Methylmalonate (Synonyms: Isosuccinic Acid, Methylmalonate, MMA, NSC 25201) |
رقم الكتالوجGC13670
One-Click Copy Product Info
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ميثيل مالونات (ميثيل مالونات) هو مؤشر على نقص فيتامين ب 12 في السرطان.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 516-05-2
Sample solution is provided at 25 µL, 10mM.
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Methylmalonate is a dicarboxylic acid metabolite derived from the propionate metabolic pathway. Methylmalonate can affect cellular metabolism and inflammatory states. Methylmalonate accumulates when vitamin B12-dependent methylmalonyl-CoA mutase is deficient or when vitamin B12 is lacking. Methylmalonate acts through competitive inhibition of succinate dehydrogenase, activation of the SUCNR1 receptor, and mediation of post-translational modifications such as protein methylmalonylation. Methylmalonate can be used in studies of methylmalonic acidemia, vitamin B12 deficiency-related metabolism, aging and age-related chronic diseases, neurotoxicity models, and cancer metabolism[1-4].
In vitro, treatment of fetal cortical neurons with 10mM Methylmalonate for 24 hours led to neuronal death and induced both necrosis and apoptosis[5]. Co-treatment of SH-SY5Y cells with 1mM Methylmalonate and 10µM all-trans-retinoic acid for 7 days reduced basal respiration, ATP-linked respiration, and maximal respiration, and downregulated mRNA expression of mature neuronal marker genes ENO2 and SYP[6]. Treatment of human neuroblastoma SH-SY5Y cells with 0.5-2mM Methylmalonate for 7 days reduced cellular CoQ10 levels, decreased mitochondrial respiratory chain complex II-III activity, and was accompanied by loss of cell viability[7].
In vivo, intraperitoneal injection of Methylmalonate into Wistar rats (first dose 10μmol/g; followed by two doses 5μmol/g; 90-minute intervals; brains collected 60 minutes after the last injection) or intracerebroventricular injection of 2μL 16μmol Methylmalonate (brains collected 30 minutes after injection) decreased reduced glutathione levels in the cerebral cortex and striatum and altered the activities of antioxidant enzymes such as SOD, CAT, GPx, and GST[8]. A single injection of 6µmol/2µl Methylmalonate into the right striatum of adult male Wistar rats induced clonic convulsions and electroencephalographic seizures lasting approximately 2 hours[9]. Subcutaneous injection of 0.76μmol/g Methylmalonate into Wistar rats (aged 5 to 25 days; twice daily; 8-hour intervals) for 5 consecutive days, or subcutaneous injection of 1.20μmol/g Methylmalonate into 10-day-old Wistar rats (three times daily; 1-hour intervals) for 8 consecutive days, decreased Na+,K+-ATPase activity in synaptic plasma membranes of the cerebral cortex[10].
References:
[1] Brismar J, Ozand PT. CT and MR of the brain in disorders of the propionate and methylmalonate metabolism. AJNR Am J Neuroradiol. 1994 Sep;15(8):1459-73.
[2] Wajner M, Coelho JC. Neurological dysfunction in methylmalonic acidaemia is probably related to the inhibitory effect of methylmalonate on brain energy production. J Inherit Metab Dis. 1997 Nov;20(6):761-8.
[3] BARNESS LA, YOUNG DG, NOCHO R. Methylmalonate excretion in vitamin B12 deficiency. Science. 1963 Apr 5;140(3562):76-7.
[4] Talfournier F, Stines-Chaumeil C, Branlant G. Methylmalonate-semialdehyde dehydrogenase from Bacillus subtilis: substrate specificity and coenzyme A binding. J Biol Chem. 2011 Jun 24;286(25):21971-81.
[5] McLaughlin BA, Nelson D, Silver IA, et al. Methylmalonate toxicity in primary neuronal cultures. Neuroscience. 1998;86(1):279-290.
[6] da Costa RT, dos Santos MB, Silva ICS, et al. Methylmalonic Acid Compromises Respiration and Reduces the Expression of Differentiation Markers of SH-SY5Y Human Neuroblastoma Cells. ACS Chem Neurosci. 2021 Aug 18;12(16):2608-2618.
[7] Proctor EC, Turton N, Boan EJ, et al. The Effect of Methylmalonic Acid Treatment on Human Neuronal Cell Coenzyme Q10 Status and Mitochondrial Function. Int J Mol Sci. 2020 Nov;21(23):9137.
[8] Silveira J, Marcuzzo MB, Gayger-Dias V, et al. Antioxidant System Disturbances, Bioenergetic Disruption, and Glial Reactivity Induced by Methylmalonic Acid in the Developing Rat Brain. Neuroglia. 2025 Jun;6(3):25.
[9] Malfatti CRM, Royes LFF, Francescato L, et al. Intrastriatal Methylmalonic Acid Administration Induces Convulsions and TBARS Production, and Alters Na+,K+-ATPase Activity in the Rat Striatum and Cerebral Cortex. Epilepsia. 2003;44(6):761-767.
[10] Wyse ATS, Streck EL, Barros SVT, et al. Methylmalonate administration decreases Na+,K+-ATPase activity in cerebral cortex of rats. NeuroReport. 2000 Jul 14;11(10):2331-2334.
| Cell experiment [1]: | |
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Cell lines |
SH-SY5Y cells (human neuroblastoma cell line) |
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Preparation Method |
SH-SY5Y cells were maintained in DMEM supplemented with 10% FBS and 1% P/S at 37°C. SH-SY5Y cells were treated with Methylmalonate at pathological concentrations (0.5, 1, 2 and 5mM) for 7 days without media change, followed by assessment of intracellular CoQ10 status via HPLC, MRC complex II-III activity and citrate synthase activity spectrophotometrically, cell viability via MTT assay, and mitochondrial membrane potential via JC-1 flow cytometry. |
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Reaction Conditions |
0.5-5mM; 7 days |
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Applications |
Methylmalonate reduced neuronal CoQ10 status by ~75% at all tested concentrations, decreased MRC complex II-III activity, and had no significant effect on mitochondrial membrane potential or citrate synthase activity. |
| Animal experiment [2]: | |
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Animal models |
30-day-old male Wistar rats |
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Preparation Method |
Rats received three intraperitoneal injections of Methylmalonate (first dose 10μmol/g, followed by two doses 5μmol/g body weight, 90min intervals, pH 7.4) or bilateral intracerebroventricular injection of 2μL 8M Methylmalonate (16μmol) into cerebral ventricles; rats were euthanized 60min after last i.p. injection or 30min after i.c.v. injection, and cerebral cortex and striatum were dissected for measurement of GSH levels, antioxidant enzyme activities (SOD, CAT, GPx, GST, GR, G6PDH), citric acid cycle enzyme activities (CS, IDH, SDH, MDH), glial markers (GFAP, vimentin, GLUT1, IBA1, synaptophysin, KIR4.1) by Western blot, and amino acid levels by LC-MS/MS. |
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Dosage form |
10μmol/g+5μmol/g+5μmol/g; i.p.; three injections 16μmol; i.c.v.; single injection |
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Applications |
Methylmalonate decreased reduced glutathione levels, altered SOD, CAT, GPx, GST activities, inhibited SDH activity in cortex and striatum and CS, IDH, MDH activities in striatum, increased GFAP and GLUT1 levels (i.p.) or GFAP and IBA1 levels (i.c.v.) in striatum, and increased glutamate, glycine, serine levels and decreased tyrosine level in striatum. |
References: [1] Proctor EC, Turton N, Boan EJ, et al. The Effect of Methylmalonic Acid Treatment on Human Neuronal Cell Coenzyme Q10 Status and Mitochondrial Function. Int J Mol Sci. 2020 Nov;21(23):9137. [2] Silveira JA, Marcuzzo MB, Gayger-Dias V, et al. Antioxidant System Disturbances, Bioenergetic Disruption, and Glial Reactivity Induced by Methylmalonic Acid in the Developing Rat Brain. Neuroglia. 2025 Jun;6(3):25. | |
| Cas No. | 516-05-2 | SDF | |
| المرادفات | Isosuccinic Acid, Methylmalonate, MMA, NSC 25201 | ||
| Chemical Name | 2-methylmalonic acid | ||
| Canonical SMILES | OC(C(C(O)=O)C)=O | ||
| Formula | C4H6O4 | M.Wt | 118.09 |
| الذوبان | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 25 mg/ml,PBS (pH 7.2): 10 mg/ml | Storage | Store at -20°C |
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 8.4681 mL | 42.3406 mL | 84.6812 mL |
| 5 mM | 1.6936 mL | 8.4681 mL | 16.9362 mL |
| 10 mM | 846.8 μL | 4.2341 mL | 8.4681 mL |
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 9 reference(s) in Google Scholar.)