| Size | Price | Stock | Qty |
|---|---|---|---|
| 5g |
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| Targets |
Methylmalonate (MMA) is an intermediate metabolite in the vitamin B12-dependent metabolic pathway, primarily associated with the enzyme methylmalonyl-CoA mutase (MCM). It does not act as a "drug" with direct binding targets; instead, its accumulation indicates impaired MCM activity due to vitamin B12 deficiency[1]
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|---|---|
| ln Vitro |
In order to convert methylmalonic acid to succinyl-CoA and, when combined with folate, to convert homocysteine (HC) to methionine, vitamin B-12 is needed. As a result, methyl malonate is much more specific than HC for vitamin B-12 insufficiency [1].
1. In plasma samples from cancer patients (colorectal cancer, breast cancer, lung cancer), Methylmalonate concentrations were measured via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The median plasma Methylmalonate level in vitamin B12-deficient cancer patients was 3.2 μmol/L (range: 1.8–6.5 μmol/L), significantly higher than that in vitamin B12-sufficient cancer patients (median: 0.8 μmol/L, range: 0.4–1.5 μmol/L) and healthy controls (median: 0.7 μmol/L, range: 0.3–1.3 μmol/L) [1] 2. In serum samples, Methylmalonate showed high specificity (92%) and sensitivity (88%) for diagnosing vitamin B12 deficiency in cancer patients, when using a cutoff value of 1.5 μmol/L [1] |
| Enzyme Assay |
1. Plasma/serum sample preparation: Collect 5 mL of venous blood, centrifuge at 3000×g for 10 minutes to separate plasma/serum. Add 100 μL of plasma/serum to 400 μL of ice-cold methanol to precipitate proteins, vortex for 1 minute, and centrifuge at 12,000×g for 15 minutes at 4°C. Collect the supernatant and evaporate to dryness under nitrogen gas [1]
2. LC-MS/MS detection: Reconstitute the dried residue in 100 μL of 0.1% formic acid in water. Inject 10 μL of the reconstituted solution into an LC-MS/MS system equipped with a C18 column. The mobile phase consists of 0.1% formic acid in water (phase A) and 0.1% formic acid in acetonitrile (phase B), with a gradient elution (0–5 minutes: 5% B; 5–10 minutes: 95% B; 10–15 minutes: 5% B). Detect Methylmalonate via multiple reaction monitoring (MRM) with m/z transition 117.0 → 73.0, and quantify using a standard curve (0.1–10 μmol/L Methylmalonate standard) [1] |
| ADME/Pharmacokinetics |
1. Metabolism: Methyl malonate is endogenously produced from propionyl-CoA via propionyl-CoA carboxylase and methylmalonyl-CoA racemicase. Under normal vitamin B12 conditions, methyl malonate is converted to succinyl-CoA via methylmalonyl-CoA mutase (MCM) and enters the tricarboxylic acid cycle; vitamin B12 deficiency blocks this conversion, leading to the accumulation of methyl malonate [1]
2. Distribution: Methyl malonate is distributed in extracellular fluids (plasma, serum, urine), with a plasma to urine concentration ratio of approximately 1:5 (median urine concentration in healthy control group: 4.0 μmol/L) [1] 3. Excretion: Methyl malonate is mainly excreted in urine; 60-70% of the endogenously produced methylmalonic acid in healthy individuals is excreted in 24-hour urine [1] |
| Toxicity/Toxicokinetics |
Toxicity Summary
Methylmalonic acid is an important intermediate in fat and protein metabolism. Abnormal methylmalonic acid metabolism leads to methylmalonic aciduria. This metabolic disorder is attributed to the impaired enzymatic conversion of methylmalonyl-CoA to succinyl-CoA. Accumulation of methylmalonic acid in the body has been shown to be toxic. 1. In cancer patients with severe vitamin B12 deficiency (plasma methylmalonic acid >5 μmol/L), 35% experienced mild neurotoxic symptoms (peripheral numbness, fatigue), which subsided after 8 weeks of vitamin B12 supplementation (plasma methylmalonic acid decreased to <1.5 μmol/L) [1] 2. No direct toxicity of methylmalonic acid was observed in individuals with adequate vitamin B12; the plasma protein binding rate of methylmalonic acid was <10% [1] |
| References | |
| Additional Infomation |
Methylmalonic acid (MMA) is a dicarboxylic acid, formed by replacing a methylene hydrogen atom in the malonic acid molecule with a methyl group. It is a human metabolite functionally related to malonic acid and is the conjugate acid of methylmalonic acid (1-). MMA has been reported in Arabidopsis thaliana, humans, and other organisms with relevant data. MMA is a derivative of malonic acid and an important intermediate in fat and protein metabolism. Abnormal methylmalonic acid metabolism leads to methylmalonic aciduria. This metabolic disorder is caused by impaired enzymatic conversion of methylmalonyl-CoA to succinyl-CoA. MMA is a metabolite found or produced in Saccharomyces cerevisiae. MMA is a derivative of malonic acid and an important intermediate in fat and protein metabolism. Abnormal methylmalonic acid metabolism leads to methylmalonic aciduria. This metabolic disorder is attributed to impaired enzymatic conversion of methylmalonyl-CoA to succinyl-CoA.
1. Methylmalonic acid is a reliable biochemical indicator of vitamin B12 deficiency in cancer patients because cancer-related factors (such as malabsorption and vitamin B12 depletion caused by chemotherapy) often mask the clinical symptoms of vitamin B12 deficiency. Therefore, detecting methylmalonic acid is crucial for early intervention [1]. 2. Unlike homocysteine (another indicator of vitamin B12 deficiency), methylmalonic acid specifically reflects vitamin B12 deficiency (homocysteine may also be elevated due to folic acid deficiency), thus providing a more accurate diagnosis of vitamin B12 deficiency in cancer patients [1]. 3. Clinical application: Monitoring plasma methylmalonic acid levels in cancer patients undergoing chemotherapy helps guide vitamin B12 supplementation and reduces the risk of vitamin B12 deficiency-related complications (e.g., neurotoxicity, anemia) [1]. |
| Molecular Formula |
C4H6O4
|
|---|---|
| Molecular Weight |
118.08804
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| Exact Mass |
118.026
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| CAS # |
516-05-2
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| PubChem CID |
487
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| Appearance |
White to off-white solid powder
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| Density |
1.45
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| Boiling Point |
334.4±25.0 °C at 760 mmHg
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| Melting Point |
129-136 ºC
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| Flash Point |
170.2±19.7 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.474
|
| LogP |
-0.21
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
|
| Heavy Atom Count |
8
|
| Complexity |
103
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ZIYVHBGGAOATLY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C4H6O4/c1-2(3(5)6)4(7)8/h2H,1H3,(H,5,6)(H,7,8)
|
| Chemical Name |
2-methylpropanedioic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~846.81 mM)
H2O : ~100 mg/mL (~846.81 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (21.17 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (21.17 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (21.17 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (846.81 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 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 | 0.8468 mL | 4.2341 mL | 8.4681 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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