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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2018-05-20 09:43:24 UTC
HMDB IDHMDB0000202
Secondary Accession Numbers
  • HMDB00202
Metabolite Identification
Common NameMethylmalonic acid
DescriptionMethylmalonic acid is a malonic acid derivative, which is a vital intermediate in the metabolism of fat and protein. In particular, the coenzyme A-linked form of methylmalonic acid, methylmalonyl-CoA, is converted into succinyl-CoA by methylmalonyl-CoA mutase in a reaction that requires vitamin B12 as a cofactor. In this way, methylmalonic acid enters the Krebs cycle and is thus part of one of the anaplerotic reactions. Abnormalities in methylmalonic acid metabolism lead to methylmalonic aciduria. This inborn error of metabolism is attributed to a block in the enzymatic conversion of methylmalonyl CoA to succinyl CoA. Methylmalonic acid is also found to be associated with other inborn errors of metabolism, including cobalamin deficiency, cobalamin malabsorption, malonyl-CoA decarboxylase deficiency, and transcobalamin II deficiency. When present in sufficiently high levels, methylmalonic 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. Chronically high levels of methylmalonic acid are associated with at least 5 inborn errors of metabolism, including Malonyl CoA decarboxylase deficiency, Malonic Aciduria, Methylmalonate Semialdehyde Dehydrogenase Deficiency, Methylmalonic Aciduria and Methylmalonic Aciduria Due to Cobalamin-Related Disorders. Methylmalonic acid is an organic acid and 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.
Structure
Thumb
Synonyms
ValueSource
1,1-Ethanedicarboxylic acidChEBI
2-Methylmalonic acidChEBI
alpha-Methylmalonic acidChEBI
Isosuccinic acidChEBI
1,1-EthanedicarboxylateGenerator
MethylmalonateGenerator
2-MethylmalonateGenerator
a-MethylmalonateGenerator
a-Methylmalonic acidGenerator
alpha-MethylmalonateGenerator
α-methylmalonateGenerator
α-methylmalonic acidGenerator
IsosuccinateGenerator
Methyl-malonateHMDB
Methyl-malonic acidHMDB
Methyl-propanedioateHMDB
Methyl-propanedioic acidHMDB
MethylpropanedioateHMDB
Methylpropanedioic acidHMDB
Acid, methylmalonicMeSH
Chemical FormulaC4H6O4
Average Molecular Weight118.088
Monoisotopic Molecular Weight118.02660868
IUPAC Name2-methylpropanedioic acid
Traditional Namemethylmalonic acid
CAS Registry Number516-05-2
SMILES
CC(C(O)=O)C(O)=O
InChI Identifier
InChI=1S/C4H6O4/c1-2(3(5)6)4(7)8/h2H,1H3,(H,5,6)(H,7,8)
InChI KeyZIYVHBGGAOATLY-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as dicarboxylic acids and derivatives. These are organic compounds containing exactly two carboxylic acid groups.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassDicarboxylic acids and derivatives
Direct ParentDicarboxylic acids and derivatives
Alternative Parents
Substituents
  • 1,3-dicarbonyl compound
  • Dicarboxylic acid or derivatives
  • Carboxylic acid
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Source:

Biological location:

Process

Naturally occurring process:

Role

Industrial application:

Indirect biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point135 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility679 mg/mLNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility149 g/LALOGPS
logP0.17ALOGPS
logP0.21ChemAxon
logS0.1ALOGPS
pKa (Strongest Acidic)2.48ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.6 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity23.56 m³·mol⁻¹ChemAxon
Polarizability10.06 ųChemAxon
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) (2 TMS)splash10-0002-1910000000-cf95dd8a481761a28664View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (2 TMS)splash10-006t-8900000000-4d8795e7e4300cc7ceffView in MoNA
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-00lr-5940000000-56b86ada220d335ce30aView in MoNA
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-001i-9301000000-54e5247d046de566ac1eView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-004i-9000000000-b9ee59dddf90dfc7c461View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0002-1910000000-cf95dd8a481761a28664View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-006t-8900000000-4d8795e7e4300cc7ceffView in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-001i-9301000000-54e5247d046de566ac1eView in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-00lr-5940000000-56b86ada220d335ce30aView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0002-0900000000-684a11ce99cccbd9194aView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0g4i-9400000000-baa4ea6d613ebb8bffc7View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00dr-9310000000-a99f1bb4adbde62446d9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Negative (Annotated)splash10-00di-9000000000-1578bea9a6b8b12e2f9bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Negative (Annotated)splash10-05fr-9000000000-0e443f81ee9c6c9b1fa5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Negative (Annotated)splash10-0ab9-9100000000-d23d6a0a35141ed9a950View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-01b9-6900000000-6d969044a89f00e1b46fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-00di-9000000000-0f655174050263224e67View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-0ab9-9000000000-26a654fb133b28a816a0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-0a4i-9000000000-7afd566e443d5fa38887View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-0a4i-9000000000-5c4795e954d5c3e9b74eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-01b9-6900000000-6d969044a89f00e1b46fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-00di-9000000000-0f655174050263224e67View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0ab9-9000000000-26a654fb133b28a816a0View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4i-9000000000-7afd566e443d5fa38887View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4i-9000000000-5c4795e954d5c3e9b74eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-5900000000-9b75ec910fa494f0ad6aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-05di-9200000000-87a71ae13cf70d990bb1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-004i-9000000000-e7ae04912b5ee745a992View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-4900000000-0714f0bc5c29e5d61ac4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-9100000000-ecfebddbd3d8f7224994View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05fr-9000000000-506ee5ec2100e13e09ceView in MoNA
MSMass Spectrum (Electron Ionization)splash10-05di-9000000000-8d09b408489f7b1743b5View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Urine
Tissue Location
  • Kidney
  • Liver
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.14 (0.04-0.26) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.187 +/- 0.084 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified<0.28 uMChildren (1-13 years old)Not SpecifiedNormal details
BloodDetected and Quantified<0.33 uMChildren (1-13 years old)Not SpecifiedNormal details
BloodDetected and Quantified<0.4 uMAdult (>18 years old)Not SpecifiedNormal details
BloodDetected and Quantified<0.27 uMInfant (0-1 year old)BothNormal details
BloodDetected and Quantified0.17 (0.073-0.27) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified<0.34 uMAdolescent (13-18 years old)FemaleNormal details
BloodDetected and Quantified0.200 (0.00-0.400) uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.15-0.55 uMAdolescent (13-18 years old)FemaleNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.40 (0.16-0.59) uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.51 +/- 0.13 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.32 +/- 0.11 uMAdult (>18 years old)BothNormal details
FecesDetected but not Quantified Adult (>18 years old)Both
Normal
details
UrineDetected and Quantified<3 umol/mmol creatinineAdult (>18 years old)Not SpecifiedNormal details
UrineDetected and Quantified<5.130 umol/mmol creatinineInfant (0-1 year old)Not SpecifiedNormal details
UrineDetected but not Quantified Adult (>18 years old)BothNormal details
UrineDetected and Quantified3.495 +/- 2.595 umol/mmol creatinineAdult (>18 years old)BothNot Available details
UrineDetected and Quantified9.247 +/- 8.216 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected and Quantified0.92 +/- 1.97 umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected but not Quantified Adult (>18 years old)Both
Normal
details
UrineDetected but not Quantified Adult (>18 years old)BothNormal details
UrineDetected and Quantified1.58 (0.0-3.29) umol/mmol creatinineAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
UrineDetected and Quantified2.0 +/- 0.7 umol/mmol creatinineNewborn (0-30 days old)BothNormal
    • Geigy Scientific ...
details
UrineDetected and Quantified4.0 +/- 0.9 umol/mmol creatinineChildren (1-13 years old)BothNormal
    • Geigy Scientific ...
details
UrineDetected and Quantified1.7-2.8 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified<5.13 umol/mmol creatinineChildren (1 - 18 years old)Both
Normal
    • BC Children's Hos...
details
UrineDetected and Quantified1.8 (0.00-3.6) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified2.50 umol/mmol creatinineAdult (>18 years old)MaleNormal
    • Shaykhutdinov RA,...
details
UrineDetected and Quantified1.9 (0.7-3.5) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified0.64 +/- 0.39 umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected and Quantified0.17 +/- 0.11 umol/mmol creatinineAdolescent (13-18 years old)Both
Normal
details
UrineDetected and Quantified2.51 +/- 1.01 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified<0.07 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified<47.871 umol/mmol creatinineInfant (0-1 year old)MaleNormal details
UrineDetected and Quantified<6 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified1.5-2.4 umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified0.765 +/- 0.896 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Normal
    • Mordechai, Hien, ...
details
UrineDetected and Quantified1.6 (0-3.6) umol/mmol creatinineAdult (>18 years old)Not SpecifiedNormal details
UrineDetected and Quantified9.4 (0.1-79.4) umol/mmol creatinineNewborn (0-30 days old)BothNormal details
UrineDetected and Quantified<3.6 umol/mmol creatinineChildren (1-13 years old)Not SpecifiedNormal details
UrineDetected and Quantified29.9 (0.1-78.9) umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified<5 umol/mmol creatinineChildren (1-13 years old)Not SpecifiedNormal details
UrineDetected and Quantified<4 umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified8.2 (1.5-30.8) umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected and Quantified3.7 (1.1-21.6) umol/mmol creatinineAdolescent (13-18 years old)BothNormal details
UrineDetected and Quantified1.3 (0.5-2.1) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.466-188.842 uMAdult (>18 years old)Bothcobalamin deficiency details
BloodDetected and Quantified11.2 uMAdult (>18 years old)BothHeart Transplant details
BloodDetected and Quantified22.0 (4.3-37.0) uMAdult (>18 years old)BothCobalamin deficiency details
BloodDetected and Quantified0.480 +/- 0.062 uMAdult (>18 years old)BothAlzheimer's disease details
BloodDetected and Quantified10-15.4 uMAdult (>18 years old)BothCombined malonic and methylmalonic aciduria details
BloodDetected and Quantified1.3-4.1 uMChildren (1-13 years old)BothMethylmalonic aciduria mitochondrial encephelopathy Leigh-like details
BloodDetected and Quantified5-100 uMInfant (0-1 year old)BothMethylmalonic aciduria, cblA type details
BloodDetected and Quantified5-100 uMInfant (0-1 year old)BothMethylmalonic aciduria, cblB type details
BloodDetected and Quantified0.8-33 uMChildren (1-13 years old)BothMitochondrial encephalomyopaththy with elevanted methylmalonic acid, SUCLA2 details
BloodDetected and Quantified2.8 uMAdolescent (13-18 years old)FemaleMalonyl-CoA decarboxylase deficiency details
Cerebrospinal Fluid (CSF)Detected and Quantified13 uMAdolescent (13-18 years old)FemaleMalonyl-CoA decarboxylase deficiency details
Cerebrospinal Fluid (CSF)Detected and Quantified0.30 +/- 0.12 uMElderly (>65 years old)Not SpecifiedAlzheimer's disease details
UrineDetected and Quantified29.200-104.500 umol/mmol creatinineAdult (>18 years old)BothCombined malonic and methylmalonic aciduria details
UrineDetected and Quantified10.435 +/- 7.593 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified16.0 (1.5-30.8) umol/mmol creatinineAdult (>18 years old)BothCobalamin malabsorption
    • MetaGene: Metabol...
details
UrineDetected and Quantified275.0 (50.0-500.0) umol/mmol creatinineChildren (1-13 years old)BothCobalamin malabsorption
    • MetaGene: Metabol...
details
UrineDetected and Quantified0 umol/mmol creatinineAdult (>18 years old)Not Specified
Propionic acidemia
details
UrineDetected and Quantified0.05 umol/mmol creatinineAdult (>18 years old)Not Specified
Propionic acidemia
details
UrineDetected and Quantified3.83 umol/mmol creatinineInfant (0-1 year old)MaleFumarase deficiency details
UrineDetected and Quantified33 umol/mmol creatinineInfant (0-1 year old)MaleMalonyl-Coa decarboxylase deficiency details
UrineDetected and Quantified126-904 umol/mmol creatinineNewborn (0-30 days old)FemaleTranscobalamin II deficiency details
UrineDetected and Quantified97.67 +/- 89.432 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified17.779 +/- 21.646 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Gastroesophageal reflux disease
    • Mordechai, Hien, ...
details
UrineDetected and Quantified16-80 umol/mmol creatinineChildren (1-13 years old)BothMethylmalonic aciduria mitochondrial encephelopathy Leigh-like details
UrineDetected and Quantified10-100 umol/mmol creatinineInfant (0-1 year old)BothMethylmalonic aciduria, cblA type details
UrineDetected and Quantified10-100 umol/mmol creatinineInfant (0-1 year old)BothMethylmalonic aciduria, cblB type details
UrineDetected and Quantified51-212 umol/mmol creatinineChildren (1-13 years old)BothMitochondrial encephalomyopaththy with elevanted methylmalonic acid, SUCLA2 details
UrineDetected and Quantified200 umol/mmol creatinineInfant (0-1 year old)FemaleCobalamin F disease (cblF) details
Associated Disorders and Diseases
Disease References
Alzheimer's disease
  1. Serot JM, Barbe F, Arning E, Bottiglieri T, Franck P, Montagne P, Nicolas JP: Homocysteine and methylmalonic acid concentrations in cerebrospinal fluid: relation with age and Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2005 Nov;76(11):1585-7. [PubMed:16227558 ]
  2. Kristensen MO, Gulmann NC, Christensen JE, Ostergaard K, Rasmussen K: Serum cobalamin and methylmalonic acid in Alzheimer dementia. Acta Neurol Scand. 1993 Jun;87(6):475-81. [PubMed:8356878 ]
Vitamin B12 deficiency
  1. 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 ]
  2. Stabler SP, Marcell PD, Podell ER, Allen RH, Lindenbaum J: Assay of methylmalonic acid in the serum of patients with cobalamin deficiency using capillary gas chromatography-mass spectrometry. J Clin Invest. 1986 May;77(5):1606-12. [PubMed:3700655 ]
Fumarase deficiency
  1. Bastug O, Kardas F, Ozturk MA, Halis H, Memur S, Korkmaz L, Tag Z, Gunes T: A rare cause of opistotonus; fumaric aciduria: The first case presentation in Turkey. Turk Pediatri Ars. 2014 Mar 1;49(1):74-6. doi: 10.5152/tpa.2014.442. eCollection 2014 Mar. [PubMed:26078636 ]
Malonyl-Coa decarboxylase deficiency
  1. Polinati PP, Valanne L, Tyni T: Malonyl-CoA decarboxylase deficiency: long-term follow-up of a patient new clinical features and novel mutations. Brain Dev. 2015 Jan;37(1):107-13. doi: 10.1016/j.braindev.2014.02.001. Epub 2014 Mar 7. [PubMed:24613099 ]
  2. Haan EA, Scholem RD, Croll HB, Brown GK: Malonyl coenzyme A decarboxylase deficiency. Clinical and biochemical findings in a second child with a more severe enzyme defect. Eur J Pediatr. 1986 Apr;144(6):567-70. [PubMed:3709568 ]
Propionic acidemia
  1. Riemersma M, Hazebroek MR, Helderman-van den Enden ATJM, Salomons GS, Ferdinandusse S, Brouwers MCGJ, van der Ploeg L, Heymans S, Glatz JFC, van den Wijngaard A, Krapels IPC, Bierau J, Brunner HG: Propionic acidemia as a cause of adult-onset dilated cardiomyopathy. Eur J Hum Genet. 2017 Nov;25(11):1195-1201. doi: 10.1038/ejhg.2017.127. Epub 2017 Aug 30. [PubMed:28853722 ]
Transcobalamin II deficiency
  1. Bibi H, Gelman-Kohan Z, Baumgartner ER, Rosenblatt DS: Transcobalamin II deficiency with methylmalonic aciduria in three sisters. J Inherit Metab Dis. 1999 Oct;22(7):765-72. [PubMed:10518276 ]
Cobalamin malabsorption
  1. G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
Eosinophilic esophagitis
  1. (). Mordechai, Hien, and David S. Wishart. .
Cobalamin F disease (cblF)
  1. Alfadhel M, Lillquist YP, Davis C, Junker AK, Stockler-Ipsiroglu S: Eighteen-year follow-up of a patient with cobalamin F disease (cblF): report and review. Am J Med Genet A. 2011 Oct;155A(10):2571-7. doi: 10.1002/ajmg.a.34220. Epub 2011 Sep 9. [PubMed:21910240 ]
Combined malonic and methylmalonic aciduria
  1. Sloan JL, Johnston JJ, Manoli I, Chandler RJ, Krause C, Carrillo-Carrasco N, Chandrasekaran SD, Sysol JR, O'Brien K, Hauser NS, Sapp JC, Dorward HM, Huizing M, Barshop BA, Berry SA, James PM, Champaigne NL, de Lonlay P, Valayannopoulos V, Geschwind MD, Gavrilov DK, Nyhan WL, Biesecker LG, Venditti CP: Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria. Nat Genet. 2011 Aug 14;43(9):883-6. doi: 10.1038/ng.908. [PubMed:21841779 ]
Methylmalonic aciduria mitochondrial encephelopathy Leigh-like
  1. Carrozzo R, Dionisi-Vici C, Steuerwald U, Lucioli S, Deodato F, Di Giandomenico S, Bertini E, Franke B, Kluijtmans LA, Meschini MC, Rizzo C, Piemonte F, Rodenburg R, Santer R, Santorelli FM, van Rooij A, Vermunt-de Koning D, Morava E, Wevers RA: SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness. Brain. 2007 Mar;130(Pt 3):862-74. Epub 2007 Feb 14. [PubMed:17301081 ]
Methylmalonic aciduria, cblA type
  1. Keyfi F, Talebi S, Varasteh AR: Methylmalonic Acidemia Diagnosis by Laboratory Methods. Rep Biochem Mol Biol. 2016 Oct;5(1):1-14. [PubMed:28070528 ]
Methylmalonic aciduria, cblB type
  1. Keyfi F, Talebi S, Varasteh AR: Methylmalonic Acidemia Diagnosis by Laboratory Methods. Rep Biochem Mol Biol. 2016 Oct;5(1):1-14. [PubMed:28070528 ]
Mitochondrial encephalomyopaththy with elevanted methylmalonic acid, SUCLA2
  1. Ostergaard E, Hansen FJ, Sorensen N, Duno M, Vissing J, Larsen PL, Faeroe O, Thorgrimsson S, Wibrand F, Christensen E, Schwartz M: Mitochondrial encephalomyopathy with elevated methylmalonic acid is caused by SUCLA2 mutations. Brain. 2007 Mar;130(Pt 3):853-61. Epub 2007 Feb 7. [PubMed:17287286 ]
Associated OMIM IDs
  • 248360 (Malonyl-Coa decarboxylase deficiency)
  • 251100 (Methylmalonic aciduria, cblA type)
  • 251110 (Methylmalonic aciduria, cblB type)
  • 612073 (Mitochondrial encephalomyopaththy with elevanted methylmalonic acid, SUCLA2)
  • 104300 (Alzheimer's disease)
  • 610247 (Eosinophilic esophagitis)
  • 606054 (Propionic acidemia)
  • 606812 (Fumarase deficiency)
  • 275350 (Transcobalamin II deficiency)
  • 277380 (Cobalamin F disease (cblF))
  • 614265 (Combined malonic and methylmalonic aciduria)
DrugBank IDDB04183
Phenol Explorer Compound IDNot Available
FoodDB IDFDB021905
KNApSAcK IDNot Available
Chemspider ID473
KEGG Compound IDC02170
BioCyc IDCPD-546
BiGG IDNot Available
Wikipedia LinkMethylmalonic_acid
METLIN ID3712
PubChem Compound487
PDB IDDXX
ChEBI ID30860
References
Synthesis ReferenceEdamura, Koji; Arai, Takeshi. Malonic and methylmalonic acids from b-hydroxypropionic acids. Jpn. Kokai Tokkyo Koho (1979), 5 pp.
Material Safety Data Sheet (MSDS)Not Available
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. Haurani FI, Hall CA, Rubin R: Megaloblastic anemia as a result of an abnormal transcobalamin II (Cardeza). J Clin Invest. 1979 Nov;64(5):1253-9. [PubMed:500809 ]
  3. Bennett MJ, Ragni MC, Hood I, Hale DE: Comparison of post-mortem urinary and vitreous humour organic acids. Ann Clin Biochem. 1992 Sep;29 ( Pt 5):541-5. [PubMed:1444166 ]
  4. van Asselt DZ, Karlietis MH, Poels PJ, de Jong JG, Wevers RA, Hoefnagels WH: Cerebrospinal fluid methylmalonic acid concentrations in neurological patients with low and normal serum cobalamin concentrations. Acta Neurol Scand. 1998 Jun;97(6):413-6. [PubMed:9669477 ]
  5. Magera MJ, Helgeson JK, Matern D, Rinaldo P: Methylmalonic acid measured in plasma and urine by stable-isotope dilution and electrospray tandem mass spectrometry. Clin Chem. 2000 Nov;46(11):1804-10. [PubMed:11067816 ]
  6. Nakamura E, Rosenberg LE, Tanaka K: Microdetermination of methylmalonic acid and other short chain dicarboxylic acids by gas chromatography: use in prenatal diagnosis of methylmalonic acidemia and in studies of isovaleric acidemia. Clin Chim Acta. 1976 Apr 15;68(2):127-40. [PubMed:1261058 ]
  7. Jakobs C, Sweetman L, Nyhan WL: Hydroxy acid metabolites of branched-chain amino acids in amniotic fluid. Clin Chim Acta. 1984 Jul 16;140(2):157-66. [PubMed:6467607 ]
  8. Coude MM, Charpentier C, Bonnefont JP, Cheron G, Kamoun P: Organic acids in aqueous humour and plasma: post mortem study in infants and diagnosis of enzymopathies. J Inherit Metab Dis. 1991;14(5):668-73. [PubMed:1779612 ]
  9. Aleszczyk J: [Connection between changing the vitamin and immune status and the character of the throat microflora in patients with chronic tonsillitis]. Otolaryngol Pol. 2003;57(2):221-4. [PubMed:12894427 ]
  10. Nagarajan S, Enns GM, Millan MT, Winter S, Sarwal MM: Management of methylmalonic acidaemia by combined liver-kidney transplantation. J Inherit Metab Dis. 2005;28(4):517-24. [PubMed:15902554 ]
  11. Stabler SP, Marcell PD, Podell ER, Allen RH, Lindenbaum J: Assay of methylmalonic acid in the serum of patients with cobalamin deficiency using capillary gas chromatography-mass spectrometry. J Clin Invest. 1986 May;77(5):1606-12. [PubMed:3700655 ]
  12. Jellum E, Stokke O, Eldjarn L: Combined use of gas chromatography, mass spectrometry, and computer in diagnosis and studies of metabolic disorders. Clin Chem. 1972 Aug;18(8):800-9. [PubMed:4557757 ]
  13. Leupold D: [Methylmalonic aciduria. Classification, diagnosis and therapy (author's transl)]. Klin Wochenschr. 1977 Jan 15;55(2):57-63. [PubMed:319293 ]
  14. Vrethem M, Mattsson E, Hebelka H, Leerbeck K, Osterberg A, Landtblom AM, Balla B, Nilsson H, Hultgren M, Brattstrom L, Kagedal B: Increased plasma homocysteine levels without signs of vitamin B12 deficiency in patients with multiple sclerosis assessed by blood and cerebrospinal fluid homocysteine and methylmalonic acid. Mult Scler. 2003 Jun;9(3):239-45. [PubMed:12814169 ]
  15. Frenkel EP, Kitchens RL: Applicability of an enzymatic quantitation of methylmalonic, propionic, and acetic acids in normal and megaloblastic states. Blood. 1977 Jan;49(1):125-37. [PubMed:830370 ]

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
Not Available
Gene Name:
AOX1
Uniprot ID:
Q06278
Molecular weight:
147916.735
Reactions
Methylmalonic acid + Hydrogen peroxide → (S)-Methylmalonic acid semialdehyde + Oxygen + Waterdetails
General function:
Involved in oxidoreductase activity
Specific function:
Converts gamma-trimethylaminobutyraldehyde into gamma-butyrobetaine. Catalyzes the irreversible oxidation of a broad range of aldehydes to the corresponding acids in an NAD-dependent reaction.
Gene Name:
ALDH9A1
Uniprot ID:
P49189
Molecular weight:
56291.485
Reactions
(S)-Methylmalonic acid semialdehyde + NAD + Water → Methylmalonic acid + NADH + Hydrogen Iondetails
General function:
Involved in oxidoreductase activity
Specific function:
Multifunctional enzyme mediating important protective effects. Metabolizes betaine aldehyde to betaine, an important cellular osmolyte and methyl donor. Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes. Involved in lysine catabolism.
Gene Name:
ALDH7A1
Uniprot ID:
P49419
Molecular weight:
58486.74
Reactions
(S)-Methylmalonic acid semialdehyde + NAD + Water → Methylmalonic acid + NADH + Hydrogen Iondetails
General function:
Involved in oxidoreductase activity
Specific function:
Recognizes as substrates free retinal and cellular retinol-binding protein-bound retinal. Seems to be the key enzyme in the formation of an RA gradient along the dorso-ventral axis during the early eye development and also in the development of the olfactory system (By similarity).
Gene Name:
ALDH1A3
Uniprot ID:
P47895
Molecular weight:
56107.995
General function:
Involved in oxidoreductase activity
Specific function:
Not Available
Gene Name:
ALDH2
Uniprot ID:
P05091
Molecular weight:
56380.93
Reactions
(S)-Methylmalonic acid semialdehyde + NAD + Water → Methylmalonic acid + NADH + Hydrogen Iondetails
General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acids. Active on a variety of saturated and unsaturated aliphatic aldehydes between 6 and 24 carbons in length. Responsible for conversion of the sphingosine 1-phosphate (S1P) degradation product hexadecenal to hexadecenoic acid.
Gene Name:
ALDH3A2
Uniprot ID:
P51648
Molecular weight:
54847.36
Reactions
(S)-Methylmalonic acid semialdehyde + NAD + Water → Methylmalonic acid + NADH + Hydrogen Iondetails
General function:
Involved in oxidoreductase activity
Specific function:
ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde. They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation.
Gene Name:
ALDH1B1
Uniprot ID:
P30837
Molecular weight:
57248.96
Reactions
(S)-Methylmalonic acid semialdehyde + NAD + Water → Methylmalonic acid + NADH + Hydrogen Iondetails