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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-06-10 21:22:57 UTC
HMDB IDHMDB00202
Secondary Accession NumbersNone
Metabolite Identification
Common NameMethylmalonic acid
DescriptionMethylmalonic acid is a malonic acid derivative which is a vital intermediate in the metabolism of fat and protein. Abnormalities in methylmalonic acid metabolism lead to methylmalonic aciduria. This metabolic disease is attributed to a block in the enzymatic conversion of methylmalonyl CoA to succinyl CoA.
Structure
Thumb
Synonyms
ValueSource
1,1-Ethanedicarboxylic acidChEBI
2-Methylmalonic acidChEBI
alpha-Methylmalonic acidChEBI
Isosuccinic acidChEBI
1,1-EthanedicarboxylateGenerator
2-MethylpropanedioateGenerator
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
MethylmalonateHMDB
MethylpropanedioateHMDB
Methylpropanedioic acidHMDB
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 KeyInChIKey=ZIYVHBGGAOATLY-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
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
BiofunctionNot Available
ApplicationNot Available
Cellular locations
  • Cytoplasm (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point135 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility679.0 mg/mLNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility149.0 mg/mLALOGPS
logP0.17ALOGPS
logP0.21ChemAxon
logS0.1ALOGPS
pKa (Strongest Acidic)2.48ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.6 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity23.56 m3·mol-1ChemAxon
Polarizability10.06 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) (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 - GC-MSNot Available
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
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
MSMass Spectrum (Electron Ionization)splash10-05di-9000000000-8d09b408489f7b1743b5View in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR13C 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
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Kidney
  • Liver
Pathways
NameSMPDB LinkKEGG Link
2-Methyl-3-Hydroxybutryl CoA Dehydrogenase DeficiencySMP00137Not Available
3-Hydroxy-3-Methylglutaryl-CoA Lyase DeficiencySMP00138Not Available
3-hydroxyisobutyric acid dehydrogenase deficiencySMP00521Not Available
3-hydroxyisobutyric aciduriaSMP00522Not Available
3-Methylcrotonyl Coa Carboxylase Deficiency Type ISMP00237Not Available
3-Methylglutaconic Aciduria Type ISMP00139Not Available
3-Methylglutaconic Aciduria Type IIISMP00140Not Available
3-Methylglutaconic Aciduria Type IVSMP00141Not Available
Beta-Ketothiolase DeficiencySMP00173Not Available
Isobutyryl-coa dehydrogenase deficiencySMP00523Not Available
Isovaleric acidemiaSMP00524Not Available
Isovaleric AciduriaSMP00238Not Available
Malonic AciduriaSMP00198Not Available
Malonyl-coa decarboxylase deficiencySMP00502Not Available
Maple Syrup Urine DiseaseSMP00199Not Available
Methylmalonate Semialdehyde Dehydrogenase DeficiencySMP00384Not Available
Methylmalonic AciduriaSMP00200Not Available
Methylmalonic Aciduria Due to Cobalamin-Related DisordersSMP00201Not Available
Propanoate MetabolismSMP00016map00640
Propionic AcidemiaSMP00236Not Available
Valine, Leucine and Isoleucine DegradationSMP00032map00280
Vitamin K MetabolismSMP00464Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
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 Quantified0.17 (0.073-0.27) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.200 (0.00-0.400) uMAdult (>18 years old)Not SpecifiedNormal 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
UrineDetected but not QuantifiedNot ApplicableAdult (>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 QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
UrineDetected but not QuantifiedNot ApplicableAdult (>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 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 Quantified29.9 (0.1-78.9) 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
BiofluidStatusValueAgeSexConditionReferenceDetails
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
Cerebrospinal Fluid (CSF)Detected and Quantified0.30 +/- 0.12 uMElderly (>65 years old)Not SpecifiedAlzheimer's disease details
UrineDetected and Quantified10.435 +/- 7.593 umol/mmol creatinineChildren (1 - 13 years old)Not Specified
Eosinophilic esophagitis
    • Mordechai, Hien, ...
details
UrineDetected and Quantified325.00 (150.00-500.00) umol/mmol creatinineChildren (1-13 years old)BothTranscobalamin II deficiency details
UrineDetected and Quantified16.0 (1.5-30.8) umol/mmol creatinineAdult (>18 years old)BothCobalamin malabsorption details
UrineDetected and Quantified275.0 (50.0-500.0) umol/mmol creatinineChildren (1-13 years old)BothCobalamin malabsorption 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 Quantified7825.00 (150.00-15500.00) umol/mmol creatinineChildren (1-13 years old)BothMalonyl-CoA decarboxylase deficiency 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. [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. [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. [8412012 ]
Malonyl-Coa decarboxylase deficiency
  1. MetaGene [Link]
Transcobalamin II deficiency
  1. MetaGene [Link]
Cobalamin malabsorption
  1. MetaGene [Link]
Associated OMIM IDs
  • 104300 (Alzheimer's disease)
  • 248360 (Malonyl-Coa decarboxylase deficiency)
  • 275350 (Transcobalamin II deficiency)
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB021905
KNApSAcK IDNot Available
Chemspider ID473
KEGG Compound IDC02170
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkMethylmalonic acid
NuGOwiki LinkHMDB00202
Metagene LinkHMDB00202
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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [4557757 ]
  13. Leupold D: [Methylmalonic aciduria. Classification, diagnosis and therapy (author's transl)] Klin Wochenschr. 1977 Jan 15;55(2):57-63. [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. [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. [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