| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| Other Sizes |
Purity: =99.38%
| Targets |
3-Methylglutaconic acid does not have a specific pharmacological target but is a pathologically relevant metabolite. It compromises mitochondrial function, elicits reactive species production, and inhibits Na+,K+-ATPase activity. The compound induces oxidative stress in the cerebral cortex.
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| ln Vitro |
In the rat cerebral cortex supernatant, 3-methylglutaconic acid (0.1–5.0 mM, 1 hour) causes lipid oxidative damage; at a concentration of 5 mM, antioxidants (TRO, MEL, SOD + CAT) inhibit lipid oxidation. The process of oxidation[1]. 3-In rat cerebral cortex supernatants, methylglutaconic acid (0.1–5.0 mM, 1 hour) causes protein oxidative damage and lowers non-enzymatic antioxidant defenses [1].
In cell-free systems, 3-Methylglutaconic acid induces lipid and protein oxidative damage. It decreases non-enzymatic antioxidant defenses. The compound reduces mitochondrial redox potential by 25% as determined by resazurin reduction. It inhibits Na+,K+-ATPase activity by 30%. Cellular studies demonstrate that 3-Methylglutaconic acid compromises mitochondrial function in brain cortex cells. The compound elicits reactive species production and inhibits Na+,K+-ATPase activity. These effects lead to oxidative stress and mitochondrial dysfunction in neural cells. |
| ln Vivo |
In vivo, 3-Methylglutaconic acid is a metabolite that accumulates in tissues and is excreted in urine in patients with 3-methylglutaconic aciduria. The compound's accumulation leads to tissue damage through oxidative stress mechanisms. Animal models of MGTA are used to study the pathophysiology of this disorder.
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| Enzyme Assay |
Biochemical assays for 3-Methylglutaconic acid are performed using cell-free systems to measure oxidative damage. Lipid peroxidation assays, protein carbonylation assays, and antioxidant capacity measurements are used. Mitochondrial function is assessed using resazurin reduction assays. Na+,K+-ATPase activity is measured by phosphate release assays.
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| Cell Assay |
Cellular assays for 3-Methylglutaconic acid are conducted using neuronal cell cultures or brain cortex preparations. Cells are treated with the compound, and markers of oxidative stress are measured. Mitochondrial function is assessed using resazurin reduction or MTT assays. Na+,K+-ATPase activity is measured in cell lysates.
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| Animal Protocol |
Animal/Disease Models: Male SD (Sprague-Dawley) rats and male Hartley guinea-pigs[2]
Doses: 0.16 mL/kg, 90 min Route of Administration: intraperitoneal (ip) injection Experimental Results: Increased initial blood pressure and heart rate in rats followed by vagal bradycardia and hypotension (rat) Developed three patterns of cardiovascular changes (Type 1: a period of sympathetically-mediated hypertension and tachycardia followed by vagal bradycardia; Type 2: Increased arterial pressure and heart rate, but no vagal activation; Type 3: demonstrated no significant cardiovascular changes (Guinea-pigs). Animal/Disease Models: Male Wistar rats[3] Doses: 45mg/kg for single dose, 4days Route of Administration: intraperitoneal (ip) injection Experimental Results: diminished in NR2B expression on the whole cerebellum tissue and Purkinje cells. |
| ADME/Pharmacokinetics |
3-Methylglutaconic acid is an endogenous metabolite and its pharmacokinetics are related to metabolic pathways. In patients with MGTA, the compound accumulates in tissues and is excreted in urine. The compound's levels are used as a diagnostic biomarker for MGTA.
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| Toxicity/Toxicokinetics |
Toxicity Summary
Accumulation of 3-methylglutaric acid in the body has been proven toxic. 3-Methylglutaryl-CoA hydratase is involved in the metabolism of 3-methylglutaric acid. Patients lacking this enzyme will accumulate 3-methylglutaric acid in their bodies, resulting in high levels of 3-methylglutaric acid in their urine. (Wikipedia) 3-Methylglutaconic acid is a toxic metabolite that induces oxidative stress and mitochondrial dysfunction. When present in sufficiently high levels, it can act as an acidogen and metabotoxin, inducing acidosis with adverse effects on multiple organ systems. |
| References |
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| Additional Infomation |
3-Methylglutaric acid is a methyl branched-chain fatty acid. It is an intermediate (in the form of coenzyme A thioester) in the leucine degradation pathway and the mevalonate bypass pathway (connecting isoprene metabolism and mitochondrial acetyl-CoA metabolism). 3-Methylglutaryl-CoA hydratase is involved in the metabolism of 3-methylglutaric acid. Deficiency of this enzyme leads to the accumulation of 3-methylglutaric acid in the body, resulting in high levels of 3-methylglutaric acid in the urine. (A3360)
3-Methylglutaconic acid is a diagnostic biomarker for 3-methylglutaconic aciduria (MGTA). The compound's ability to induce oxidative stress makes it relevant for understanding the pathophysiology of this disorder. Research on this compound contributes to understanding mitochondrial diseases and metabolic disorders. |
| Molecular Formula |
C6H8O4
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|---|---|
| Molecular Weight |
144.13
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| Exact Mass |
144.042
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| CAS # |
5746-90-7
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| Related CAS # |
3-Methylglutaconic acid-13C3;1255644-45-1
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| PubChem CID |
1551553
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| Appearance |
White to light yellow solid powder
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| Density |
1.307g/cm3
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| Boiling Point |
399.4ºC at 760mmHg
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| Melting Point |
101 - 105°C (lit.)
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| Flash Point |
209.5ºC
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| Index of Refraction |
1.508
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| LogP |
0.492
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
10
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| Complexity |
180
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C/C(=C\C(=O)O)/CC(=O)O
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| InChi Key |
WKRBKYFIJPGYQC-DUXPYHPUSA-N
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| InChi Code |
InChI=1S/C6H8O4/c1-4(2-5(7)8)3-6(9)10/h2H,3H2,1H3,(H,7,8)(H,9,10)/b4-2+
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| Chemical Name |
(E)-3-methylpent-2-enedioic 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)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 6.9382 mL | 34.6909 mL | 69.3818 mL | |
| 5 mM | 1.3876 mL | 6.9382 mL | 13.8764 mL | |
| 10 mM | 0.6938 mL | 3.4691 mL | 6.9382 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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