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| Targets |
Malonyl CoA is a well-known inhibitor of carnitine palmitoyltransferase 1 (CPT1), the rate-limiting enzyme for mitochondrial fatty acid oxidation. High concentrations of malonyl-CoA suppress fatty acid oxidation, while low concentrations permit it. This regulation is central to the control of energy homeostasis in the liver, heart, and skeletal muscle. Additionally, malonyl-CoA serves as the two-carbon donor substrate for fatty acid synthase (FASN) in the biosynthesis of long-chain fatty acids. The 13C3-labeled version targets the same metabolic enzymes but acts as a tracer. Because of its role in fatty acid metabolism, malonyl-CoA indirectly affects signaling pathways such as AMPK and mTOR.
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| ln Vitro |
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Studies involving the human use of drugs labeled with deuterium suggest that these compounds may offer some advantages when compared with their nondeuterated counterparts. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs. Deutetrabenazine is the first deuterated drug to receive Food and Drug Administration approval. This deuterated form of the drug tetrabenazine is indicated for the treatment of chorea associated with Huntington's disease as well as tardive dyskinesia. Ongoing clinical trials suggest that a number of other deuterated compounds are being evaluated for the treatment of human diseases and not merely as research tools.
In vitro, Malonyl CoA-13C3 lithium is used as a tracer in enzyme assays for fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). In a FASN assay, the enzyme is incubated with acetyl-CoA, NADPH, and the 13C-labeled malonyl-CoA substrate. After incubation at 37degC for 30-60 minutes, the reaction products (13C-labeled fatty acids, primarily palmitate) are extracted and analyzed by LC-MS. The isotopic labeling allows precise quantification of the reaction rate without interference from endogenous malonyl-CoA. Malonyl-CoA also inhibits CPT1 activity in vitro, as measured using isolated mitochondria or recombinant CPT1 enzyme; the 13C-labeled version is used to study the binding stoichiometry and inhibition kinetics. |
| ln Vivo |
Deuterated compounds may, in some cases, offer advantages over nondeuterated forms, often through alterations in clearance. Deuteration may also redirect metabolic pathways in directions that reduce toxicities. The approval of additional deuterated compounds may soon follow. Clinicians will need to be familiar with the dosing, efficacy, potential side effects, and unique metabolic profiles of these new entities.
In vivo, Malonyl CoA-13C3 lithium is used for metabolic flux analysis. It is typically administered to rodents (mice or rats) via intravenous (IV) injection or intraperitoneal (IP) injection to trace fatty acid synthesis. For example, after injection of 13C3-malonyl-CoA, animals are euthanized at specific time points, and tissues (liver, adipose, heart) are harvested. Lipids are extracted, saponified to release free fatty acids, and analyzed by GC-MS or LC-MS to determine the isotopic enrichment of palmitate and other fatty acids. This allows researchers to quantify the rate of de novo lipogenesis in vivo under different nutritional or disease states. The tracer can also be used to study fatty acid oxidation by measuring 13CO2 production in breath after administering a labeled precursor. |
| Enzyme Assay |
The in vitro enzyme assay using Malonyl CoA-13C3 lithium to study fatty acid synthase (FASN) activity is performed as follows. Prepare a reaction mixture (100 uL) containing 100 mM potassium phosphate buffer (pH 6.5), 1 mM DTT, 0.25 mM NADPH, 30 uM acetyl-CoA, and varying concentrations of malonyl CoA-13C3 lithium (0-100 uM). Add 50 ng of recombinant human FASN enzyme to initiate the reaction. Incubate at 37degC for 30 minutes. Terminate the reaction by adding 100 uL of methanol containing a fatty acid internal standard (e.g., heptadecanoic acid-C17:0). Extract the fatty acids with hexane, derivative them to methyl esters using 14% BF3 in methanol, and analyze by GC-MS in selected ion monitoring (SIM) mode. Monitor ions corresponding to the unlabeled palmitate (m/z 270) and the 13C3-labeled palmitate (m/z 273). The ratio of these signals allows calculation of FASN activity. For CPT1 inhibition assays, use isolated liver mitochondria incubated with [3H]carnitine and palmitoyl-CoA, and the labeled malonyl-CoA acts as the competitive inhibitor.
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| Cell Assay |
Malonyl CoA-13C3 lithium is not used directly in standard cell viability or proliferation assays. Instead, it is added to cell culture medium as a metabolic tracer to study lipid metabolism in vitro. Cells (e.g., primary hepatocytes, HepG2, or 3T3-L1 adipocytes) are seeded in 6-well plates and cultured until 80-90% confluent. The medium is replaced with fresh medium containing 10-50 uM of Malonyl CoA-13C3 lithium (or a stable isotope-labeled precursor like [13C3]glucose that converts to labeled malonyl-CoA intracellularly). The cells are incubated for 2-24 hours at 37degC, 5% CO2. After incubation, cells are washed with cold PBS and harvested by scraping. Lipids are extracted using chloroform/methanol (2:1), and the organic phase is dried under nitrogen. The fatty acids are hydrolyzed and derivatized to methyl esters as described above. The isotopic enrichment of newly synthesized fatty acids is determined by GC-MS, allowing measurement of de novo lipogenesis flux in cells under various treatment conditions (e.g., insulin stimulation or compound treatment).
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| Animal Protocol |
For in vivo metabolic flux studies using Malonyl CoA-13C3 lithium, a typical animal protocol involves male C57BL/6J mice (8-12 weeks old). Mice are fasted overnight (12-16 hours) to deplete glycogen and reduce background unlabeled fatty acids. On the day of the experiment, Malonyl CoA-13C3 lithium is dissolved in sterile saline (or PBS) and administered via intraperitoneal (IP) injection at a dose of 10-20 mg/kg body weight. Alternatively, for continuous labeling, an IV bolus followed by a constant infusion can be performed using an osmotic pump. Blood samples (20-50 uL) are collected from the tail vein at time points 0, 15, 30, 60, 120, and 240 minutes post-injection. At the end of the experiment (e.g., 4-6 hours post-injection), mice are euthanized, and tissues (liver, epididymal white adipose tissue, muscle) are rapidly dissected, snap-frozen in liquid nitrogen, and stored at -80degC. Lipids are extracted from homogenized tissue, and fatty acid methyl esters (FAMEs) are analyzed by GC-MS. The rate of de novo lipogenesis is calculated from the incorporation of 13C into palmitate and other fatty acids.
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| ADME/Pharmacokinetics |
Malonyl CoA-13C3 lithium has a molecular weight of 856.57 g/mol for the malonyl-CoA core, with an additional lithium cation (the exact lithium content varies by batch). The compound is a coenzyme A derivative. When used as a tracer, it is administered at tracer doses (1-20 mg/kg IV or IP) and its pharmacokinetics are not typically measured because it is rapidly metabolized intracellularly. However, the bioavailability of malonyl-CoA is low due to its high polarity and negative charge, which prevent passive diffusion across cell membranes. Consequently, in vivo studies often rely on administration of labeled precursors (e.g., [13C3]glucose or [13C2]acetate) that are taken up by cells and converted endogenously to malonyl-CoA, rather than administering malonyl-CoA directly. Once inside the cell, malonyl-CoA is rapidly turned over with a half-life of minutes, as it is either consumed by FASN or hydrolyzed back to acetyl-CoA by malonyl-CoA decarboxylase (MLYCD).
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| Toxicity/Toxicokinetics |
Malonyl-CoA itself is a normal cellular metabolite and has low intrinsic toxicity at physiological concentrations. The lithium salt form introduces a small amount of lithium ions, which at high doses could cause lithium toxicity (nausea, tremor, polyuria). However, for tracer studies, the mass of lithium administered is negligible (micrograms to low milligrams per kg), well below the therapeutic window for lithium carbonate (e.g., 5-10 mg/kg for bipolar disorder). Malonyl-CoA can inhibit CPT1 and thus reduce fatty acid oxidation if administered at supraphysiological concentrations, potentially causing metabolic dysregulation or hypoglycemia. However, at tracer levels, no toxicity is expected. The compound is for research use only and not for human or clinical use. Standard safety precautions for handling biochemical reagents (gloves, lab coat, safety glasses) should be used. The compound should be stored at -20degC or -80degC to prevent degradation of the CoA thioester bond.
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| References | |
| Additional Infomation |
Malonyl CoA-13C3 lithium is also known as Malonyl-13C3 coenzyme A lithium salt, [13C3]Malonyl coenzyme A lithium, or Malonyl-13C3-CoA lithium. The CAS number is not provided in standard database entries, but the molecular formula is typically written as (13C)3C21H38N7O19P3S•xLi+. The isotopic purity is generally >99 atom% 13C. This compound is an essential tool for metabolic engineering and fluxomics studies to understand lipid metabolism in health and disease, including obesity, diabetes, non-alcoholic fatty liver disease (NAFLD), and cancer. It can be used as an internal standard for quantitative analysis by NMR, GC-MS, or LC-MS. The product should be handled on ice, as the thioester bond is labile to hydrolysis at room temperature.
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| Molecular Formula |
C2113C3H38N7O19P3S
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| Molecular Weight |
856.56
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| Related CAS # |
Malonyl CoA lithium; 108347-84-8
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| Appearance |
Typically exists as solids at room temperature
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| Synonyms |
Malonyl coenzyme A-13C3 lithium
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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 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
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1675 mL | 5.8373 mL | 11.6746 mL | |
| 5 mM | 0.2335 mL | 1.1675 mL | 2.3349 mL | |
| 10 mM | 0.1167 mL | 0.5837 mL | 1.1675 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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