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Record Information
Version3.6
Creation Date2006-02-02 11:25:17 UTC
Update Date2016-06-10 21:22:57 UTC
HMDB IDHMDB01844
Secondary Accession NumbersNone
Metabolite Identification
Common NameMethylsuccinic acid
DescriptionMethylsuccinic acid 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 ) T he underlying biochemical defect involves isoleucine catabolism. (PMID 9667231 ). It has been found decreases 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 ).
Structure
Thumb
Synonyms
ValueSource
(S)-2-Hydroxy-2-methylsuccinateHMDB
(S)-2-Hydroxy-2-methylsuccinic acidHMDB
(S)-CitramalateHMDB
(S)-Citramalic acidHMDB
2-MethylbutanedioateHMDB
2-MethylsuccinateHMDB
2-Methylsuccinic acidHMDB
Methyl succinateHMDB
Methyl succinic acidHMDB
MethylbutanedioateHMDB
Methylbutanedioic acidHMDB
MethylsuccinateHMDB
MEZHMDB
PyrotartarateHMDB
Pyrotartaric acidHMDB
Chemical FormulaC5H8O4
Average Molecular Weight132.1146
Monoisotopic Molecular Weight132.042258744
IUPAC Name2-methylbutanedioic acid
Traditional Namemethylsuccinic acid
CAS Registry Number498-21-5
SMILES
CC(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)
InChI KeyInChIKey=WXUAQHNMJWJLTG-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound 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
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External DescriptorsNot Available
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
BiofunctionNot Available
ApplicationNot Available
Cellular locations
  • Cytoplasm (predicted from logP)
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 Solubility103.0 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity28.11 m3·mol-1ChemAxon
Polarizability11.91 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)splash10-0002-0910000000-b99795b0e5069d573c2dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-014i-3900000000-4afd6f9cd1309a7a392bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-00kr-9600000000-e212a368f465b41cc1faView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0l0i-9200000000-c712b36382fde51f3ae5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-000i-9400000000-f709b1c905420a006038View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) 30V, Negativesplash10-0019-9400000000-40a1055d8102e323a077View in MoNA
MSMass Spectrum (Electron Ionization)splash10-0077-9000000000-1bd08b69cec7f9966cb2View in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid Locations
  • Blood
  • Feces
  • Saliva
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot Available
Normal
  • Not Applicable
details
FecesDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
FecesDetected but not QuantifiedNot ApplicableNot SpecifiedNot Specified
Normal
details
FecesDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
FecesDetected and Quantified81.520 +/- 46.853 uMNot SpecifiedNot Specified
Normal
details
FecesDetected and Quantified151.384 +/- 209.666 uMNot SpecifiedNot Specified
Normal
details
FecesDetected but not QuantifiedNot ApplicableNot SpecifiedNot Specified
Normal
details
SalivaDetected and Quantified8.04 +/- 0.4 uMAdult (>18 years old)BothNormal
    • Zerihun T. Dame, ...
details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)MaleNormal details
UrineDetected but not QuantifiedNot ApplicableAdult (>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 but not QuantifiedNot ApplicableAdult (>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 Quantified0.53-0.85 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
BiofluidStatusValueAgeSexConditionReferenceDetails
FecesDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Irritable bowel syndrome
details
FecesDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Ulcerative colitis
details
UrineDetected and Quantified6.467 +/- 5.597 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified40.00 (20.00-60.00) umol/mmol creatinineChildren (1-13 years old)BothShort chain acyl-CoA dehydrogenase deficiency (SCAD) 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 Quantified1.5 (0.0-3.0) umol/mmol creatinineAdult (>18 years old)BothEthylmalonic encephalopathy details
UrineDetected and Quantified40.0 (20.0-60.0) umol/mmol creatinineChildren (1-13 years old)BothEthylmalonic encephalopathy 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
Associated Disorders and Diseases
Disease References
Short Chain Acyl-Coa Dehydrogenase Deficiency
  1. MetaGene [Link]
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. [6186413 ]
Ethylmalonic encephalopathy
  1. MetaGene [Link]
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022704
KNApSAcK IDNot Available
Chemspider ID9922
KEGG Compound IDC08645
BioCyc IDDIETHYL-2R3R-2-METHYL-3-HYDROXYSUCCIN
BiGG IDNot Available
Wikipedia LinkNot Available
NuGOwiki LinkHMDB01844
Metagene LinkHMDB01844
METLIN ID6344
PubChem Compound10349
PDB IDNot Available
ChEBI ID29003
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. [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. [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. [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. [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. [15596249 ]