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Human Metabolome Database Version 3.5

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Showing metabocard for Acetoacetic acid (HMDB00060)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-02-08 17:07:50 -0700
HMDB ID HMDB00060
Secondary Accession Numbers None
Metabolite Identification
Common Name Acetoacetic acid
Description It 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 Link_out) 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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
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 Formula C4H6O3
Average Molecular Weight 102.0886
Monoisotopic Molecular Weight 102.031694058
IUPAC Name 3-oxobutanoic acid
Traditional IUPAC Name acetoacetic acid
CAS Registry Number 541-50-4
SMILES CC(=O)CC(O)=O
InChI Identifier InChI=1S/C4H6O3/c1-3(5)2-4(6)7/h2H2,1H3,(H,6,7)
InChI Key WDJHALXBUFZDSR-UHFFFAOYSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Organic Acids and Derivatives
Class Keto-Acids and Derivatives
Sub Class Beta 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 Parent Beta Keto-Acids and Derivatives
Ontology
Status Detected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Butanoate metabolism
  • Component of Tyrosine metabolism
Application Not Available
Cellular locations
  • Cytoplasm
  • Extracellular
  • Mitochondria
  • Peroxisome
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point 36.5 °C Not Available
Boiling Point Not Available Not Available
Water Solubility 1000 mg/mL at 20 °C Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
Water Solubility 240 g/L ALOGPS
LogP -0.47 ALOGPS
LogP -0.0015 ChemAxon
LogS 0.37 ALOGPS
pKa (strongest acidic) 4.02 ChemAxon
pKa (strongest basic) -7.5 ChemAxon
Hydrogen Acceptor Count 3 ChemAxon
Hydrogen Donor Count 1 ChemAxon
Polar Surface Area 54.37 A2 ChemAxon
Rotatable Bond Count 2 ChemAxon
Refractivity 22.54 ChemAxon
Polarizability 9.16 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge -1 ChemAxon
Spectra
Gas-MS Spectrum
1H NMR Spectrum
13C NMR Spectrum
MS/MS Spectrum Quattro_QQQ 10
MS/MS Spectrum Quattro_QQQ 25
MS/MS Spectrum Quattro_QQQ 40
MS/MS Spectrum GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies )
MS/MS Spectrum GC-MS
MS/MS Spectrum GC-MS
MS/MS Spectrum GC-MS
MS/MS Spectrum GC-MS
[1H,13C] 2D NMR Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Mitochondria
  • Peroxisome
Biofluid Locations
  • Blood
  • Cellular Cytoplasm
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Fibroblasts
  • Lymphocyte
  • Neuron
  • Liver
  • Spleen
Pathways
Name SMPDB Link KEGG Link
Ketone Body Metabolism SMP00071 map00072 Link_out
Tyrosine Metabolism SMP00006 map00350 Link_out
Butyrate Metabolism SMP00073 map00650 Link_out
Valine, Leucine and Isoleucine Degradation SMP00032 map00280 Link_out
Phenylalanine and Tyrosine Metabolism SMP00008 map00360 Link_out
Fatty Acid Biosynthesis SMP00456 Not Available
Normal Concentrations
Biofluid Status Value Age Sex Condition Comments
Blood Detected and Quantified
Article_icon
21.0 (0.0-86.0) uM Adult (>18 years old) Both Normal Not Available
Blood Detected and Quantified
Article_icon
40.6 +/- 36.5 uM Adult (>18 years old) Not Specified Normal Not Available
Cellular Cytoplasm Detected and Quantified
Article_icon
1700 (1500-1900) uM Adult (>18 years old) Both Normal Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
Article_icon
26.2 +/- 12.3 uM Adult (>18 years old) Both Normal Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
Article_icon
12.0 +/- 14.0 uM Not Specified Both Normal Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
Article_icon
6.0 +/- 6.0 uM Adult (>18 years old) Not Specified Normal Not Available
Urine Detected and Quantified
Article_icon
0.15 (0.01-0.58) umol/mmol creatinine Adult (>18 years old) Male Normal Not Available
Urine Detected and Quantified
Article_icon
0.20 (0.020-0.82) umol/mmol creatinine Adult (>18 years old) Female Normal Not Available
Urine Detected and Quantified
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11.1 (2.2-24.9) umol/mmol creatinine Adult (>18 years old) Both Normal urine by NMR
Urine Detected and Quantified
Article_icon
33.0(0.00-67.0) umol/mmol creatinine Adult (>18 years old) Both Normal Not Available
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Comments
Blood Detected and Quantified
Article_icon
27.3 +/- 14.4 uM Adult (>18 years old) Not Specified Heart Transplant Not Available
Blood Detected and Quantified
Article_icon
3030.0 +/- 20.0 uM Adult (>18 years old) Both Diabetes With ketoacidosis
Cellular Cytoplasm Detected and Quantified
Article_icon
1000 (800-1200) uM Adult (>18 years old) Both Anoxia Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
Article_icon
248 +/- 179 uM Children (1-13 year old) Not Specified Glucose transporter type 1 deficiency syndrome Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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322.0 (240.0-404.0) uM Adult (>18 years old) Both Meningitis Bacterial
Urine Detected and Quantified
Article_icon
237.0 umol/mmol creatinine Adult (>18 years old) Both Diabetes Not Available
Urine Detected and Quantified
Article_icon
1.00 (0.00-2.00) umol/mmol creatinine Adult (>18 years old) Both Ketosis Not Available
Urine Detected and Quantified
Article_icon
10025.00 (50.00-20000.00) umol/mmol creatinine Adult (>18 years old) Both Ketosis Not Available
Associated Disorders and Diseases
Disease References
Glucose transporter type 1 deficiency syndrome
  • 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 Link_out
    Anoxia
    • 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 Link_out
      Diabetes mellitus type 2
      • Tasker RC, Lutman D, Peters MJ: Hyperventilation in severe diabetic ketoacidosis. Pediatr Crit Care Med. 2005 Jul;6(4):405-11. Pubmed: 15982426 Link_out
      • 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 Link_out
        Meningitis
        • 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 Link_out
          Ketosis
            • http://www.metagene.de/program/d.prg?mp=KETOSIS,%20UNSPECIFIC%20[DD]
            Associated OMIM IDs
            • 125853 Link_out (Diabetes mellitus type 2)
            • 606777 Link_out (Glucose transporter type 1 deficiency syndrome)
            DrugBank ID Not Available
            Phenol Explorer Compound ID Not Available
            Phenol Explorer Metabolite ID Not Available
            FoodDB ID FDB021801
            KNApSAcK ID Not Available
            Chemspider ID 94 Link_out
            KEGG Compound ID C00164 Link_out
            BioCyc ID 3-KETOBUTYRATE Link_out
            BiGG ID 1485291 Link_out
            Wikipedia Link Acetoacetic acid Link_out
            NuGOwiki Link HMDB00060 Link_out
            Metagene Link HMDB00060 Link_out
            METLIN ID 276 Link_out
            PubChem Compound 96 Link_out
            PDB ID AAE Link_out
            ChEBI ID 15344 Link_out
            References
            Synthesis Reference Lopez-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. 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 Link_out
            2. 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 Link_out
            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 Link_out
            4. Tasker RC, Lutman D, Peters MJ: Hyperventilation in severe diabetic ketoacidosis. Pediatr Crit Care Med. 2005 Jul;6(4):405-11. Pubmed: 15982426 Link_out
            5. Oligny LL, Lough J: Hepatic sinusoidal ectasia. Hum Pathol. 1992 Aug;23(8):953-6. Pubmed: 1644440 Link_out
            6. 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 Link_out
            7. 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 Link_out
            8. 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 Link_out
            9. 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 Link_out
            10. 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 Link_out
            11. 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 Link_out
            12. 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 Link_out
            13. Krejsa CM, Schieven GL: Detection of oxidative stress in lymphocytes using dichlorodihydrofluorescein diacetate. Methods Mol Biol. 2000;99:35-47. Pubmed: 10909075 Link_out
            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 Link_out
            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 Link_out
            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 Link_out
            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 Link_out
            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 Link_out
            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 Link_out
            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 Link_out
            Enzymes
            Name: Hydroxymethylglutaryl-CoA lyase, mitochondrial
            Reactions:
            • (S)-3-hydroxy-3-methylglutaryl-CoA = acetyl-CoA + acetoacetate [RN:R01360]
            Gene Name: HMGCL
            Uniprot ID: P35914 Link_out
            Protein Sequence: FASTA
            Gene Sequence: FASTA
            Name: Aldehyde dehydrogenase, mitochondrial
            Reactions:
            • an aldehyde + NAD+ + H2O = an acid + NADH + H+ [RN:R00538]
            Gene Name: ALDH2
            Uniprot ID: P05091 Link_out
            Protein Sequence: FASTA
            Gene Sequence: FASTA
            Name: D-beta-hydroxybutyrate dehydrogenase, mitochondrial
            Reactions:
            • (R)-3-hydroxybutanoate + NAD+ = acetoacetate + NADH + H+ [RN:R01361]
            Gene Name: BDH1
            Uniprot ID: Q02338 Link_out
            Protein Sequence: FASTA
            Gene Sequence: FASTA
            Name: Succinyl-CoA:3-ketoacid-coenzyme A transferase 1, mitochondrial
            Reactions:
            • succinyl-CoA + a 3-oxo acid = succinate + a 3-oxoacyl-CoA [RN:R01780]
            Gene Name: OXCT1
            Uniprot ID: P55809 Link_out
            Protein Sequence: FASTA
            Gene Sequence: FASTA
            Name: Fumarylacetoacetase
            Reactions:
            • 4-fumarylacetoacetate + H2O = acetoacetate + fumarate [RN:R01364]
            Gene Name: FAH
            Uniprot ID: P16930 Link_out
            Protein Sequence: FASTA
            Gene Sequence: FASTA
            Name: Succinyl-CoA:3-ketoacid-coenzyme A transferase 2, mitochondrial
            Reactions:
            • succinyl-CoA + a 3-oxo acid = succinate + a 3-oxoacyl-CoA [RN:R01780]
            Gene Name: OXCT2
            Uniprot ID: Q9BYC2 Link_out
            Protein Sequence: FASTA
            Gene Sequence: FASTA
            Name: Hydroxyacid-oxoacid transhydrogenase, mitochondrial
            Reactions:
            • (S)-3-hydroxybutanoate + 2-oxoglutarate = acetoacetate + (R)-2-hydroxyglutarate [RN:R03225]
            Gene Name: ADHFE1
            Uniprot ID: Q8IWW8 Link_out
            Protein Sequence: FASTA
            Gene Sequence: FASTA
            Name: Acetoacetyl-CoA synthetase
            Reactions:
            • ATP + acetoacetate + CoA = AMP + diphosphate + acetoacetyl-CoA [RN:R01357]
            Gene Name: AACS
            Uniprot ID: Q86V21 Link_out
            Protein Sequence: FASTA
            Gene Sequence: FASTA
            Name: Probable 3-hydroxymethyl-3-methylglutaryl-CoA lyase 2
            Reactions:
            • (S)-3-hydroxy-3-methylglutaryl-CoA = acetyl-CoA + acetoacetate [RN:R01360]
            Gene Name: HMGCLL1
            Uniprot ID: Q8TB92 Link_out
            Protein Sequence: FASTA
            Gene Sequence: FASTA
            Name: 3-hydroxybutyrate dehydrogenase type 2
            Reactions:
            • (R)-3-hydroxybutanoate + NAD+ = acetoacetate + NADH + H+ [RN:R01361]
            Gene Name: BDH2
            Uniprot ID: Q9BUT1 Link_out
            Protein Sequence: FASTA
            Gene Sequence: FASTA