GABAReceptorInhibitorgabareceptorinhibitor

(S)-3-Hydroxyisobutyric acid

By rofalproject
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 triangliar 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

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source (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 Formlia

C4H8O3 Average Molecliar Weight

104.1045 Monoisotopic Molecliar Weight

104.047344122 IUPAC Name

(2S)-3-hydroxy-2-methylpropanoic acid Traditional Name

(S)-3-hydroxyisobutyric 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 Description

This 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. Kingdom

Chemical entities Super Class

Organic compounds Class

Organic acids and derivatives Sub Class

Hydroxy acids and derivatives Direct Parent

Beta hydroxy acids and derivatives Alternative Parents

  • Monocarboxylic acids and derivatives
  • Carboxylic acids
  • Primary alcohols
  • Organic oxides
  • Hydrocarbon derivatives
  • Carbonyl compounds

    • 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

    • Molecliar Framework

    Aliphatic acyclic compounds External Descriptors

  • 3-hydroxyisobutyric acid (CHEBI:37373 )

    • Ontology Status

    Detected and Quantified Origin

  • Endogenous

    • Biofunction

    Not Available Application

    Not Available Cellliar locations

  • Cytoplasm
  • Mitochondria

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water SolubilityNot AvailableNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source Water Solubility571.0 mg/mLALOGPS 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 Number of Rings0ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key Predicted GC-MS

    Predicted GC-MS Spectrum – GC-MSNot Available LC-MS/MS

    LC-MS/MS Spectrum – Quattro_QQQ 10V, Negative (Annotated)splash10-0zfr-8900000000-b51c12e744025b833f31View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – Quattro_QQQ 25V, Negative (Annotated)splash10-0a4i-9100000000-0d72fcffff267d7bc980View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – Quattro_QQQ 40V, Negative (Annotated)splash10-0zfs-9400000000-b3b27a9cc8fd4ebe9eb1View in MoNA Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available 1D NMR

    1H NMR SpectrumNot Available 2D NMR

    [1H,13C] 2D NMR SpectrumNot Available

    Biological Properties Cellliar Locations

  • Cytoplasm
  • Mitochondria

    • Biofluid Locations

  • Blood
  • Cerebrospinal Fluid (CSF)
  • Saliva
  • Urine

    • Tissue Location

    Not Available Pathways

    Name SMPDB Link KEGG Link 2-Methyl-3-Hydroxybutryl CoA Dehydrogenase DeficiencySMP00137Not Available 3-Hydroxy-3-Methylglutaryl-CoA Lyase DeficiencySMP00138Not Available 3-hydroxyisobutyric acid dehydrogenase deficiencySMP00521Not Available 3-hydroxyisobutyric aciduriaSMP00522Not Available 3-Methylcrotonyl Coa Carboxylase Deficiency Type ISMP00237Not Available 3-Methylglutaconic Aciduria Type ISMP00139Not Available 3-Methylglutaconic Aciduria Type IIISMP00140Not Available 3-Methylglutaconic Aciduria Type IVSMP00141Not Available Beta-Ketothiolase DeficiencySMP00173Not Available Isobutyryl-coa dehydrogenase deficiencySMP00523Not Available Isovaleric acidemiaSMP00524Not Available Isovaleric AciduriaSMP00238Not Available Maple Syrup Urine DiseaseSMP00199Not Available Methylmalonate Semialdehyde Dehydrogenase DeficiencySMP00384Not Available Methylmalonic AciduriaSMP00200Not Available Propionic AcidemiaSMP00236Not Available Valine, Leucine and Isoleucine DegradationSMP00032map00280

    Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodDetected and Quantified21.0 +/- 2.0 uMAdlit (>18 years old)Both

    Normal

  • 2614280

    • details BloodDetected and Quantified20.0 (4.0-48.0) uMChildren (1-13 years old)BothNormal

  • 8412012

    • details Cerebrospinal Fluid (CSF)Detected and Quantified18.0 +/- 18.0 (0 – 36) uMAdlit (>18 years old)Not SpecifiedNormal

  • 8412012

    • details SalivaDetected and Quantified1.23 +/- 0.71 uMAdlit (>18 years old)BothNormal

  • Zerihun T. Dame, …

    • details UrineDetected and Quantified29.0 (11.8-59.8) umol/mmol creatinineAdlit (>18 years old)Both

    Normal

  • 24023812

    • 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 creatinineAdlit (>18 years old)BothNormal

  • 2702744

    • 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

  • 8087979

    • details UrineDetected and Quantified8.5 (4.9-17.1) umol/mmol creatinineChildren (1-13 years old)BothNormal

  • 8087979

    • details UrineDetected and Quantified7.8 (3.8-25.1) umol/mmol creatinineAdolescent (13-18 years old)BothNormal

  • 8087979

    • details UrineDetected and Quantified25.4 (10.2 -33.5) umol/mmol creatinineInfant (0-1 year old)BothNormal

  • 8087979

    • details

    Abnormal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodDetected and Quantified38.0 +/- 5.0 uMAdlit (>18 years old)Both

    Diabetes

  • 2614280

    • 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 creatinineAdlit (>18 years old)Both3-Hydroxyisobutyric aciduria

  • MetaGene

    • details UrineDetected and Quantified225.0 (60.0-390.0) umol/mmol creatinineChildren (1-13 years old)Both3-Hydroxyisobutyric Aciduria

  • MetaGene

    • 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 [Link]

    Associated OMIM IDs

  • 125853 (Diabetes mellitus type 2)
  • 236795 (3-Hydroxyisobutyric aciduria)

    • External Links 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 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

    Product: Ro 28-1675

    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 ]
    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, OGorman 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 Ion details
    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 Ion details
    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 + NADH details (S)-3-Hydroxyisobutyric acid + NAD → (S)-Methylmalonic acid semialdehyde + NADH + Hydrogen Ion details
    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 acid details (S)-3-Hydroxyisobutyryl-CoA + Water → Coenzyme A + (S)-3-Hydroxyisobutyric acid details

    PMID: 8392550

    By rofalproject

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