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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-10-09 18:43:36 UTC
HMDB IDHMDB00060
Secondary Accession NumbersNone
Metabolite Identification
Common NameAcetoacetic acid
DescriptionIt is a weak organic acid and can be produced in the human liver under certain conditions of poor metabolism leading to excessive fatty acid breakdown (diabetes mellitus leading to diabetic ketoacidosis), it is then partially converted to acetone by decarboxylation and excreted either in urine or through respiration. Persistent mild hyperketonemia is a common finding in newborns. These compounds serve as an indispensable source of energy for extrahepatic tissues, especially the brain and lung of developing rats. Another important function of ketone bodies is to provide acetoacetyl-CoA and acetyl-CoA for synthesis of cholesterol, fatty acids, and complex lipids. During the early postnatal period, acetoacetate (AcAc) and beta-hydroxybutyrate are preferred over glucose as substrates for synthesis of phospholipids and sphingolipids in accord with requirements for brain growth and myelination. Thus, during the first 2 wk of postnatal development, when the accumulation of cholesterol and phospholipids accelerates, the proportion of ketone bodies incorporated into these lipids increases. On the other hand, an increased proportion of ketone bodies are utilized for cerebroside synthesis during the period of active myelination. In the lung, AcAc serves better than glucose as a precursor for the synthesis of lung phospholipids. The synthesized lipids, particularly dipalmityl phosphatidylcholine, are incorporated into surfactant, and thus have a potential role in supplying adequate surfactant lipids to maintain lung function during the early days of life. (PMID 3884391 ) The acid is also present in the metabolism of those undergoing starvation or prolonged physical exertion as part of gluconeogenesis. When ketone bodies are measured by way of urine concentration, acetoacetic acid, along with beta-hydroxybutyric acid or acetone, is what is detected.
Structure
Thumb
Synonyms
  1. 3-Ketobutyrate
  2. 3-Ketobutyric acid
  3. 3-Oxo-butanoate
  4. 3-Oxo-butanoic acid
  5. 3-Oxobutyrate
  6. 3-Oxobutyric acid
  7. Acetoacetate
  8. Diacetate
  9. Diacetic acid
Chemical FormulaC4H6O3
Average Molecular Weight102.0886
Monoisotopic Molecular Weight102.031694058
IUPAC Name3-oxobutanoic acid
Traditional Nameacetoacetic acid
CAS Registry Number541-50-4
SMILES
CC(=O)CC(O)=O
InChI Identifier
InChI=1S/C4H6O3/c1-3(5)2-4(6)7/h2H2,1H3,(H,6,7)
InChI KeyWDJHALXBUFZDSR-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassOrganic Acids and Derivatives
ClassKeto-Acids and Derivatives
Sub ClassBeta Keto-Acids and Derivatives
Other Descriptors
  • 3-oxo monocarboxylic acid(ChEBI)
  • Aliphatic Acyclic Compounds
  • Organic Compounds
  • Oxo fatty acids(KEGG)
  • Oxo fatty acids(Lipidmaps)
  • Straight Chain Fatty Acids
  • short-chain fatty acid(ChEBI)
  • straight-chain saturated fatty acid(ChEBI)
Substituents
  • Carboxylic Acid
  • Ketone
  • Short Chain Keto Acid
Direct ParentBeta Keto-Acids and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Butanoate metabolism
  • Component of Tyrosine metabolism
ApplicationNot Available
Cellular locations
  • Cytoplasm
  • Extracellular
  • Mitochondria
  • Peroxisome
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point36.5 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility1000 mg/mL at 20 °CNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility240.0ALOGPS
logP-0.47ALOGPS
logP-0.0015ChemAxon
logS0.37ALOGPS
pKa (Strongest Acidic)4.02ChemAxon
pKa (Strongest Basic)-7.5ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area54.37 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity22.54 m3·mol-1ChemAxon
Polarizability9.16 Å3ChemAxon
Spectra
SpectraGC-MSMS/MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Mitochondria
  • Peroxisome
Biofluid Locations
  • Blood
  • Cellular Cytoplasm
  • Cerebrospinal Fluid (CSF)
  • Saliva
  • Urine
Tissue Location
  • Fibroblasts
  • Liver
  • Lymphocyte
  • Neuron
  • Spleen
Pathways
NameSMPDB LinkKEGG Link
Butyrate MetabolismSMP00073map00650
Fatty Acid BiosynthesisSMP00456Not Available
Ketone Body MetabolismSMP00071map00072
Phenylalanine and Tyrosine MetabolismSMP00008map00360
Tyrosine MetabolismSMP00006map00350
Valine, Leucine and Isoleucine DegradationSMP00032map00280
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified21.0 (0.0-86.0) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified40.6 +/- 36.5 uMAdult (>18 years old)Not SpecifiedNormal details
Cellular CytoplasmDetected and Quantified1700 (1500-1900) uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified26.2 +/- 12.3 uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
Cerebrospinal Fluid (CSF)Detected and Quantified12.0 +/- 14.0 uMNot SpecifiedBothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified6.0 +/- 6.0 uMAdult (>18 years old)Not SpecifiedNormal details
SalivaDetected and Quantified10.70 +/- 4.33 uMAdult (>18 years old)BothNormal
    • Dame, ZT. et al. ...
details
UrineDetected and Quantified0.15 (0.01-0.58) umol/mmol creatinineAdult (>18 years old)Male
Normal
details
UrineDetected and Quantified0.20 (0.020-0.82) umol/mmol creatinineAdult (>18 years old)Female
Normal
details
UrineDetected and Quantified11.1 (2.2-24.9) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified33.0(0.00-67.0) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified1.00 (0.00-2.00) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified27.3 +/- 14.4 uMAdult (>18 years old)Not SpecifiedHeart Transplant details
BloodDetected and Quantified3030.0 +/- 20.0 uMAdult (>18 years old)Both
Diabetes
details
Cellular CytoplasmDetected and Quantified1000 (800-1200) uMAdult (>18 years old)BothAnoxia details
Cerebrospinal Fluid (CSF)Detected and Quantified248 +/- 179 uMChildren (1-13 years old)Not SpecifiedGlucose transporter type 1 deficiency syndrome details
Cerebrospinal Fluid (CSF)Detected and Quantified322.0 (240.0-404.0) uMAdult (>18 years old)Both
Meningitis
details
UrineDetected and Quantified237.0 umol/mmol creatinineAdult (>18 years old)BothDiabetes details
UrineDetected and Quantified10025.00 (50.00-20000.00) umol/mmol creatinineChildren (1-13 years old)BothKetosis details
Associated Disorders and Diseases
Disease References
Anoxia
  1. Zupke C, Sinskey AJ, Stephanopoulos G: Intracellular flux analysis applied to the effect of dissolved oxygen on hybridomas. Appl Microbiol Biotechnol. 1995 Dec;44(1-2):27-36. Pubmed: 8579834
Diabetes mellitus type 2
  1. Tasker RC, Lutman D, Peters MJ: Hyperventilation in severe diabetic ketoacidosis. Pediatr Crit Care Med. 2005 Jul;6(4):405-11. Pubmed: 15982426
  2. Bales JR, Higham DP, Howe I, Nicholson JK, Sadler PJ: Use of high-resolution proton nuclear magnetic resonance spectroscopy for rapid multi-component analysis of urine. Clin Chem. 1984 Mar;30(3):426-32. Pubmed: 6321058
Glucose transporter type 1 deficiency syndrome
  1. Klepper J, Diefenbach S, Kohlschutter A, Voit T: Effects of the ketogenic diet in the glucose transporter 1 deficiency syndrome. Prostaglandins Leukot Essent Fatty Acids. 2004 Mar;70(3):321-7. Pubmed: 14769490
Ketosis
  1. MetaGene
Meningitis
  1. Subramanian A, Gupta A, Saxena S, Gupta A, Kumar R, Nigam A, Kumar R, Mandal SK, Roy R: Proton MR CSF analysis and a new software as predictors for the differentiation of meningitis in children. NMR Biomed. 2005 Jun;18(4):213-25. Pubmed: 15627241
Associated OMIM IDs
  • 606777 (Glucose transporter type 1 deficiency syndrome)
  • 125853 (Diabetes mellitus type 2)
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB021801
KNApSAcK IDNot Available
Chemspider ID94
KEGG Compound IDC00164
BioCyc ID3-KETOBUTYRATE
BiGG ID1485291
Wikipedia LinkAcetoacetic acid
NuGOwiki LinkHMDB00060
Metagene LinkHMDB00060
METLIN ID276
PubChem Compound96
PDB IDAAE
ChEBI ID15344
References
Synthesis ReferenceLopez-Soriano, F. J.; Argiles, J. M. A simple method for the preparation of acetoacetate. Analytical Letters (1985), 18(B5), 589-92.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Nicholson JK, Foxall PJ, Spraul M, Farrant RD, Lindon JC: 750 MHz 1H and 1H-13C NMR spectroscopy of human blood plasma. Anal Chem. 1995 Mar 1;67(5):793-811. Pubmed: 7762816
  2. 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
  3. Subramanian A, Gupta A, Saxena S, Gupta A, Kumar R, Nigam A, Kumar R, Mandal SK, Roy R: Proton MR CSF analysis and a new software as predictors for the differentiation of meningitis in children. NMR Biomed. 2005 Jun;18(4):213-25. Pubmed: 15627241
  4. Zupke C, Sinskey AJ, Stephanopoulos G: Intracellular flux analysis applied to the effect of dissolved oxygen on hybridomas. Appl Microbiol Biotechnol. 1995 Dec;44(1-2):27-36. Pubmed: 8579834
  5. Heller MJ, Adams PW, Orosz CG: Evaluation of an automated method of percent reactive antibody determination. Hum Immunol. 1992 Nov;35(3):179-87. Pubmed: 1293081
  6. Tasker RC, Lutman D, Peters MJ: Hyperventilation in severe diabetic ketoacidosis. Pediatr Crit Care Med. 2005 Jul;6(4):405-11. Pubmed: 15982426
  7. Oligny LL, Lough J: Hepatic sinusoidal ectasia. Hum Pathol. 1992 Aug;23(8):953-6. Pubmed: 1644440
  8. Nicholson JK, O'Flynn MP, Sadler PJ, Macleod AF, Juul SM, Sonksen PH: Proton-nuclear-magnetic-resonance studies of serum, plasma and urine from fasting normal and diabetic subjects. Biochem J. 1984 Jan 15;217(2):365-75. Pubmed: 6696735
  9. Galey JB, Destree O, Dumats J, Genard S, Tachon P: Protection against oxidative damage by iron chelators: effect of lipophilic analogues and prodrugs of N,N'-bis(3,4,5-trimethoxybenzyl)ethylenediamine- N,N'-diacetic acid (OR10141). J Med Chem. 2000 Apr 6;43(7):1418-21. Pubmed: 10753479
  10. Saibara T, Onishi S, Sone J, Yamamoto N, Shimahara Y, Mori K, Ozawa K, Yamamoto Y: Arterial ketone body ratio as a possible indicator for liver transplantation in fulminant hepatic failure. Transplantation. 1991 Apr;51(4):782-6. Pubmed: 2014530
  11. Mahowald ML, Handwerger BS, Capertone EM Jr, Douglas SD: A comparative study of procedures for sheep erythrocyte-human-T-lymphocyte rosette formation. J Immunol Methods. 1977;15(3):239-45. Pubmed: 404361
  12. Sato T, Oouchi M, Nagakubo H, Chiba T, Ogawa S, Sato C, Sugimura K, Fukuda M: Effect of pravastatin on plasma ketone bodies in diabetics with hypercholesterolemia. Tohoku J Exp Med. 1998 May;185(1):25-9. Pubmed: 9710942
  13. Krejsa CM, Schieven GL: Detection of oxidative stress in lymphocytes using dichlorodihydrofluorescein diacetate. Methods Mol Biol. 2000;99:35-47. Pubmed: 10909075
  14. Fritzsche I, Buhrdel P, Melcher R, Bohme HJ: Stability of ketone bodies in serum in dependence on storage time and storage temperature. Clin Lab. 2001;47(7-8):399-403. Pubmed: 11499803
  15. Polsky-Fisher SL, Cao H, Lu P, Gibson CR: Effect of cytochromes P450 chemical inhibitors and monoclonal antibodies on human liver microsomal esterase activity. Drug Metab Dispos. 2006 Aug;34(8):1361-6. Epub 2006 May 23. Pubmed: 16720683
  16. Fulop M, Murthy V, Michilli A, Nalamati J, Qian Q, Saitowitz A: Serum beta-hydroxybutyrate measurement in patients with uncontrolled diabetes mellitus. Arch Intern Med. 1999 Feb 22;159(4):381-4. Pubmed: 10030312
  17. Tanaka Y, Ohdan H, Onoe T, Mitsuta H, Tashiro H, Itamoto T, Asahara T: Low incidence of acute rejection after living-donor liver transplantation: immunologic analyses by mixed lymphocyte reaction using a carboxyfluorescein diacetate succinimidyl ester labeling technique. Transplantation. 2005 May 15;79(9):1262-7. Pubmed: 15880082
  18. Bales JR, Higham DP, Howe I, Nicholson JK, Sadler PJ: Use of high-resolution proton nuclear magnetic resonance spectroscopy for rapid multi-component analysis of urine. Clin Chem. 1984 Mar;30(3):426-32. Pubmed: 6321058
  19. de Araujo Burgos MG, Bion FM, Campos F: [Lactation and alcohol: clinical and nutritional effects] Arch Latinoam Nutr. 2004 Mar;54(1):25-35. Pubmed: 15332353
  20. Walker V, Mills GA, Mellor JM, Langley GJ, Farrant RD: A novel pyrroline-5-carboxylic acid and acetoacetic acid adduct in hyperprolinaemia type II. Clin Chim Acta. 2003 May;331(1-2):7-17. Pubmed: 12691858
  21. Yeh YY, Sheehan PM: Preferential utilization of ketone bodies in the brain and lung of newborn rats. Fed Proc. 1985 Apr;44(7):2352-8. Pubmed: 3884391

Enzymes

General function:
Involved in CoA-transferase activity
Specific function:
Key enzyme for ketone body catabolism. Transfers the CoA moiety from succinate to acetoacetate. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate.
Gene Name:
OXCT1
Uniprot ID:
P55809
Molecular weight:
56157.175
Reactions
Succinyl-CoA + Acetoacetic acid → Succinic acid + Acetoacetyl-CoAdetails
General function:
Involved in acetoacetate-CoA ligase activity
Specific function:
Activates acetoacetate to acetoacetyl-CoA. May be involved in utilizing ketone body for the fatty acid-synthesis during adipose tissue development (By similarity).
Gene Name:
AACS
Uniprot ID:
Q86V21
Molecular weight:
75143.645
Reactions
Adenosine triphosphate + Acetoacetic acid + Coenzyme A → Adenosine monophosphate + Pyrophosphate + Acetoacetyl-CoAdetails
General function:
Involved in oxidoreductase activity
Specific function:
Not Available
Gene Name:
ALDH2
Uniprot ID:
P05091
Molecular weight:
56380.93
General function:
Involved in catalytic activity
Specific function:
Key enzyme in ketogenesis (ketone body formation). Terminal step in leucine catabolism.
Gene Name:
HMGCL
Uniprot ID:
P35914
Molecular weight:
34359.84
Reactions
3-Hydroxy-3-methylglutaryl-CoA → Acetyl-CoA + Acetoacetic aciddetails
General function:
Involved in oxidoreductase activity
Specific function:
Dehydrogenase that mediates the formation of 2,5-dihydroxybenzoic acid (2,5-DHBA), a siderophore that shares structural similarities with bacterial enterobactin and associates with LCN2, thereby playing a key role in iron homeostasis and transport. Also acts as a 3-hydroxybutyrate dehydrogenase (By similarity).
Gene Name:
BDH2
Uniprot ID:
Q9BUT1
Molecular weight:
26723.57
Reactions
(R)-3-Hydroxybutyric acid + NAD → Acetoacetic acid + NADHdetails
(R)-3-Hydroxybutyric acid + NAD → Acetoacetic acid + NADH + Hydrogen Iondetails
General function:
Involved in fumarylacetoacetase activity
Specific function:
Not Available
Gene Name:
FAH
Uniprot ID:
P16930
Molecular weight:
46373.97
Reactions
4-Fumarylacetoacetic acid + Water → Acetoacetic acid + Fumaric aciddetails
Acetoacetic acid + Fumaric acid → 4-Fumarylacetoacetic acid + Waterdetails
General function:
Involved in oxidoreductase activity
Specific function:
Not Available
Gene Name:
BDH1
Uniprot ID:
Q02338
Molecular weight:
38156.77
Reactions
(R)-3-Hydroxybutyric acid + NAD → Acetoacetic acid + NADHdetails
(R)-3-Hydroxybutyric acid + NAD → Acetoacetic acid + NADH + Hydrogen Iondetails
General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the cofactor-independent reversible oxidation of gamma-hydroxybutyrate (GHB) to succinic semialdehyde (SSA) coupled to reduction of 2-ketoglutarate (2-KG) to D-2-hydroxyglutarate (D-2-HG). D,L-3-hydroxyisobutyrate and L-3-hydroxybutyrate (L-3-OHB) are also substrates for HOT with 10-fold lower activities.
Gene Name:
ADHFE1
Uniprot ID:
Q8IWW8
Molecular weight:
50307.42
Reactions
(S)-3-Hydroxybutyric acid + Oxoglutaric acid → Acetoacetic acid + D-2-Hydroxyglutaric aciddetails
General function:
Involved in CoA-transferase activity
Specific function:
Key enzyme for ketone body catabolism. Transfers the CoA moiety from succinate to acetoacetate. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate (By similarity).
Gene Name:
OXCT2
Uniprot ID:
Q9BYC2
Molecular weight:
56139.41
Reactions
Succinyl-CoA + Acetoacetic acid → Succinic acid + Acetoacetyl-CoAdetails
General function:
Involved in catalytic activity
Specific function:
Non-mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase that catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in ketogenesis, the products of which support energy production in nonhepatic animal tissues.
Gene Name:
HMGCLL1
Uniprot ID:
Q8TB92
Molecular weight:
36327.465
Reactions
3-Hydroxy-3-methylglutaryl-CoA → Acetyl-CoA + Acetoacetic aciddetails