Human Metabolome Database Version 3.5

Showing metabocard for 2-Hydroxybutyric acid (HMDB00008)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-08-29 09:04:55 -0600
HMDB ID HMDB00008
Secondary Accession Numbers None
Metabolite Identification
Common Name 2-Hydroxybutyric acid
Description 2-Hydroxybutyric acid (alpha-hydroxybutyrate) is an organic acid derived from alpha-ketobutyrate. Alpha-ketobutyrate is produced by amino acid catabolism (threonine and methionine) and glutathione anabolism (cysteine formation pathway) and is metabolized to propionyl-CoA and carbon dioxide (PMID: 20526369 Link_out). 2-Hydroxybutyric acid is formed as a by-product during the formation of Alpha-ketobutyrate via a reaction catalyzed by lactate dehydrogenase (LDH) or alpha–hydroxybutyrate dehydrogenase (alpha–HBDH). Alpha-hydroxybutyric acid is primarily produced in mammalian hepatic tissues that catabolize L-threonine or synthesize glutathione. Oxidative stress or detoxification of xenobiotics in the liver can dramatically increase the rate of hepatic glutathione synthesis. Under such metabolic stress conditions, supplies of L-cysteine for glutathione synthesis become limiting, so homocysteine is diverted from the transmethylation pathway (which forms methionine) into the transsulfuration pathway (which forms cystathionine). 2-Hydroxybutyrate is released as a byproduct when cystathionine is cleaved to cysteine that is incorporated into glutathione. Chronic shifts in the rate of glutathione synthesis may be reflected by urinary excretion of 2-hydroxybutyrate. 2-hydroxybutyrate is an early marker for both insulin resistance and impaired glucose regulation that appears to arise due to increased lipid oxidation and oxidative stress (PMID: 20526369 Link_out). 2-Hydroxybutyric acid is often found in the urine of patients suffering from lactic acidosis and ketoacidosis. 2-Hydroxybutyric acid generally appears at high concentrations in situations related to deficient energy metabolism (e.g., birth asphyxia) and also in inherited metabolic diseases affecting the central nervous system during neonatal development, such as "cerebral" lactic acidosis, glutaric aciduria type II, dihydrolipoyl dehydrogenase (E3) deficiency, and propionic acidemia. More recently it has been noted that elevated levels of alpha-hydroxybutyrate in the plasma is a good marker for early stage type II diabetes (PMID:19166731 Link_out). It was concluded from studies done in the mid 1970's that an increased NADH2/NAD ratio was the most important factor for the production of 2-hydorxybutyric acid (PMID:168632 Link_out).
Structure Thumb
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  1. (RS)-2-Hydroxybutyrate
  2. (RS)-2-Hydroxybutyric acid
  3. 2-Hydroxy-Butanoate
  4. 2-Hydroxy-Butanoic acid
  5. 2-Hydroxy-DL-Butyrate
  6. 2-Hydroxy-DL-Butyric acid
  7. 2-Hydroxy-N-butyrate
  8. 2-Hydroxy-N-butyric acid
  9. 2-Hydroxybutanoate
  10. 2-Hydroxybutanoic acid
  11. 2-Hydroxybutyrate
  12. a-Hydroxy-N-butyrate
  13. a-Hydroxy-N-butyric acid
  14. a-Hydroxybutanoate
  15. a-Hydroxybutanoic acid
  16. a-Hydroxybutyrate
  17. a-Hydroxybutyric acid
  18. alpha-Hydroxy-N-butyrate
  19. alpha-Hydroxy-N-butyric acid
  20. alpha-Hydroxybutanoate
  21. alpha-Hydroxybutanoic acid
  22. alpha-Hydroxybutyrate
  23. alpha-Hydroxybutyric acid
  24. DL-2-Hydroxybutanoate
  25. DL-2-Hydroxybutanoic acid
  26. DL-a-Hydroxybutyrate
  27. DL-a-Hydroxybutyric acid
  28. DL-alpha-Hydroxybutyrate
  29. DL-alpha-Hydroxybutyric acid
Chemical Formula C4H8O3
Average Molecular Weight 104.1045
Monoisotopic Molecular Weight 104.047344122
IUPAC Name 2-hydroxybutanoic acid
Traditional IUPAC Name 2-hydroxybutyrate
CAS Registry Number 600-15-7
SMILES CCC(O)C(O)=O
InChI Identifier InChI=1S/C4H8O3/c1-2-3(5)4(6)7/h3,5H,2H2,1H3,(H,6,7)
InChI Key AFENDNXGAFYKQO-UHFFFAOYSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Organic Acids and Derivatives
Class Hydroxy Acids and Derivatives
Sub Class Short-chain Hydroxy Acids and Derivatives
Other Descriptors
  • 2-hydroxy monocarboxylic acid(ChEBI)
  • Aliphatic Acyclic Compounds
  • Alpha Hydroxy Acids and Derivatives
  • Hydroxy fatty acids(Lipidmaps)
  • Organic Compounds
  • Straight Chain Fatty Acids
  • hydroxybutyric acid(ChEBI)
Substituents
  • Carboxylic Acid
  • Secondary Alcohol
Direct Parent Short-chain Hydroxy Acids and Derivatives
Ontology
Status Detected and Quantified
Origin
  • Endogenous
Biofunction Not Available
Application Not Available
Cellular locations
  • Cytoplasm
  • Extracellular
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point 44.2 °C 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 484 g/L ALOGPS
LogP -0.16 ALOGPS
LogP 0.051 ChemAxon
LogS 0.67 ALOGPS
pKa (strongest acidic) 3.99 ChemAxon
pKa (strongest basic) -3.8 ChemAxon
Hydrogen Acceptor Count 3 ChemAxon
Hydrogen Donor Count 2 ChemAxon
Polar Surface Area 57.53 A2 ChemAxon
Rotatable Bond Count 2 ChemAxon
Refractivity 23.36 ChemAxon
Polarizability 9.98 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge -1 ChemAxon
Spectra
Gas-MS Spectrum
1H NMR Spectrum
MS/MS Spectrum Quattro_QQQ 10
MS/MS Spectrum Quattro_QQQ 25
MS/MS Spectrum Quattro_QQQ 40
MS/MS Spectrum EI-B (HITACHI RMU-7M)
MS/MS Spectrum GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies )
MS/MS Spectrum GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)
MS/MS Spectrum GC-MS
[1H,13C] 2D NMR Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Prostate
Pathways Not Available
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified
54.0 (8.0-80.0) uM Adult (>18 years old) Both Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
40.0 +/- 24.0 uM Not Specified Both Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
85.0 uM Adult (>18 years old) Both Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
37 +/- 21 (10 - 76) uM Children (1-13 year old) Both Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
35.0 +/- 24.0 uM Adult (>18 years old) Both Normal
Urine Detected and Quantified
2.445 (0-4.89) umol/mmol creatinine Not Specified Both Normal
Urine Detected and Quantified
2.8 (1.2-6.9) umol/mmol creatinine Adult (>18 years old) Both Comment Normal
Urine Detected and Quantified
5.0 (0.0-10.0) umol/mmol creatinine Infant (0-1 year old) Both Normal
  • Geigy Scient...
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Reference
Urine Detected and Quantified >25.0 umol/mmol creatinine Adult (>18 years old) Both Pyruvate dehydrogenase deficiency
  • OMIM 238331
Associated Disorders and Diseases
Disease References
Pyruvate dehydrogenase deficiency
    • OMIM 238331
      Associated OMIM IDs
      • 312170 Link_out (Pyruvate dehydrogenase deficiency)
      DrugBank ID Not Available
      DrugBank Metabolite ID Not Available
      Phenol Explorer Compound ID Not Available
      Phenol Explorer Metabolite ID Not Available
      FoodDB ID FDB021867
      KNApSAcK ID Not Available
      Chemspider ID 10792 Link_out
      KEGG Compound ID C05984 Link_out
      BioCyc ID CPD-3564 Link_out
      BiGG ID 47130 Link_out
      Wikipedia Link 2-Hydroxybutyric acid Link_out
      NuGOwiki Link HMDB00008 Link_out
      Metagene Link HMDB00008 Link_out
      METLIN ID 3783 Link_out
      PubChem Compound 11266 Link_out
      PDB ID Not Available
      ChEBI ID 1148 Link_out
      References
      Synthesis Reference Carlier, J. P.; Henry, C.; Lorin, V.; Rouffignat, K. Conversion of DL-threonine, D-threonine and 2-oxobutyrate into propionate and 2-hydroxybutyrate by Fusobacterium species. Letters in Applied Microbiology (1997), 25(5), 371-374.
      Material Safety Data Sheet (MSDS) Download (PDF)
      General References
      1. Sweatman BC, Farrant RD, Holmes E, Ghauri FY, Nicholson JK, Lindon JC: 600 MHz 1H-NMR spectroscopy of human cerebrospinal fluid: effects of sample manipulation and assignment of resonances. J Pharm Biomed Anal. 1993 Aug;11(8):651-64. Pubmed: 8257730 Link_out
      2. Landaas S, Pettersen JE: Clinical conditions associated with urinary excretion of 2-hydroxybutyric acid. Scand J Clin Lab Invest. 1975 May;35(3):259-66. Pubmed: 168632 Link_out
      3. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. Pubmed: 19212411 Link_out
      4. Li X, Xu Z, Lu X, Yang X, Yin P, Kong H, Yu Y, Xu G: Comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry for metabonomics: Biomarker discovery for diabetes mellitus. Anal Chim Acta. 2009 Feb 9;633(2):257-62. doi: 10.1016/j.aca.2008.11.058. Epub 2008 Dec 3. Pubmed: 19166731 Link_out
      5. Gall WE, Beebe K, Lawton KA, Adam KP, Mitchell MW, Nakhle PJ, Ryals JA, Milburn MV, Nannipieri M, Camastra S, Natali A, Ferrannini E: alpha-hydroxybutyrate is an early biomarker of insulin resistance and glucose intolerance in a nondiabetic population. PLoS One. 2010 May 28;5(5):e10883. doi: 10.1371/journal.pone.0010883. Pubmed: 20526369 Link_out
      6. Aldrich Library of FT-IR Spectra, 1st edn., 1985, 1, 548D
      7. Mori, K. et al., Tetrahedron, 1979, 35, 1601
      8. Levene, P.A. et al., J. Biol. Chem., 1941, 141, 391
      9. Duvillier, E., Ann. Chim. Phys., 1879, 17, 532
      10. Chenault, H.K. et al., J.O.C., 1987, 52, 2608
      11. Aldrich Library of 13C and 1H FT NMR Spectra, 1992, 1, 854B
      12. Horn, D.H.S. et al., J.C.S., 1954, 1460
      13. Wong, C.H. et al., J.O.C., 1985, 50, 1992

      Enzymes
      Name: Dihydrolipoyl dehydrogenase, mitochondrial
      Reactions: Not Available
      Gene Name: DLD
      Uniprot ID: P09622 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: L-lactate dehydrogenase A-like 6A
      Reactions:
      2-Hydroxybutyric acid + NAD unknown 2-Ketobutyric acid + NADH + Hydrogen Ion details
      Gene Name: LDHAL6A
      Uniprot ID: Q6ZMR3 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: L-lactate dehydrogenase B chain
      Reactions:
      2-Hydroxybutyric acid + NAD unknown 2-Ketobutyric acid + NADH + Hydrogen Ion details
      Gene Name: LDHB
      Uniprot ID: P07195 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: L-lactate dehydrogenase C chain
      Reactions:
      2-Hydroxybutyric acid + NAD unknown 2-Ketobutyric acid + NADH + Hydrogen Ion details
      Gene Name: LDHC
      Uniprot ID: P07864 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: L-lactate dehydrogenase A chain
      Reactions:
      2-Hydroxybutyric acid + NAD unknown 2-Ketobutyric acid + NADH + Hydrogen Ion details
      Gene Name: LDHA
      Uniprot ID: P00338 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: L-lactate dehydrogenase A-like 6B
      Reactions:
      2-Hydroxybutyric acid + NAD unknown 2-Ketobutyric acid + NADH + Hydrogen Ion details
      Gene Name: LDHAL6B
      Uniprot ID: Q9BYZ2 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA