Methylmalonic acid

Methylmalonic acid (MMA) (conjugate base methylmalonate) is a dicarboxylic acid that is a C-methylated derivative of malonate.

Methylmalonic acid

Names
IUPAC name 2-Methylpropanedioic acid
Other names Methylmalonic acid
Identifiers
CAS Number	516-05-2
3D model (JSmol)	Interactive image
ChEBI	CHEBI:30860
ChemSpider	473
ECHA InfoCard	100.007.473
EC Number	208-219-5
KEGG	C02170
MeSH	Methylmalonic+acid
PubChem CID	487
UNII	8LL8S712J7
CompTox Dashboard (EPA)	DTXSID00199549
InChI InChI=1S/C4H6O4/c1-2(3(5)6)4(7)8/h2H,1H3,(H,5,6)(H,7,8) Key: ZIYVHBGGAOATLY-UHFFFAOYSA-N InChI=1/C4H6O4/c1-2(3(5)6)4(7)8/h2H,1H3,(H,5,6)(H,7,8) Key: ZIYVHBGGAOATLY-UHFFFAOYAT
SMILES CC(C(=O)O)C(=O)O
Properties
Chemical formula	C4H6O4
Molar mass	118.088 g/mol
Density	1.455 g/cm^−3
Melting point	134 °C (273 °F; 407 K)
Acidity (pKa)	pKa1 = 3,07[1] pKa2 = 5,76[1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

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, it enters the Krebs cycle, and is thus part of one of the anaplerotic reactions.

Pathology

Increased methylmalonic acid levels may indicate a vitamin B₁₂ deficiency. However, it is sensitive (those with the deficiency almost always test positive) but not specific (those that do not have vitamin B12 deficiency may have elevated levels of methylmalonic acid detected).[2] MMA is elevated in 90–98% of patients with B₁₂ deficiency. It has lower specificity as 20–25% of patients over the age of 70 have elevated levels of MMA, but 25–33% of them do not have B₁₂ deficiency. For this reason, MMA test is not routinely recommended in the elderly.[3] Moreover, recently MMA accumulation in the blood with age had been linked with tumour progression.[4]

An excess is associated with methylmalonic acidemia.

MMA concentrations in blood are measured by gas chromatographic mass spectrometry or LC-MS and the expected values of MMA in healthy people are between 73–271 nmol/l.[5][6]

See also

• Malonic acid

References

1. "Dissociation Constants Of Organic Acids And Bases". zirchrom.com.
2. "Sensitivity and Specificity". www.med.emory.edu.
3. "B12 Deficiency and Dizziness". www.dizziness-and-balance.com.
4. Gomes, Ana P.; Ilter, Didem; Low, Vivien; Endress, Jennifer E.; Fernández-García, Juan; Rosenzweig, Adam; Schild, Tanya; Broekaert, Dorien; Ahmed, Adnan; Planque, Melanie; Elia, Ilaria (2020-09-10). "Age-induced accumulation of methylmalonic acid promotes tumour progression". Nature. 585 (7824): 283–287. doi:10.1038/s41586-020-2630-0. ISSN 0028-0836.
5. Isber, Sonia (2007). "The role of poor nutritional status and hyperhomocysteinemia in complicated pregnancy in Syria" (PDF). doi:10.22028/D291-20838. Cite journal requires |journal= (help)
6. "Methylmalonic Acid, Serum or Plasma (Vitamin B12 Status)". ltd.aruplab.com.

Further reading

• Vitamin B12, cognition, and brain MRI measures: a cross-sectional examination.