) -2.7 ChemAxon
Hydrogen Acceptor Count 3 ChemAxon
Hydrogen Donor Count 2 ChemAxon
Polar Surface Area 57.53 A2 ChemAxon
Rotatable Bond Count 2 ChemAxon
Refractivity 23.62 ChemAxon
Polarizability 9.98 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge -1 ChemAxon
Spectra
1H NMR Spectrum
MS/MS Spectrum Quattro_QQQ 10
MS/MS Spectrum Quattro_QQQ 25
MS/MS Spectrum Quattro_QQQ 40
[1H,13C] 2D NMR Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Mitochondria
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location Not Available
Pathways
Name SMPDB Link KEGG Link
Valine, Leucine and Isoleucine Degradation SMP00032 map00280 Link_out
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified
21.0 +/- 2.0 uM Adult (>18 years old) Both Comment Normal
Blood Detected and Quantified
20.0 (4.0-48.0) uM Children (1-13 year old) Both Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
18.0 +/- 18.0 (0 - 36) uM Adult (>18 years old) Not Specified Normal
Urine Detected and Quantified
29.0 (11.8-59.8) umol/mmol creatinine Adult (>18 years old) Both Comment Normal
Urine Detected and Quantified
13.0 (2.0-24.0) umol/mmol creatinine Children (1-13 year old) Both Normal
  • Geigy Scient...
Urine Detected and Quantified
11 (4.1-19) umol/mmol creatinine Adult (>18 years old) Both Normal
Urine Detected and Quantified
14.5 (5.5-28.7) umol/mmol creatinine Newborn (0-30 days old) Both Normal
Urine Detected and Quantified
8.5 (4.9-17.1) umol/mmol creatinine Children (1-13 year old) Both Normal
Urine Detected and Quantified
7.8 (3.8-25.1) umol/mmol creatinine Adolescent (13-18 years old) Both Normal
Urine Detected and Quantified
25.4 (10.2 -33.5) umol/mmol creatinine Infant (0-1 year old) Both Normal
Urine Detected and Quantified
17.5 (2.0-33.0) umol/mmol creatinine Adult (>18 years old) Both Normal
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified 38.0 +/- 5.0 uM Adult (>18 years old) Both Comment Diabetes
Urine Detected and Quantified 225.0 (60.0-390.0) umol/mmol creatinine Children (1-13 year old) Both 3-Hydroxyisobutyric Aciduria
Associated Disorders and Diseases
Disease References
Diabetes mellitus type 2
  • 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 Link_out
      3-Hydroxyisobutyric aciduria
          Associated OMIM IDs
          • 125853 Link_out (Diabetes mellitus type 2)
          • 236795 Link_out (3-Hydroxyisobutyric aciduria)
          DrugBank ID Not Available
          DrugBank Metabolite ID Not Available
          Phenol Explorer Compound ID Not Available
          Phenol Explorer Metabolite ID Not Available
          FoodDB ID FDB021877
          KNApSAcK ID Not Available
          Chemspider ID 389707 Link_out
          KEGG Compound ID C06001 Link_out
          BioCyc ID 3-HYDROXY-ISOBUTYRATE Link_out
          BiGG ID 37034 Link_out
          Wikipedia Link Not Available
          NuGOwiki Link HMDB00023 Link_out
          Metagene Link HMDB00023 Link_out
          METLIN ID 483 Link_out
          PubChem Compound 440873 Link_out
          PDB ID Not Available
          ChEBI ID 37373 Link_out
          References
          Synthesis Reference Robison, 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 Link_out
          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 Link_out
          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 Link_out
          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 Link_out
          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 Link_out
          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 Link_out

          Enzymes
          Name: Peroxisomal bifunctional enzyme
          Reactions:
          (S)-3-Hydroxyisobutyric acid + NAD unknown (S)-Methylmalonic acid semialdehyde + NADH + Hydrogen Ion details
          Gene Name: EHHADH
          Uniprot ID: Q08426 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          Name: Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial
          Reactions:
          (S)-3-Hydroxyisobutyric acid + NAD unknown (S)-Methylmalonic acid semialdehyde + NADH + Hydrogen Ion details
          Gene Name: HADH
          Uniprot ID: Q16836 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          Name: 3-hydroxyisobutyrate dehydrogenase, mitochondrial
          Reactions:
          (S)-3-Hydroxyisobutyric acid + NAD unknown 2-Methyl-3-oxopropanoic acid + NADH details
          (S)-3-Hydroxyisobutyric acid + NAD unknown (S)-Methylmalonic acid semialdehyde + NADH + Hydrogen Ion details
          Gene Name: HIBADH
          Uniprot ID: P31937 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          Name: 3-hydroxyisobutyryl-CoA hydrolase, mitochondrial
          Reactions:
          (S)-3-Hydroxyisobutyryl-CoA + Water unknown Coenzyme A + (S)-3-Hydroxyisobutyric acid details
          (S)-3-Hydroxyisobutyryl-CoA + Water unknown Coenzyme A + (S)-3-Hydroxyisobutyric acid details
          Gene Name: HIBCH
          Uniprot ID: Q6NVY1 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA