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Record Information
Version2.0
Creation Date2014-08-29 06:51:31 UTC
Update Date2018-03-21 17:46:13 UTC
Accession NumberT3D4461
Identification
Common NameEthylmalonic acid
ClassSmall Molecule
DescriptionEthylmalonic acid, also known as alpha-carboxybutyric acid or ethylmalonate, is a member of the class of compounds known as branched fatty acids. Branched fatty acids are fatty acids containing one or more branched chains. Ethylmalonic acid is soluble (in water) and a moderately acidic compound (based on its pKa). Ethylmalonic acid can be synthesized from malonic acid, and can be synthesized into (S)-ethylmalonyl-CoA and (R)-ethylmalonyl-CoA. Ethylmalonic acid can be found in blood, cerebrospinal fluid (CSF), and urine, as well as in human fibroblasts, prostate, and skeletal muscle tissues. Moreover, ethylmalonic acid is found to be associated with anorexia nervosa and malonyl-CoA decarboxylase deficiency. Ethylmalonic acid is a non-carcinogenic (not listed by IARC) potentially toxic compound. Chronically high levels of ethylmalonic acid are associated with at least two inborn errors of metabolism, including short chain acyl CoA dehydrogenase deficiency (SCAD deficiency) and ethylmalonic encephalopathy. Ethylmalonic acid is identified in the urine of patients with short-chain acyl-coenzyme A dehydrogenase deficiency, which is a fatty acid metabolism disorder. When present in sufficiently high levels, ethylmalonic acid can act as an acidogen and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Ethylmalonic acid is an organic acid. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart abnormalities, kidney abnormalities, liver damage, seizures, coma, and possibly death. These are also the characteristic symptoms of the untreated IEMs mentioned above. Many affected children with organic acidemias experience intellectual disability or delayed development. In adults, acidosis or acidemia is characterized by headaches, confusion, feeling tired, tremors, sleepiness, and seizures.
Compound Type
  • Animal Toxin
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
Synonyms
Synonym
1,1-Propanedicarboxylate
1,1-Propanedicarboxylic acid
a-Carboxybutyrate
a-Carboxybutyric acid
alpha-Carboxybutyrate
alpha-Carboxybutyric acid
Ethyl-Malonic acid
Ethylmalonate
Chemical FormulaC5H8O4
Average Molecular Mass132.115 g/mol
Monoisotopic Mass132.042 g/mol
CAS Registry Number601-75-2
IUPAC Name2-ethylpropanedioic acid
Traditional Nameethylmalonic acid
SMILESCCC(C(O)=O)C(O)=O
InChI IdentifierInChI=1S/C5H8O4/c1-2-3(4(6)7)5(8)9/h3H,2H2,1H3,(H,6,7)(H,8,9)
InChI KeyInChIKey=UKFXDFUAPNAMPJ-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as branched fatty acids. These are fatty acids containing a branched chain.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty acids and conjugates
Direct ParentBranched fatty acids
Alternative Parents
Substituents
  • Branched fatty acid
  • 1,3-dicarbonyl compound
  • Dicarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Fibroblasts
  • Prostate
  • Skeletal Muscle
Pathways
NameSMPDB LinkKEGG Link
Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency)SMP00235 Not Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point112 - 114°C
Boiling PointNot Available
Solubility712.0 mg/mL
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility94.1 g/LALOGPS
logP0.43ALOGPS
logP0.66ChemAxon
logS-0.15ALOGPS
pKa (Strongest Acidic)2.5ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.6 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity28.16 m³·mol⁻¹ChemAxon
Polarizability11.98 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-0002-0910000000-ff684346010454e439ecJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0gvx-9100000000-9713da0bdd2cd0b28ebaJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0002-0920000000-c6908d036ed13e7ba519JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0002-0910000000-ff684346010454e439ecJSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-004u-9400000000-c51992693b05221f3a8aJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00dr-9220000000-10ce85512076eaa6afdeJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Negative (Annotated)splash10-000l-9000000000-ed08eca90f357944aee9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Negative (Annotated)splash10-0006-9000000000-b6e83c7aef56876fa1b3JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Negative (Annotated)splash10-0006-9000000000-409423c1bfecc553b24eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , negativesplash10-000i-9000000000-d15979561ae10b3c94dfJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 10V, Negativesplash10-000i-9000000000-6cd825b16df28e77024aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 20V, Negativesplash10-00kr-9000000000-32cc5c19f1f63ea75c17JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 40V, Negativesplash10-0gb9-9000000000-c8fadac6a17104d7abf6JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 35V, Negativesplash10-000i-9000000000-e7765d86ee8d74f0f9d6JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 35V, Negativesplash10-000i-9000000000-4086dd4566bac56688a9JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00lr-3900000000-7ad5e5da82f0646b39dbJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-9600000000-00a7e2649b402719b2faJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00kf-9000000000-6cd3362f5cdb53773ce8JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0019-9400000000-257e80506d0172d05d98JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000l-9000000000-e79d02ff9ead3516adaaJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-c55403c45b1243b9628eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00ku-9100000000-bf24e61d0219e165c8deJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-9000000000-f4c23282a114d4982d2dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-5a0f73206eec5978645dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-9300000000-fec5eeeb4f241984f787JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014r-9000000000-08c6ded2366ed022deabJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014i-9000000000-76b92022e3a050e0fb1eJSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0udr-9300000000-e531a154ddaf695ebe5bJSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityEthylmalonic acid is identified in the urine of patients with short-chain acyl-coenzyme A dehydrogenase deficiency, which is a fatty acid metabolism disorder.
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesThis is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.
Minimum Risk LevelNot Available
Health EffectsChronically high levels of ethylmalonic acid are associated with at least 2 inborn errors of metabolism including: Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency) and Ethylmalonic Encephalopathy.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB00622
PubChem Compound ID11756
ChEMBL IDCHEMBL1160009
ChemSpider ID11263
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID741548
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceZakharova, T. V.; Ternovaya, T. V.; Pirkes, S. B.; Kostromina, N. A. Study of complexing in the neodymium-ethylmalonic acid system by a spectrographic method. Zhurnal Neorganicheskoi Khimii (1979), 24(7), 1827-31.
MSDSLink
General References
  1. Tiranti V, D'Adamo P, Briem E, Ferrari G, Mineri R, Lamantea E, Mandel H, Balestri P, Garcia-Silva MT, Vollmer B, Rinaldo P, Hahn SH, Leonard J, Rahman S, Dionisi-Vici C, Garavaglia B, Gasparini P, Zeviani M: Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein. Am J Hum Genet. 2004 Feb;74(2):239-52. Epub 2004 Jan 19. [14732903 ]
  2. McGowan KA, Nyhan WL, Barshop BA, Naviaux RK, Yu A, Haas RH, Townsend JJ: The role of methionine in ethylmalonic encephalopathy with petechiae. Arch Neurol. 2004 Apr;61(4):570-4. [15096407 ]
  3. Guneral F, Bachmann C: Age-related reference values for urinary organic acids in a healthy Turkish pediatric population. Clin Chem. 1994 Jun;40(6):862-6. [8087979 ]
  4. Birkebaek NH, Simonsen H, Gregersen N: Hypoglycaemia and elevated urine ethylmalonic acid in a child homozygous for the short-chain acyl-CoA dehydrogenase 625G > A gene variation. Acta Paediatr. 2002;91(4):480-2. [12061367 ]
  5. Tanaka K, Ramsdell HS, Baretz BH, Keefe MB, Kean EA, Johnson B: Identification of ethylmalonic acid in urine of two patients with the vomitting sickness of Jamaica. Clin Chim Acta. 1976 May 17;69(1):105-12. [1269146 ]
  6. Bhala A, Willi SM, Rinaldo P, Bennett MJ, Schmidt-Sommerfeld E, Hale DE: Clinical and biochemical characterization of short-chain acyl-coenzyme A dehydrogenase deficiency. J Pediatr. 1995 Jun;126(6):910-5. [7776094 ]
  7. Bok LA, Vreken P, Wijburg FA, Wanders RJ, Gregersen N, Corydon MJ, Waterham HR, Duran M: Short-chain Acyl-CoA dehydrogenase deficiency: studies in a large family adding to the complexity of the disorder. Pediatrics. 2003 Nov;112(5):1152-5. [14595061 ]
  8. Barschak AG, Ferreira Gda C, Andre KR, Schuck PF, Viegas CM, Tonin A, Dutra Filho CS, Wyse AT, Wannmacher CM, Vargas CR, Wajner M: Inhibition of the electron transport chain and creatine kinase activity by ethylmalonic acid in human skeletal muscle. Metab Brain Dis. 2006 Mar;21(1):11-9. Epub 2006 Apr 28. [16773466 ]
  9. 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. doi: 10.1038/nature07762. [19212411 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Nad+ binding
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:
34293.275 Da