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| Other Sizes |
| Targets |
Human Endogenous Metabolite
Sodium alpha-ketoisocaproate (alpha-KIC) targets multiple metabolic pathways and enzymes. It is a potent stimulator of insulin secretion from pancreatic beta cells, making it a key player in glucose homeostasis. It also acts as an inhibitor of pyruvate transport and may influence the activity of branched-chain amino acid transaminase (BCAT) and branched-chain alpha-keto acid dehydrogenase (BCKDH) complexes. It is also known to inhibit the degradation of branched-chain amino acids by promoting feedback inhibition. Additionally, alpha-KIC can be converted to HMG-CoA, influencing cholesterol synthesis. It serves as a substrate for the enzyme alpha-ketoisocaproate dioxygenase. |
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| ln Vitro |
In vitro, Sodium alpha-ketoisocaproate (alpha-KIC) stimulates insulin secretion in a concentration-dependent manner in isolated pancreatic islets and beta-cell lines (e.g., INS-1, MIN6). At concentrations of 0.5-10 mM, it significantly increases insulin release and cellular ATP content. It also enhances the oxidation of leucine and inhibits its own degradation via feedback inhibition. alpha-KIC (1-10 mM) serves as a substrate for the tricarboxylic acid (TCA) cycle after conversion to acetyl-CoA. It also inhibits pyruvate transport with an IC₅0 in the low millimolar range. The compound is not cytotoxic at concentrations up to 20 mM in most cell types.
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| ln Vivo |
In vivo, Sodium alpha-ketoisocaproate (alpha-KIC) has been studied in animal models for its effects on insulin secretion, glucose homeostasis, and protein metabolism. In rats, oral or intraperitoneal administration (100-500 mg/kg) stimulates insulin secretion and lowers blood glucose levels. In a rat model of diabetes (streptozotocin-induced), alpha-KIC may have beneficial effects on glycemic control. It is also used in studies of branched-chain amino acid metabolism and muscle wasting. In mice, alpha-KIC (200-1000 mg/kg, oral) has been shown to reduce muscle protein breakdown and improve nitrogen balance. It is an endogenous metabolite, and exogenous administration is generally safe and well-tolerated.
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| Enzyme Assay |
The activity of enzymes involved in leucine metabolism (e.g., BCAT, BCKDH) can be measured using Sodium alpha-ketoisocaproate as a substrate. For example, BCKDH activity is measured in isolated mitochondria: mitochondria are incubated with 0.1-1 mM alpha-KIC in assay buffer (50 mM potassium phosphate pH 7.5, 0.5 mM CoA, 1 mM NAD+, 0.1 mM thiamine pyrophosphate, 0.5 mM MgCl2) at 37degC for 10-30 min. The formation of isovaleryl-CoA is coupled to the reduction of NAD+, which is measured at 340 nm. For BCAT, alpha-KIC is the product of transamination, and its formation is measured by HPLC.
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| Cell Assay |
For cellular insulin secretion studies, INS-1 or MIN6 cells are seeded in 24-well plates (2×10⁵ cells/well) and cultured in RPMI-1640 with 10% FBS for 48 h. Cells are pre-incubated in Krebs-Ringer bicarbonate HEPES buffer (KRBH) without glucose for 1 h. They are then treated with Sodium alpha-ketoisocaproate (0.5-20 mM) in KRBH containing 2.8 mM glucose for 1 h. The supernatant is collected, and insulin concentration is measured by ELISA. For cell viability, MTT assays are performed. The stimulation of insulin secretion is concentration-dependent, with maximal effects observed at 5-10 mM alpha-KIC.
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| Animal Protocol |
In vivo insulin secretion and glucose tolerance studies in rodents: Male Sprague-Dawley rats (200-250 g, n=6-10/group) are fasted overnight. Sodium alpha-ketoisocaproate is dissolved in saline and administered orally (100-500 mg/kg) or intraperitoneally (50-200 mg/kg). Blood samples are collected from the tail vein at 0, 15, 30, 60, 90, 120 min post-dose. Insulin levels are measured by ELISA, and glucose levels are measured by glucometer. An oral glucose tolerance test (OGTT) can be performed 30 min after alpha-KIC administration, followed by 2 g/kg glucose orally. alpha-KIC significantly increases insulin secretion and improves glucose tolerance compared to vehicle controls.
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| ADME/Pharmacokinetics |
Sodium alpha-ketoisocaproate (alpha-KIC) is an endogenous metabolite that is rapidly absorbed from the gastrointestinal tract. Following oral administration, peak plasma levels of alpha-KIC are reached within 30-60 minutes. It is transported into cells via monocarboxylate transporters (MCTs). The elimination half-life in rodents is approximately 1-2 hours. alpha-KIC is metabolized in the mitochondria of various tissues (liver, kidney, muscle) via the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex to isovaleryl-CoA, which is further metabolized to acetyl-CoA and acetoacetate. It can also be converted back to leucine via transamination with glutamate, forming alpha-KG. The compound is not protein-bound and is excreted in urine as metabolites.
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| Toxicity/Toxicokinetics |
Sodium alpha-ketoisocaproate has low toxicity. The oral LD₅0 in rats is >5000 mg/kg, indicating high safety. It is an endogenous metabolite, and administration of exogenous alpha-KIC in animal studies (up to 1000 mg/kg) does not cause significant adverse effects. The compound is not mutagenic or genotoxic. It may cause mild gastrointestinal upset at very high doses. It is not a skin or eye irritant. For research use, standard safety precautions for handling laboratory chemicals should be followed: use PPE (gloves, lab coat, goggles), work in a fume hood, avoid inhalation and skin contact.
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| References | |
| Additional Infomation |
Sodium alpha-ketoisocaproate (alpha-KIC) is an endogenous metabolite that serves as a key intermediate in leucine catabolism. It is not an FDA-approved drug, but it is available as a dietary supplement for muscle protein synthesis and athletic performance. In research, it is used to study insulin secretion, branched-chain amino acid metabolism, diabetes, and neurological disorders. It has also been investigated for potential therapeutic use in maple syrup urine disease (MSUD). For research use only, not for diagnostic or therapeutic applications. Storage: powder at -20degC for 3 years, 4degC for 2 years; in solvent at -80degC for 1 year.
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| Molecular Formula |
C6H9NAO3
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|---|---|
| Molecular Weight |
152.12
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| Exact Mass |
152.045
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| CAS # |
4502-00-5
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| Related CAS # |
816-66-0 (Parent)
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| PubChem CID |
4137900
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| Appearance |
White to yellow solid powder
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| Melting Point |
275 °C (dec.)(lit.)
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| LogP |
0
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
10
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| Complexity |
131
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)CC(C([O-])=O)=O.[Na+]
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| InChi Key |
IXFAZKRLPPMQEO-UHFFFAOYSA-M
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| InChi Code |
InChI=1S/C6H10O3.Na/c1-4(2)3-5(7)6(8)9;/h4H,3H2,1-2H3,(H,8,9);/q;+1/p-1
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| Chemical Name |
sodium 4-methyl-2-oxopentanoate
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| Synonyms |
Sodium 4-methyl-2-oxopentanoate; 2-Ketoisocaproic acid sodium salt
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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) |
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 | 6.5738 mL | 32.8688 mL | 65.7376 mL | |
| 5 mM | 1.3148 mL | 6.5738 mL | 13.1475 mL | |
| 10 mM | 0.6574 mL | 3.2869 mL | 6.5738 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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