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Human Metabolome Database Version 3.5

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

• Identification
• Taxonomy
• Ontology
• Physical properties
• Spectra
• Biological properties
• Concentrations
• Links
• References

enzymes (3)

• Blood
• Urine

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 ) 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	Download: MOL | SDF | SMILES | InChI Display: 2D Structure | 3D Structure
Synonyms	(S)-3-Hydroxyisobutyric acid 2-Methyl-L-(+)-Hydracrylate 2-Methyl-L-(+)-Hydracrylic acid 3-Hydroxy(iso)butyric acid 3-Hydroxy-2-methyl-(S)-Propanoate 3-Hydroxy-2-methyl-(S)-Propanoic acid 3-Hydroxy-2-methylpropanoate 3-Hydroxy-2-methylpropanoic acid 3-Hydroxy-isobutyrate 3-Hydroxyisobutyrate 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
Normal Concentrations
	Biofluid Status Value Age Sex Condition Comments Blood Detected and Quantified 21.0 +/- 2.0 uM Adult (>18 years old) Both Normal Concentration refers to racemic mixture Blood Detected and Quantified 20.0 (4.0-48.0) uM Children (1-13 year old) Both Normal Not Available Cerebrospinal Fluid (CSF) Detected and Quantified 18.0 +/- 18.0 (0 - 36) uM Adult (>18 years old) Not Specified Normal Not Available Urine Detected and Quantified 29.0 (11.8-59.8) umol/mmol creatinine Adult (>18 years old) Both Normal by GC-MS Urine Detected and Quantified 13.0 (2.0-24.0) umol/mmol creatinine Children (1-13 year old) Both Normal Not Available Urine Detected and Quantified 11 (4.1-19) umol/mmol creatinine Adult (>18 years old) Both Normal Not Available Urine Detected and Quantified 14.5 (5.5-28.7) umol/mmol creatinine Newborn (0-30 days old) Both Normal Not Available Urine Detected and Quantified 8.5 (4.9-17.1) umol/mmol creatinine Children (1-13 year old) Both Normal Not Available Urine Detected and Quantified 7.8 (3.8-25.1) umol/mmol creatinine Adolescent (13-18 years old) Both Normal Not Available Urine Detected and Quantified 25.4 (10.2 -33.5) umol/mmol creatinine Infant (0-1 year old) Both Normal Not Available Urine Detected and Quantified 17.5 (2.0-33.0) umol/mmol creatinine Adult (>18 years old) Both Normal Not Available
Abnormal Concentrations
	Biofluid Status Value Age Sex Condition Comments Blood Detected and Quantified 38.0 +/- 5.0 uM Adult (>18 years old) Both Diabetes Concentration refers to racemic mixture Urine Detected and Quantified 225.0 (60.0-390.0) umol/mmol creatinine Adult (>18 years old) Both 3-Hydroxyisobutyric Aciduria Not Available
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 3-Hydroxyisobutyric aciduria http://www.metagene.de/program/d.prg?mp=3-HYDROXYISOBUTYRIC%20ACIDURIA
Associated OMIM IDs	125853 (Diabetes mellitus type 2) 236795 (3-Hydroxyisobutyric aciduria)
External Links
DrugBank 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
KEGG Compound ID	C06001
BioCyc ID	3-HYDROXY-ISOBUTYRATE
BiGG ID	37034
Wikipedia Link	Not Available
NuGOwiki Link	HMDB00023
Metagene Link	HMDB00023
METLIN ID	483
PubChem Compound	440873
PDB ID	Not Available
ChEBI ID	37373
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	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 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 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 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 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 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

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Enzymes
Name: Peroxisomal bifunctional enzyme Reactions: (3Z)-dodec-3-enoyl-CoA = (2E)-dodec-2-enoyl-CoA [RN:R04100] Gene Name: EHHADH Uniprot ID: Q08426 Protein Sequence: FASTA Gene Sequence: FASTA
Name: 3-hydroxyisobutyrate dehydrogenase, mitochondrial Reactions: 3-hydroxy-2-methylpropanoate + NAD+ = 2-methyl-3-oxopropanoate + NADH + H+ [RN:R02047] Gene Name: HIBADH Uniprot ID: P31937 Protein Sequence: FASTA Gene Sequence: FASTA
Name: 3-hydroxyisobutyryl-CoA hydrolase, mitochondrial Reactions: 3-hydroxy-2-methylpropanoyl-CoA + H2O = CoA + 3-hydroxy-2-methylpropanoate [RN:R03352] Gene Name: HIBCH Uniprot ID: Q6NVY1 Protein Sequence: FASTA Gene Sequence: FASTA

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government.