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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-10-29 20:41:48 UTC
HMDB IDHMDB00008
Secondary Accession NumbersNone
Metabolite Identification
Common Name2-Hydroxybutyric acid
Description2-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 ). 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 ). 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 ). 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 ).
Structure
Thumb
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 FormulaC4H8O3
Average Molecular Weight104.1045
Monoisotopic Molecular Weight104.047344122
IUPAC Name2-hydroxybutanoic acid
Traditional Name2-hydroxybutyrate
CAS Registry Number600-15-7
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 KeyAFENDNXGAFYKQO-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassOrganic Acids and Derivatives
ClassHydroxy Acids and Derivatives
Sub ClassShort-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 ParentShort-chain Hydroxy Acids and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
BiofunctionNot Available
ApplicationNot Available
Cellular locations
  • Cytoplasm
  • Extracellular
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point44.2 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility484.0ALOGPS
logP-0.16ALOGPS
logP0.051ChemAxon
logS0.67ALOGPS
pKa (Strongest Acidic)3.99ChemAxon
pKa (Strongest Basic)-3.8ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area57.53 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity23.36 m3·mol-1ChemAxon
Polarizability9.98 Å3ChemAxon
Spectra
SpectraGC-MSMS/MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Saliva
  • Urine
Tissue Location
  • Prostate
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified54.0 (8.0-80.0) uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified40.0 +/- 24.0 uMNot SpecifiedBothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified85.0 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified37 +/- 21 (10 - 76) uMChildren (1-13 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified35.0 +/- 24.0 uMAdult (>18 years old)BothNormal details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected and Quantified10.42 +/- 9.20 uMAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified2.445 (0-4.89) umol/mmol creatinineNot SpecifiedBothNormal details
UrineDetected and Quantified2.8 (1.2-6.9) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified5.0 (0.0-10.0) umol/mmol creatinineInfant (0-1 year old)BothNormal
    • Geigy Scientific ...
details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
SalivaDetected and Quantified7.26 +/- 4.47 uMAdult (>18 years old)MaleAlzheimer's disease details
SalivaDetected and Quantified7.30 +/- 1.32 uMAdult (>18 years old)MaleFrontotemporal lobe dementia details
SalivaDetected and Quantified8.12 +/- 5.32 uMAdult (>18 years old)BothLewy body disease details
UrineDetected and Quantified>25.0 umol/mmol creatinineAdult (>18 years old)BothPyruvate dehydrogenase deficiency
    • OMIM 238331
details
Associated Disorders and Diseases
Disease References
Pyruvate dehydrogenase deficiency
  1. OMIM 238331
Associated OMIM IDs
  • 312170 (Pyruvate dehydrogenase deficiency)
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB021867
KNApSAcK IDNot Available
Chemspider ID10792
KEGG Compound IDC05984
BioCyc IDCPD-3564
BiGG ID47130
Wikipedia Link2-Hydroxybutyric acid
NuGOwiki LinkHMDB00008
Metagene LinkHMDB00008
METLIN ID3783
PubChem Compound11266
PDB IDNot Available
ChEBI ID1148
References
Synthesis ReferenceCarlier, 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
  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
  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
  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
  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
  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

General function:
Involved in oxidoreductase activity
Specific function:
Lipoamide dehydrogenase is a component of the glycine cleavage system as well as of the alpha-ketoacid dehydrogenase complexes. Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction.
Gene Name:
DLD
Uniprot ID:
P09622
Molecular weight:
54176.91
References
  1. Kuhara T, Shinka T, Inoue Y, Matsumoto M, Yoshino M, Sakaguchi Y, Matsumoto I: Studies of urinary organic acid profiles of a patient with dihydrolipoyl dehydrogenase deficiency. Clin Chim Acta. 1983 Sep 30;133(2):133-40. Pubmed: 6688766
General function:
Involved in oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
Specific function:
Displays an lactate dehydrogenase activity. Significantly increases the transcriptional activity of JUN, when overexpressed.
Gene Name:
LDHAL6A
Uniprot ID:
Q6ZMR3
Molecular weight:
36507.015
Reactions
2-Hydroxybutyric acid + NAD → 2-Ketobutyric acid + NADH + Hydrogen Iondetails
General function:
Involved in oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
Specific function:
Not Available
Gene Name:
LDHB
Uniprot ID:
P07195
Molecular weight:
36638.225
Reactions
2-Hydroxybutyric acid + NAD → 2-Ketobutyric acid + NADH + Hydrogen Iondetails
General function:
Involved in oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
Specific function:
Possible role in sperm motility.
Gene Name:
LDHC
Uniprot ID:
P07864
Molecular weight:
36310.965
Reactions
2-Hydroxybutyric acid + NAD → 2-Ketobutyric acid + NADH + Hydrogen Iondetails
General function:
Involved in oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
Specific function:
Not Available
Gene Name:
LDHA
Uniprot ID:
P00338
Molecular weight:
30204.975
Reactions
2-Hydroxybutyric acid + NAD → 2-Ketobutyric acid + NADH + Hydrogen Iondetails
General function:
Involved in oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
Specific function:
Not Available
Gene Name:
LDHAL6B
Uniprot ID:
Q9BYZ2
Molecular weight:
41942.53
Reactions
2-Hydroxybutyric acid + NAD → 2-Ketobutyric acid + NADH + Hydrogen Iondetails