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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2006-02-02 11:25:17 UTC
Update Date2020-11-09 23:15:54 UTC
HMDB IDHMDB0001844
Secondary Accession Numbers
  • HMDB01844
Metabolite Identification
Common NameMethylsuccinic acid
DescriptionMethylsuccinic acid (CAS: 498-21-5) is a normal metabolite found in human fluids. Increased urinary levels of methylsuccinic acid (together with ethylmalonic acid) are the main biochemical measurable features in ethylmalonic encephalopathy (OMIM: 602473 ), a rare metabolic disorder with an autosomal recessive mode of inheritance that is clinically characterized by neuromotor delay, hyperlactic acidemia, recurrent petechiae, orthostatic acrocyanosis, and chronic diarrhea (PMID: 12382164 ). The underlying biochemical defect involves isoleucine catabolism (PMID: 9667231 ). Methylsuccinic acid levels were found to have decreased in the urine of animals under D-serine-induced nephrotoxicity (D-serine causes selective necrosis of the proximal straight tubules in the rat kidney) (PMID: 15596249 ). Moreover, methylsuccinic acid is found to be associated with ethylmalonic encephalopathy, isovaleric acidemia, and medium-chain acyl-CoA dehydrogenase deficiency, which are also inborn errors of metabolism.
Structure
Data?1584460566
Synonyms
ValueSource
(S)-2-Methylbutanedioic acidChEBI
(S)-2-MethylbutanedioateGenerator
(S)-MethylsuccinateGenerator
(-)-(2S)-Methylbutanedioic acidHMDB
(-)-(S)-alpha-Methylsuccinic acidHMDB
(-)-(S)-α-Methylsuccinic acidHMDB
(-)-2-Methylsuccinic acidHMDB
(-)-Methylsuccinic acidHMDB
(-)-alpha-Methylsuccinic acidHMDB
(-)-α-Methylsuccinic acidHMDB
(2S)-2-Methylbutanedioic acidHMDB
(2S)-Methylbutanedioic acidHMDB
(S)-(-)-2-Methylsuccinic acidHMDB
(S)-(-)-Methylsuccinic acidHMDB
(S)-2-Methylsuccinic acidHMDB
(S)-Methylsuccinic acidHMDB
(S)-alpha-Methylsuccinic acidHMDB
(S)-α-Methylsuccinic acidHMDB
1,2-Propanedicarboxylic acidHMDB
2-Methylbutane-1,4-dioic acidHMDB
2-Methylbutanedioic acidHMDB
2-Methylsuccinic acidHMDB
Methylbutanedioic acidHMDB
Methylsuccinic acidHMDB
Pyrotartaric acidHMDB
alpha-Methylsuccinic acidHMDB
α-Methylsuccinic acidHMDB
Chemical FormulaC5H8O4
Average Molecular Weight132.115
Monoisotopic Molecular Weight132.042258738
IUPAC Name(2S)-2-methylbutanedioic acid
Traditional Name(2S)-2-methylbutanedioic acid
CAS Registry Number2174-58-5
SMILES
C[C@@H](CC(O)=O)C(O)=O
InChI Identifier
InChI=1S/C5H8O4/c1-3(5(8)9)2-4(6)7/h3H,2H2,1H3,(H,6,7)(H,8,9)/t3-/m0/s1
InChI KeyWXUAQHNMJWJLTG-VKHMYHEASA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as methyl-branched fatty acids. These are fatty acids with an acyl chain that has a methyl branch. Usually, they are saturated and contain only one or more methyl group. However, branches other than methyl may be present.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty acids and conjugates
Direct ParentMethyl-branched fatty acids
Alternative Parents
Substituents
  • Methyl-branched fatty acid
  • 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 DescriptorsNot Available
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point117.5 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility516.5 mg/mLHuman Metabolome Project
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility103 g/LALOGPS
logP0.13ALOGPS
logP0.14ChemAxon
logS-0.11ALOGPS
pKa (Strongest Acidic)3.99ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.6 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity28.11 m³·mol⁻¹ChemAxon
Polarizability11.87 ųChemAxon
Number of Rings0ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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-b99795b0e5069d573c2dSpectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0002-0920000000-c96774045667ea1804dfSpectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0002-0910000000-b99795b0e5069d573c2dSpectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-014i-3900000000-4afd6f9cd1309a7a392bSpectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-00kr-9600000000-e212a368f465b41cc1faSpectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0l0i-9200000000-c712b36382fde51f3ae5Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-000i-9400000000-f709b1c905420a006038Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) 30V, Negativesplash10-0019-9400000000-40a1055d8102e323a077Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-000i-9400000000-f709b1c905420a006038Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-0019-9400000000-40a1055d8102e323a077Spectrum
MSMass Spectrum (Electron Ionization)splash10-0077-9000000000-1bd08b69cec7f9966cb2Spectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR1H NMR SpectrumNot AvailableSpectrum
1D NMR13C NMR SpectrumNot AvailableSpectrum
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableSpectrum
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biospecimen Locations
  • Blood
  • Feces
  • Saliva
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot Available
Normal
      Not Available
details
BloodDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Not Specified
Normal
details
FecesDetected but not QuantifiedNot QuantifiedNot SpecifiedNot Specified
Normal
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
FecesDetected and Quantified81.520 +/- 46.853 nmol/g wet fecesNot SpecifiedNot Specified
Normal
details
FecesDetected and Quantified151.384 +/- 209.666 nmol/g wet fecesNot SpecifiedNot Specified
Normal
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot QuantifiedNot SpecifiedNot Specified
Normal
details
SalivaDetected and Quantified8.04 +/- 0.4 uMAdult (>18 years old)BothNormal
    • Zerihun T. Dame, ...
details
UrineDetected and Quantified<3.392 umol/mmol creatinineNewborn (0-30 days old)FemaleNormal details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)MaleNormal details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
UrineDetected and Quantified1.56 +/- 1.12 umol/mmol creatinineAdult (>18 years old)BothNot Available details
UrineDetected and Quantified4.899 +/- 3.586 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected and Quantified5.06 +/- 0.99 umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected and Quantified0.69-1.2 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified2.3 (0.8-10.8) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified<2.0 umol/mmol creatinineChildren (1-13 years old)MaleNormal details
UrineDetected and Quantified<3.392 umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified2-3 umol/mmol creatinineChildren (1 - 13 years old)BothNormal details
UrineDetected and Quantified5 +/- 3 umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified2.7 umol/mmol creatinineNewborn (0-30 days old)BothNormal details
UrineDetected and Quantified4.8 umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified2.8 umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected and Quantified2.6 umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected and Quantified2 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified<3.89 umol/mmol creatinineChildren (1 - 18 years old)Both
Normal
    • BC Children's Hos...
details
UrineDetected and Quantified0.900 +/- 0.800 umol/mmol creatinineAdult (>18 years old)Not SpecifiedNormal
    • Geigy Scientific ...
details
UrineDetected and Quantified1.900 +/- 0.700 umol/mmol creatinineChildren (1 - 13 years old)Not SpecifiedNormal
    • Geigy Scientific ...
details
UrineDetected and Quantified0-1.9 umol/mmol creatinineInfant (0-1 year old)Male
Normal
details
UrineDetected and Quantified0-3.0 umol/mmol creatinineInfant (0-1 year old)Male
Normal
details
UrineDetected and Quantified0-3.1 umol/mmol creatinineInfant (0-1 year old)Female
Normal
details
UrineDetected and Quantified0-5.3 umol/mmol creatinineInfant (0-1 year old)Female
Normal
details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
UrineDetected and Quantified0.53-0.85 umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified4.7 (1.1-6.2) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified3.2 (0.7-9.9) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified1.065 +/- 0.863 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Irritable bowel syndrome
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Ulcerative colitis
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothColorectal Cancer details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Colorectal cancer
details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Colorectal cancer
details
UrineDetected and Quantified22.612-101.754 umol/mmol creatinineNewborn (0-30 days old)FemaleShort Chain Acyl-Coa Dehydrogenase Deficiency details
UrineDetected and Quantified6.467 +/- 5.597 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified2.81 +/- 0.57 umol/mmol creatinineChildren (1-13 years old)BothMalnutrition (type kwashiorkor and marasmus) details
UrineDetected and Quantified1.9 (1.3-2.5) umol/mmol creatinineAdult (>18 years old)BothRefsum's disease details
UrineDetected and Quantified7.2 umol/mmol creatinineChildren (1-13 years old)MaleEthylmalonic encephalopathy details
UrineDetected and Quantified0.900-16.700 umol/mmol creatinineInfant (0-1 year old)Not Specified
isovaleric acidemia
details
UrineDetected and Quantified1.100-5.900 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
isovaleric acidemia
details
UrineDetected and Quantified11.400-17.300 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
isovaleric acidemia
details
UrineDetected and Quantified22.612-101.754 umol/mmol creatinineInfant (0-1 year old)Female
Short chain acyl-CoA dehydrogenase deficiency (SCAD)
details
UrineDetected and Quantified3-9 umol/mmol creatinineChildren (1 - 13 years old)BothMedium Chain Acyl-CoA Dehydrogenase Deficiency details
UrineDetected and Quantified5.200-62.500 umol/mmol creatinineInfant (0-1 year old)Not Specified
isovaleric acidemia
details
UrineDetected and Quantified6-630 umol/mmol creatinineInfant (0-1 year old)Both
Short chain acyl-CoA Dehydrogenase deficiency (SCAD)
details
UrineDetected and Quantified25.309 +/- 83.321 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified1.628 +/- 1.644 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Gastroesophageal reflux disease
    • Mordechai, Hien, ...
details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothBladder cancer details
Associated Disorders and Diseases
Disease References
Irritable bowel syndrome
  1. Le Gall G, Noor SO, Ridgway K, Scovell L, Jamieson C, Johnson IT, Colquhoun IJ, Kemsley EK, Narbad A: Metabolomics of fecal extracts detects altered metabolic activity of gut microbiota in ulcerative colitis and irritable bowel syndrome. J Proteome Res. 2011 Sep 2;10(9):4208-18. doi: 10.1021/pr2003598. Epub 2011 Aug 8. [PubMed:21761941 ]
Ulcerative colitis
  1. Le Gall G, Noor SO, Ridgway K, Scovell L, Jamieson C, Johnson IT, Colquhoun IJ, Kemsley EK, Narbad A: Metabolomics of fecal extracts detects altered metabolic activity of gut microbiota in ulcerative colitis and irritable bowel syndrome. J Proteome Res. 2011 Sep 2;10(9):4208-18. doi: 10.1021/pr2003598. Epub 2011 Aug 8. [PubMed:21761941 ]
Colorectal cancer
  1. Brown DG, Rao S, Weir TL, O'Malia J, Bazan M, Brown RJ, Ryan EP: Metabolomics and metabolic pathway networks from human colorectal cancers, adjacent mucosa, and stool. Cancer Metab. 2016 Jun 6;4:11. doi: 10.1186/s40170-016-0151-y. eCollection 2016. [PubMed:27275383 ]
  2. Sinha R, Ahn J, Sampson JN, Shi J, Yu G, Xiong X, Hayes RB, Goedert JJ: Fecal Microbiota, Fecal Metabolome, and Colorectal Cancer Interrelations. PLoS One. 2016 Mar 25;11(3):e0152126. doi: 10.1371/journal.pone.0152126. eCollection 2016. [PubMed:27015276 ]
  3. Goedert JJ, Sampson JN, Moore SC, Xiao Q, Xiong X, Hayes RB, Ahn J, Shi J, Sinha R: Fecal metabolomics: assay performance and association with colorectal cancer. Carcinogenesis. 2014 Sep;35(9):2089-96. doi: 10.1093/carcin/bgu131. Epub 2014 Jul 18. [PubMed:25037050 ]
Refsum's disease
  1. Greter J, Lindstedt S, Steen G: 2,6-Dimethyloctanedioic acid--a metabolite of phytanic acid in Refsum's disease. Clin Chem. 1983 Mar;29(3):434-7. [PubMed:6186413 ]
Eosinophilic esophagitis
  1. (). Mordechai, Hien, and David S. Wishart. .
Ethylmalonic encephalopathy
  1. Di Rocco M, Caruso U, Briem E, Rossi A, Allegri AE, Buzzi D, Tiranti V: A case of ethylmalonic encephalopathy with atypical clinical and biochemical presentation. Mol Genet Metab. 2006 Dec;89(4):395-7. Epub 2006 Jul 7. [PubMed:16828325 ]
Isovaleric acidemia
  1. Loots DT: Abnormal tricarboxylic acid cycle metabolites in isovaleric acidaemia. J Inherit Metab Dis. 2009 Jun;32(3):403-11. doi: 10.1007/s10545-009-1071-6. Epub 2009 Apr 5. [PubMed:19343532 ]
Short Chain Acyl-Coa Dehydrogenase Deficiency
  1. Amendt BA, Greene C, Sweetman L, Cloherty J, Shih V, Moon A, Teel L, Rhead WJ: Short-chain acyl-coenzyme A dehydrogenase deficiency. Clinical and biochemical studies in two patients. J Clin Invest. 1987 May;79(5):1303-9. [PubMed:3571488 ]
  2. 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. [PubMed:7776094 ]
Medium Chain Acyl-CoA Dehydrogenase Deficiency
  1. Gregersen N, Kolvraa S, Rasmussen K, Mortensen PB, Divry P, David M, Hobolth N: General (medium-chain) acyl-CoA dehydrogenase deficiency (non-ketotic dicarboxylic aciduria): quantitative urinary excretion pattern of 23 biologically significant organic acids in three cases. Clin Chim Acta. 1983 Aug 15;132(2):181-91. [PubMed:6616873 ]
Associated OMIM IDs
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB022704
KNApSAcK IDNot Available
Chemspider ID5323413
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia Link2-Methylsuccinic acid
METLIN IDNot Available
PubChem Compound6950476
PDB IDNot Available
ChEBI ID91316
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDMDB00000343
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. 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. [PubMed:8087979 ]
  2. 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. [PubMed:7776094 ]
  3. Grosso S, Mostardini R, Farnetani MA, Molinelli M, Berardi R, Dionisi-Vici C, Rizzo C, Morgese G, Balestri P: Ethylmalonic encephalopathy: further clinical and neuroradiological characterization. J Neurol. 2002 Oct;249(10):1446-50. [PubMed:12382164 ]
  4. Nowaczyk MJ, Lehotay DC, Platt BA, Fisher L, Tan R, Phillips H, Clarke JT: Ethylmalonic and methylsuccinic aciduria in ethylmalonic encephalopathy arise from abnormal isoleucine metabolism. Metabolism. 1998 Jul;47(7):836-9. [PubMed:9667231 ]
  5. Williams RE, Major H, Lock EA, Lenz EM, Wilson ID: D-Serine-induced nephrotoxicity: a HPLC-TOF/MS-based metabonomics approach. Toxicology. 2005 Feb 14;207(2):179-90. [PubMed:15596249 ]