| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| Other Sizes |
| Targets |
Glutaryl coenzyme A lithium is not a drug and does not target a receptor; it is a substrate for several metabolic enzymes. Specifically, it is a substrate for glutaryl-CoA dehydrogenase (GCDH), which catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA in the degradation pathway of lysine and tryptophan. It also serves as a substrate for acyl-CoA transferases and acyl-CoA thioesterases. Its primary biological role is as a metabolic intermediate, and its accumulation is associated with glutaric acidemia type I, a rare metabolic disorder.
|
|---|---|
| ln Vitro |
In vitro, glutaryl coenzyme A lithium is used as a substrate in enzymatic assays to measure the activity of glutaryl-CoA dehydrogenase (GCDH). In a standard GCDH assay, the enzyme is incubated with 50-100 uM glutaryl-CoA in the presence of electron transfer flavoprotein (ETF) or an artificial electron acceptor such as phenazine methosulfate (PMS) and 2,6-dichlorophenolindophenol (DCPIP). The reduction of DCPIP is measured spectrophotometrically at 600 nm. Glutaryl-CoA is also used to study the specificity of acyl-CoA transferases and to investigate the metabolic consequences of its accumulation in cellular models of glutaric aciduria.
|
| ln Vivo |
In vivo, glutaryl coenzyme A lithium is used in preclinical models to study glutaric acidemia type I (GA1), a rare inborn error of metabolism caused by deficiency of glutaryl-CoA dehydrogenase. Administration of glutaryl-CoA (or its precursor, glutaric acid) to animal models can reproduce the biochemical and pathological features of GA1, including the accumulation of neurotoxic metabolites and the development of striatal lesions. These studies help elucidate disease mechanisms and test therapeutic strategies such as enzyme replacement, gene therapy, or dietary interventions. However, the compound itself is not a therapeutic drug.
|
| Enzyme Assay |
For non-cell-based enzyme assays, the activity of glutaryl-CoA dehydrogenase (GCDH) is measured using a standard spectrophotometric assay. Recombinant human GCDH (10 ug) is pre-incubated in 100 mM Tris-HCl (pH 8.0), 10% glycerol, 1 mM FAD, and varying concentrations of glutaryl coenzyme A lithium (1-100 uM) for 5 min at 30degC. The reaction is initiated by adding 0.5 mM PMS and 0.1 mM DCPIP. The reduction of DCPIP is monitored at 600 nm (ε = 21 mM-¹cm-¹) for 5-10 min. The specific activity is calculated, and kinetic parameters (Km, Vmax) are determined from Lineweaver-Burk plots. Alternatively, a radiolabeled assay using [3H]-glutaryl-CoA can be performed.
|
| Cell Assay |
For in vitro cell-based assays, human fibroblasts or lymphoblasts from patients with glutaric acidemia type I (GA1) are cultured in DMEM supplemented with 10% FBS. Cells are seeded in 6-well plates at 1 × 10⁶ cells/well. To induce accumulation of glutaryl-CoA, cells can be cultured in medium supplemented with excess lysine and tryptophan. Alternatively, glutaryl-CoA is delivered via liposomes or electroporation due to its membrane impermeability. After 24-72 hours, cells are harvested, and acyl-CoAs are extracted with methanol/acetonitrile. Glutaryl-CoA and other acyl-CoA species are quantified by LC-MS/MS. Cellular viability is measured by MTT assay, and markers of oxidative stress and mitochondrial dysfunction are assessed.
|
| Animal Protocol |
For in vivo animal studies, a mouse model of glutaric acidemia type I (GCDH knockout mice) can be used. To mimic metabolic decompensation, mice are administered high doses of lysine (e.g., 10 mmol/kg body weight) by intraperitoneal injection. Glutaryl coenzyme A lithium is not typically injected directly due to its poor cell permeability; instead, glutaric acid or lysine loading is used. However, for acute studies, glutaryl-CoA (10-50 mg/kg) can be administered via tail vein injection in a lipid-based formulation to enhance delivery. Mice are monitored for neurological symptoms, body weight, and survival. At study endpoint, brain and liver tissues are harvested for acyl-CoA analysis by LC-MS/MS, and histological examination is performed to assess neurodegeneration.
|
| ADME/Pharmacokinetics |
Glutaryl coenzyme A lithium has a molecular weight of 887.6 g/mol (free acid) and is highly polar and negatively charged, making it membrane-impermeable. It is soluble in water (10-50 mg/mL) and in 5% acetonitrile in water. The lithium salt form improves solubility and stability. Stock solutions (10 mM) are prepared in 1 mM sodium citrate buffer (pH 5.0) or in water adjusted to pH 5-6 with HCl. The compound is stable at -20degC for up to 6 months but undergoes hydrolysis at neutral to alkaline pH. For enzyme assays, working solutions are prepared fresh and kept on ice. The compound should be stored desiccated and protected from light.
|
| Toxicity/Toxicokinetics |
As a biochemical reagent, glutaryl coenzyme A lithium is not intended for human use. No specific toxicology data is available, but high concentrations of glutaryl-CoA can be neurotoxic by inhibiting mitochondrial enzymes, including succinate dehydrogenase and 2-oxoglutarate dehydrogenase. In animal models, the accumulation of glutaryl-CoA and its derivatives leads to excitotoxicity, oxidative stress, and energy failure. However, at the concentrations used for in vitro enzyme assays (1-100 uM), the compound is generally considered safe to handle. Standard chemical safety precautions (gloves, lab coat, safety glasses) should be used.
|
| Additional Infomation |
Glutaryl-CoA is an ω-carboxyl-CoA formed by the condensation of the sulfhydryl group of coenzyme A with the carboxyl group of glutaric acid. It is a mouse metabolite functionally related to coenzyme A and is the conjugate acid of glutaryl-CoA(5-). Glutaryl-CoA is found in or produced by Escherichia coli (K12 strain, MG1655 strain). There are reports and relevant data regarding the presence of glutaryl-CoA in the human body.
Glutaryl coenzyme A lithium is a research reagent and is not a pharmaceutical drug. It is used as an analytical standard for LC-MS/MS quantification of acyl-CoAs in metabolic research and for the diagnosis of inborn errors of metabolism such as glutaric acidemia type I (GA1). In GA1, deficiency of glutaryl-CoA dehydrogenase leads to accumulation of glutaryl-CoA, glutaric acid, and 3-hydroxyglutaric acid, which are neurotoxic and cause striatal degeneration. This compound is also used to study the regulation of fatty acid beta-oxidation and branched-chain amino acid catabolism. It is for research use only and has no clinical approval status. |
| Molecular Formula |
C26H41LIN7O19P3S
|
|---|---|
| Molecular Weight |
887.57
|
| Exact Mass |
887.155
|
| CAS # |
103192-48-9
|
| PubChem CID |
3081383
|
| Appearance |
White to off-white solid powder
|
| Density |
1.88g/cm3
|
| Index of Refraction |
1.71
|
| LogP |
-5.8
|
| Hydrogen Bond Donor Count |
10
|
| Hydrogen Bond Acceptor Count |
24
|
| Rotatable Bond Count |
24
|
| Heavy Atom Count |
56
|
| Complexity |
1530
|
| Defined Atom Stereocenter Count |
5
|
| SMILES |
CC(C)(COP(=O)(O)OP(=O)(O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N2C=NC3=C(N=CN=C32)N)O)OP(=O)(O)O)C(C(=O)NCCC(=O)NCCSC(=O)CCCC(=O)O)O
|
| InChi Key |
SYKWLIJQEHRDNH-KRPIADGTSA-N
|
| InChi Code |
InChI=1S/C26H42N7O19P3S/c1-26(2,21(39)24(40)29-7-6-15(34)28-8-9-56-17(37)5-3-4-16(35)36)11-49-55(46,47)52-54(44,45)48-10-14-20(51-53(41,42)43)19(38)25(50-14)33-13-32-18-22(27)30-12-31-23(18)33/h12-14,19-21,25,38-39H,3-11H2,1-2H3,(H,28,34)(H,29,40)(H,35,36)(H,44,45)(H,46,47)(H2,27,30,31)(H2,41,42,43)/t14-,19-,20-,21?,25-/m1/s1
|
| Chemical Name |
5-[2-[3-[[4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]ethylsulfanyl]-5-oxopentanoic acid
|
| HS Tariff Code |
2934.99.9001
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1267 mL | 5.6334 mL | 11.2667 mL | |
| 5 mM | 0.2253 mL | 1.1267 mL | 2.2533 mL | |
| 10 mM | 0.1127 mL | 0.5633 mL | 1.1267 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
