| Record Information |
|---|
| Version | 2.0 |
|---|
| Created at | 2005-11-16 15:48:42 UTC |
|---|
| Updated at | 2025-02-11 15:40:57 UTC |
|---|
| NP-MRD ID | NP0000555 |
|---|
| Secondary Accession Numbers | None |
|---|
| Natural Product Identification |
|---|
| Common Name | Methylmalonic acid |
|---|
| Description | Methylmalonic 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. | Read more...
|---|
| Structure | InChI=1S/C4H6O4/c1-2(3(5)6)4(7)8/h2H,1H3,(H,5,6)(H,7,8) |
|---|
| Synonyms | | Value | Source |
|---|
| 1,1-Ethanedicarboxylic acid | ChEBI | | 2-Methylmalonic acid | ChEBI | | alpha-Methylmalonic acid | ChEBI | | Isosuccinic acid | ChEBI | | 1,1-Ethanedicarboxylate | Generator | | 2-Methylmalonate | Generator | | a-Methylmalonate | Generator | | a-Methylmalonic acid | Generator | | alpha-Methylmalonate | Generator | | Α-methylmalonate | Generator | | Α-methylmalonic acid | Generator | | Isosuccinate | Generator | | Methylmalonate | Generator | | Methyl-malonate | HMDB | | Methyl-malonic acid | HMDB | | Methyl-propanedioate | HMDB | | Methyl-propanedioic acid | HMDB | | Methylpropanedioate | HMDB | | Methylpropanedioic acid | HMDB | | Acid, methylmalonic | HMDB | | Methylmalonic acid | KEGG |
| Show more...
|---|
| Chemical Formula | C4H6O4 |
|---|
| Average Mass | 118.0880 Da |
|---|
| Monoisotopic Mass | 118.02661 Da |
|---|
| IUPAC Name | 2-methylpropanedioic acid |
|---|
| Traditional Name | methylmalonic acid |
|---|
| CAS Registry Number | 516-05-2 |
|---|
| 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 Key | ZIYVHBGGAOATLY-UHFFFAOYSA-N |
|---|
| Experimental Spectra |
|---|
|
| | Spectrum Type | Description | Depositor Email | Depositor Organization | Depositor | Deposition Date | View |
|---|
| 1D NMR | 1H NMR Spectrum (1D, 500 MHz, H2O, experimental) | Wishart Lab | Wishart Lab | David Wishart | 2021-06-20 | View Spectrum | | 2D NMR | [1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental) | Wishart Lab | Wishart Lab | David Wishart | 2021-06-20 | View Spectrum |
|
|---|
| Predicted Spectra |
|---|
|
| Not Available |
|---|
| Chemical Shift Submissions |
|---|
|
| | Spectrum Type | Description | Depositor Email | Depositor Organization | Depositor | Deposition Date | View |
|---|
| 1D NMR | 13C NMR Spectrum (1D, 400 MHz, H2O, simulated) | varshavi.d26@gmail.com | Not Available | Not Available | 2021-08-02 | View Spectrum |
|
|---|
| Species |
|---|
| Species of Origin | | Show more...
|---|
| Species Where Detected | |
|---|
| Chemical Taxonomy |
|---|
| Description | Belongs to the class of organic compounds known as dicarboxylic acids and derivatives. These are organic compounds containing exactly two carboxylic acid groups. |
|---|
| Kingdom | Organic compounds |
|---|
| Super Class | Organic acids and derivatives |
|---|
| Class | Carboxylic acids and derivatives |
|---|
| Sub Class | Dicarboxylic acids and derivatives |
|---|
| Direct Parent | Dicarboxylic 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 Framework | Aliphatic acyclic compounds |
|---|
| External Descriptors | |
|---|
| Physical Properties |
|---|
| State | Solid |
|---|
| Experimental Properties | | Property | Value | Reference |
|---|
| Melting Point | 135 °C | Not Available | | Boiling Point | Not Available | Not Available | | Water Solubility | 679 mg/mL | Not Available | | LogP | Not Available | Not Available |
|
|---|
| Predicted Properties | |
|---|
| External Links |
|---|
| HMDB ID | HMDB0000202 |
|---|
| DrugBank ID | DB04183 |
|---|
| Phenol Explorer Compound ID | Not Available |
|---|
| FoodDB ID | FDB021905 |
|---|
| KNApSAcK ID | C00052349 |
|---|
| Chemspider ID | 473 |
|---|
| KEGG Compound ID | C02170 |
|---|
| BioCyc ID | CPD-546 |
|---|
| BiGG ID | Not Available |
|---|
| Wikipedia Link | Methylmalonic_acid |
|---|
| METLIN ID | 3712 |
|---|
| PubChem Compound | 487 |
|---|
| PDB ID | Not Available |
|---|
| ChEBI ID | 30860 |
|---|
| Good Scents ID | Not Available |
|---|
| References |
|---|
| General References | - 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- Leupold D: [Methylmalonic aciduria. Classification, diagnosis and therapy (author's transl)]. Klin Wochenschr. 1977 Jan 15;55(2):57-63. [PubMed:319293 ]
- 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 ]
- 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 ]
| Show more...
|---|
