| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
2-Methylcitric acid targets glutamate dehydrogenase (GDH), inhibiting its activity at concentrations as low as 0.5 mM. The inhibition is competitive with respect to glutamate. By inhibiting GDH, the compound disrupts glutamate metabolism and interferes with mitochondrial function. It also acts on mitochondria to induce permeability transition and decrease ATP production.
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| ln Vitro |
2-Methylcitric acid (Methylcitric acid) changes the permeability of brain mitochondria and hinders glutamate metabolism. 2-At as little as 0.5 mM, methylcitric acid decreases the action of glutamate dehydrogenase (GDH) [1]. 2-When Ca2+-loaded mitochondria are sustained by various substrates, methylcitric acid (1-3 mM; 150 sec) significantly reduces the potential of the mitochondrial membrane and produces swelling [1]. 2. Methamate dehydrogenase activity is inhibited and permeability transition is induced by methylcitric acid, a strong inhibitor of glutamate oxidation that upsets mitochondrial energy homeostasis. 2. The glutamate transport in mitochondria is not appreciably hampered by methylcitric acid. 2. In liver mitochondria, methylcitric acid has no discernible effect on glutamate mitochondrial transport [1].
In vitro, 2-methylcitric acid inhibits glutamate dehydrogenase (GDH) activity at concentrations as low as 0.5 mM. At concentrations of 1-3 mM, it causes a significant decrease in mitochondrial membrane potential and induces mitochondrial swelling. The compound acts as a potent inhibitor of glutamate oxidation and a permeability transition inducer, disrupting mitochondrial energy homeostasis. Notably, it does not significantly affect glutamate transport function in liver mitochondria. |
| ln Vivo |
In vivo, 2-methylcitric acid accumulates in patients with methylmalonic acidemia and propionic acidemia, serving as a key diagnostic metabolic marker. The compound's accumulation contributes to the mitochondrial dysfunction observed in these disorders. It is used in animal models of organic acidemias to study the pathophysiology of these conditions and to evaluate potential therapeutic interventions.
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| Enzyme Assay |
The in vitro enzyme inhibition assay for 2-methylcitric acid measures its ability to inhibit glutamate dehydrogenase (GDH) activity. The assay is performed using purified GDH enzyme, with glutamate as substrate and NAD+ or NADP+ as cofactor. The reaction is monitored spectrophotometrically by measuring the reduction of NAD(P)+ to NAD(P)H at 340 nm. The compound's inhibitory activity is assessed at various concentrations, and IC50 values are calculated from dose-response curves.
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| Cell Assay |
In vitro cellular studies are conducted using isolated mitochondria or neuronal cell cultures. Mitochondria are treated with 2-methylcitric acid at concentrations ranging from 0.5-3 mM, and mitochondrial function is assessed by measuring membrane potential, oxygen consumption, ATP production, and swelling. In neuronal cells, the compound's effects on glutamate metabolism, oxidative stress, and cell viability are evaluated to model the pathophysiology of organic acidemias.
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| Animal Protocol |
In vivo animal experiments are performed in rodent models of methylmalonic acidemia or propionic acidemia. Animals are administered 2-methylcitric acid via injection or dietary supplementation to elevate tissue levels. Endpoints include assessment of mitochondrial function in brain and liver tissues, measurement of ATP levels, evaluation of oxidative stress markers, and behavioral or neurological assessments to model the central nervous system manifestations of these disorders.
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| ADME/Pharmacokinetics |
2-Methylcitric acid has a molecular formula of C7H10O7 and a molecular weight of 206.15 g/mol. It is soluble in DMSO and water at 80 mg/mL. The compound has a density of 1.178 g/cm³. For storage, powder should be kept at -20°C for up to 3 years, and solutions at -80°C for 1 year. For in vivo formulation, a mixture of 10% DMSO, 40% PEG300, 5% Tween 80, and 45% saline can be used.
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| Toxicity/Toxicokinetics |
As a metabolic intermediate that accumulates in organic acidemias, 2-methylcitric acid is not a therapeutic drug but a research tool. Its toxicity is related to its role in mitochondrial dysfunction. The compound is for research use only and not intended for human therapeutic applications. Standard laboratory safety precautions should be followed when handling it. No significant acute toxicity has been reported at concentrations used in in vitro studies.
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| References | |
| Additional Infomation |
2-Methylcitric acid is a tricarboxylic acid whose function is related to citric acid; it is the conjugate acid of 2-methylcitric acid (3-). Methylcitric acid is a metabolite found or produced in Escherichia coli (K12 strain, MG1655 strain). 2-Methylcitric acid has also been reported to be present in fruit flies, spotted maggots, and other organisms with relevant data.
2-Methylcitric acid is also known as Methylcitric acid. It is primarily used as a research compound to study mitochondrial metabolism, organic acidemias, and the role of glutamate dehydrogenase in energy homeostasis. The compound is supplied as a powder with ≥97% purity. It is not a drug and has no clinical indications or approved therapeutic uses. |
| Molecular Formula |
C7H10O7
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|---|---|
| Molecular Weight |
206.1501
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| Exact Mass |
206.043
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| CAS # |
6061-96-7
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| PubChem CID |
515
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| Appearance |
White to off-white solid powder
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| Density |
1.178g/cm3
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| Boiling Point |
464.4ºC at 760 mmHg
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| Melting Point |
79°C (lit.)
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| Flash Point |
234.7ºC
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| Index of Refraction |
1.586
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| LogP |
-1.4
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
14
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| Complexity |
271
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C(=O)O)C(CC(=O)O)(C(=O)O)O
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| InChi Key |
YNOXCRMFGMSKIJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C7H10O7/c1-3(5(10)11)7(14,6(12)13)2-4(8)9/h3,14H,2H2,1H3,(H,8,9)(H,10,11)(H,12,13)
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| Chemical Name |
2-hydroxybutane-1,2,3-tricarboxylic 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~485.08 mM)
H2O : ~100 mg/mL (~485.08 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (12.13 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 (12.13 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 (12.13 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 (485.08 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 | 4.8508 mL | 24.2542 mL | 48.5084 mL | |
| 5 mM | 0.9702 mL | 4.8508 mL | 9.7017 mL | |
| 10 mM | 0.4851 mL | 2.4254 mL | 4.8508 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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