Acetyl-CoA trilithium primarily targets acetylation-related enzymes and metabolic pathways within cells. Its targets include histone acetyltransferases, carnitine acetyltransferase, and citrate synthase. Furthermore, by modulating Acetyl-CoA levels, it affects the activity of autophagy-related proteins (e.g., LC3) and the acetyltransferase EP300; Endogenous Metabolite

In vitro, Acetyl-CoA trilithium maintains acetylation reactions in cell-free systems by donating acetyl groups. In cellular models (e.g., starved U2OS cells), supplementation with Acetyl-CoA trilithium significantly increases cytoplasmic protein acetylation levels and reduces starvation-induced autophagic flux, highlighting its central role in nutrient sensing and autophagy regulation.

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In starved U2OS cells, lithium acetyl-CoA promotes cytoplasmic protein acetylation while decreasing starvation-induced autophagy flux. (U2OS cells were microinjected with lithium acetyl-CoA, stably expressing GFP-LC3, cultured in the absence of nutrients with 100 nM BafA1, and frozen after three hours) [2].

In vivo studies demonstrate that in a mouse cardiac pressure overload model, Acetyl-CoA trilithium alleviates pressure overload-induced cardiomyopathy by suppressing maladaptive autophagy. Additionally, during starvation, endogenous Acetyl-CoA levels significantly decrease in the heart and muscles of mice, and supplementation with this compound helps maintain metabolic homeostasis.

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In a mouse cardiac pressure overload model, lithium acetyl-CoA reduces pressure overload-induced cardiomyopathy by blocking maladaptive autophagy [2][3]. For a full day, mice that were fed nothing but had unlimited access to water demonstrated marked decreases in the levels of total acetyl-CoA lithium in various organs, such as the muscle and heart. These reductions were correlated with decreased levels of protein acetylation. The same experimental setup, however, increased liver acetyl-CoA lithium and protein acetylation levels while having no discernible impact on brain acetyl-CoA lithium concentrations [4].

Acetyl-CoA trilithium is used as a substrate for acetyltransferase activity assays in cell-free systems. A typical protocol involves incubating the purified target enzyme, Acetyl-CoA trilithium, and the specific substrate (e.g., histones or peptides) in a Tris-HCl buffer (pH 7.5). After the reaction, free CoA production is measured using DTNB or a fluorescent probe (e.g., MMBC) to calculate enzyme activity.

In cellular assays, Acetyl-CoA trilithium is typically administered via microinjection or in permeabilized cell models due to its membrane-impermeable nature. For example, in starved U2OS cells, the compound is microinjected, and cells are cultured in medium containing BafA1 for 3 hours. Autophagic flux is then assessed by Western Blot for LC3-II levels or by fluorescence microscopy for GFP-LC3 puncta.

In animal models, Acetyl-CoA trilithium is typically administered via intraperitoneal or intravenous injection. In a mouse cardiac hypertrophy model, pressure overload is induced by transverse aortic constriction (TAC), followed by daily treatment with Acetyl-CoA trilithium. At the endpoint, cardiac function is assessed by echocardiography, and tissues are collected for histological analysis (e.g., H&E and Masson staining) and autophagy marker detection.

Specific pharmacokinetic data (e.g., half-life, bioavailability) for Acetyl-CoA trilithium are limited in public literature. As an endogenous metabolite, it is widely distributed in the body but is unstable in plasma and susceptible to metabolism by esterases. Its tissue concentration is tightly regulated by the cellular metabolic state, and exogenous administration faces challenges in directly increasing intracellular concentration without specific delivery systems or microinjection.

According to available Material Safety Data Sheets, Acetyl coenzyme A trilithium is generally classified as a non-hazardous substance or mixture under normal laboratory handling conditions. Detailed toxicological data for this compound is lacking, but suppliers warn it is for research use only and not for human or veterinary use. It is recommended to wash immediately after skin contact or inhalation, and it is presumed to be slightly irritating at high concentrations.

[1]. The growing landscape of lysine acetylation links metabolism and cell signalling. Nat Rev Mol Cell Biol. 2014 Aug;15(8):536-50.

[2]. Regulation of autophagy by cytosolic acetyl-coenzyme A. Mol Cell. 2014 Mar 6;53(5):710-25.

[3]. Cardiac autophagy is a maladaptive response to hemodynamic stress. J Clin Invest. 2007 Jul;117(7):1782-93.

[4]. Acetyl coenzyme A: a central metabolite and second messenger. Cell Metab. 2015 Jun 2;21(6):805-21.

Acetyl-CoA is involved in the biosynthesis of fatty acids and sterols, fatty acid oxidation, and the metabolism of various amino acids. It also functions as a biological acetylation agent. Lysine acetylation is a conserved post-translational modification of proteins that links acetyl-CoA metabolism to cellular signaling. In recent years, mass spectrometry has made significant progress in the identification and quantification of lysine acetylation, deepening our understanding of its role in various biological processes by regulating protein-protein interactions, activity, and localization. Furthermore, proteins frequently undergo other types of acylation modifications, such as formylation, butyrylation, propionylation, succinylation, malonylation, myristylation, glutarylation, and crotonylation. The intricate link between lysine acylation and cellular metabolism has been elucidated through various metabolite-sensitive acylation reactions and their selective removal by sirtuin deacylases. These new findings reveal novel functions of different lysine acylations and deacylases, while also highlighting the mechanisms by which acetylation regulates various cellular processes. [1] Acetyl-CoA (AcCoA) is an important integrator of nutritional status at the intersection of fat, sugar and protein catabolism. This study shows that nutritional deprivation leads to rapid consumption of AcCoA. Consumption of AcCoA results in a corresponding decrease in the overall acetylation level of cytoplasmic proteins and induces autophagy—a self-digestive process that maintains cellular homeostasis. Various manipulations aimed at increasing or decreasing cytoplasmic acetyl-CoA (AcCoA) levels resulted in inhibition or induction of autophagy in cultured human cells and mice, respectively. Furthermore, in a cardiac stress overload model, maintaining high levels of AcCoA inhibited maladaptive autophagy. AcCoA depletion reduced the activity of acetyltransferase EP300, which is essential for the inhibition of autophagy by high levels of AcCoA. In summary, our results demonstrate that cytoplasmic AcCoA plays a role as a core metabolic regulator of autophagy, thus elucidating an AcCoA-centered pharmacological strategy for the therapeutic regulation of autophagy. [2] Cardiac hypertrophy is a major predictor of heart failure and a common disease with high mortality. However, little is known about the mechanisms of transition from stable cardiac hypertrophy to decompensated heart failure. This study investigated the role of autophagy, a conserved pathway that mediates the massive degradation of long-lived proteins and organelles, ultimately leading to cell death. To quantify autophagy activity, we constructed an "autophagy reporter gene" mouse strain and demonstrated that short-term nutrient deprivation can induce cardiomyocyte autophagy in vivo. Pressure load induced by aortic constriction can lead to heart failure and significantly enhance cardiac autophagy. Load-induced autophagy activity peaked at 48 hours and remained significantly elevated for at least 3 weeks. Furthermore, autophagy activity was not spatially uniformly distributed but was particularly pronounced in the basal septa. Heterozygous loss of the gene encoding Beclin 1 (a protein essential for early autophagosome formation) reduced cardiomyocyte autophagy and attenuated pathological remodeling induced by severe stress. Conversely, overexpression of Beclin 1 enhanced autophagy activity and exacerbated pathological remodeling. In summary, these results suggest that autophagy is involved in the pathogenesis of load-induced heart failure and hints at its potential as a target for novel therapeutic interventions. [3] Acetyl-CoA (acetyl-CoA) is an important metabolic intermediate. The abundance of acetyl-CoA in different subcellular compartments reflects the overall energy state of the cell. In addition, the concentration of acetyl-CoA affects the activity or specificity of a variety of enzymes by allosteric regulation or altering substrate availability. Finally, acetyl-CoA controls key cellular processes, including energy metabolism, mitosis, and autophagy, by influencing the acetylation profiles of a variety of proteins, including histones, directly or through epigenetic regulation of gene expression. Thus, acetyl-CoA determines the balance between catabolism and anabolism by acting as both a metabolic intermediate and a second messenger. [4]

C23H35N7O17P3S-3.3[LI+]

827.370100000001

827.15

32140-51-5

Acetyl Coenzyme A trisodium;102029-73-2;Acetyl coenzyme A;72-89-9

146014552

White to off-white solid powder

1.362

9

22

20

52

1380

5

CC(=O)SCCN=C(CCN=C([C@@H](C(C)(C)COP(=O)(O)OP(=O)(O)OC[C@@H]1[C@H]([C@H]([C@H](N2C=NC3=C(N)N=CN=C32)O1)O)OP(=O)(O)[O-])O)[O-])[O-].[Li+].[Li+].[Li+]

MQDBECZUJONFAI-QJBWUGSNSA-N

InChI=1S/C23H38N7O17P3S.Li/c1-12(31)51-7-6-25-14(32)4-5-26-21(35)18(34)23(2,3)9-44-50(41,42)47-49(39,40)43-8-13-17(46-48(36,37)38)16(33)22(45-13)30-11-29-15-19(24)27-10-28-20(15)30;/h10-11,13,16-18,22,33-34H,4-9H2,1-3H3,(H,25,32)(H,26,35)(H,39,40)(H,41,42)(H2,24,27,28)(H2,36,37,38);/t13-,16-,17-,18+,22-;/m1./s1

Acetyl coenzyme A lithium salt; Acetylcoenzyme A, trilithium salt; EINECS 278-233-4; 278-233-4; 631-193-5; Acetyl coenzyme A trilithium salt; 75520-41-1; 32140-51-5;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)