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| Targets |
The L-enantiomer of glutamic acid (L-glutamic acid) targets two main classes of receptors: ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs). iGluRs are ligand-gated ion channels that mediate fast excitatory neurotransmission and include the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor, the NMDA (N-methyl-D-aspartate) receptor, and the kainate receptor. mGluRs are G-protein-coupled receptors (GPCRs) that modulate synaptic transmission and plasticity through second messenger systems. L-Glutamic acid is the primary excitatory neurotransmitter in the mammalian central nervous system and is involved in learning, memory, synaptic plasticity, and neuronal development. It is also a key intermediate in amino acid metabolism and the citric acid cycle (via conversion to alpha-ketoglutarate). The D-enantiomer (D-glutamic acid) does not bind to glutamate receptors with high affinity but is a component of bacterial cell walls and may activate certain bacterial receptors. DL-Glutamic acid hydrate is used in research to study both enantiomer-specific interactions with receptors and enzymes, including glutamate decarboxylase (GAD, which converts L-glutamate to GABA) and glutamine synthetase (which converts L-glutamate to L-glutamine). The racemic mixture allows for the simultaneous study of both enantiomers.
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| ln Vitro |
In vitro activity of DL-Glutamic acid is typically measured in assays involving ionotropic and metabotropic glutamate receptors. For NMDA receptor activation assays, HEK293 cells expressing the NMDA receptor (NR1/NR2B subunits) and a Ca2+-sensitive fluorescent dye (e.g., Fluo-4 AM, 4 uM) are used. After loading the dye (30 minutes at 37degC), cells are washed and transferred to a fluorescence plate reader. L-Glutamic acid (0.1-1000 uM) in the presence of 10 uM glycine (a co-agonist) and 10 uM NMDA (as a positive control) is added, and the increase in fluorescence (excitation 485 nm, emission 525 nm) is measured. The EC₅0 for L-glutamic acid at the NMDA receptor is approximately 0.5-2 uM. For AMPA receptor activation assays, similar Ca2+ imaging experiments are performed using HEK293 cells expressing the AMPA receptor (GluA1/GluA2). The EC₅0 for L-glutamic acid at the AMPA receptor is approximately 10-100 uM. For mGluR activation (e.g., mGluR1, mGluR5), the accumulation of inositol phosphate (IP) is measured. Cells expressing the receptor are labeled with [3H]-myo-inositol, then stimulated with L-glutamic acid (0.1-1000 uM) in the presence of 10 mM LiCl (to inhibit IP breakdown). The EC₅0 for L-glutamic acid at mGluR1 is approximately 2-10 uM. For glutamate decarboxylase (GAD) activity assays, recombinant GAD65 or GAD67 is incubated with L-glutamic acid (1-100 mM) in 0.1 M potassium phosphate buffer (pH 7.0) containing 0.2 mM pyridoxal phosphate (PLP) at 37degC for 30-60 minutes. The reaction is terminated by adding 100 uL of 0.1 M HCl, and the GABA produced is measured by HPLC with fluorescence detection after derivatization with o-phthalaldehyde (OPA) or by an enzyme-linked assay (GABase). The Km of GAD for L-glutamate is typically 2-10 mM. For the D-enantiomer, D-glutamic acid is not a substrate for GAD. For bacterial enzyme assays, D-glutamic acid is a substrate for D-alanine-D-glutamate ligase and other enzymes involved in peptidoglycan synthesis.
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| Cell Assay |
For in vitro cell-based experiments, DL-Glutamic acid is used to study neuronal excitotoxicity, synaptic transmission, and cellular metabolism. Primary cortical neurons or hippocampal neurons are isolated from embryonic day 18 (E18) rats and cultured in Neurobasal medium with B27 supplement. For excitotoxicity studies, mature neurons (14-21 days in vitro) are treated with L-glutamic acid (10-1000 uM) for 10-30 minutes in the absence of magnesium (Mg2+-free buffer to allow NMDA receptor activation). After treatment, the medium is replaced with conditioned medium, and cells are incubated for 24 hours. Cell viability is measured by the MTT assay or by LDH release. High concentrations of L-glutamate (≥100 uM) cause significant neuronal death (NMDA receptor-mediated excitotoxicity). The DL racemic mixture (100-1000 uM) will also induce excitotoxicity due to the L-enantiomer. For synaptic transmission studies, electrophysiological recordings (patch clamp) are performed on neurons in culture. L-Glutamic acid (1-10 uM) is applied by pressure ejection to measure evoked excitatory postsynaptic currents (EPSCs) or AMPA/NMDA receptor-mediated currents. For metabolic studies, human cell lines such as HepG2 (hepatocytes) are treated with L-glutamic acid (1-10 mM) for 24-48 hours, and the intracellular levels of glutathione (GSH), alpha-ketoglutarate, and ATP are measured by colorimetric assays or LC-MS. L-Glutamic acid supplementation increases intracellular glutathione levels (by 30-50%) and protects against oxidative stress. For differentiation studies, neural stem cells (NSCs) are cultured in the presence of L-glutamic acid (10-100 uM) to promote neuronal differentiation, measured by the expression of beta-tubulin III and MAP2 by immunocytochemistry. D-Glutamic acid (1-10 mM) is used in bacterial culture studies to study peptidoglycan synthesis and bacterial growth.
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| Animal Protocol |
For in vivo animal experiments, L-Glutamic acid is used in models of neurodegeneration, excitotoxicity, and metabolic disorders. Male C57BL/6J mice (20-25 g) or Sprague-Dawley rats (200-250 g) are used. L-Glutamic acid is dissolved in sterile saline or PBS (pH 7.4) and administered by intraperitoneal (IP) injection at doses of 100-1,000 mg/kg, or by intracerebroventricular (ICV) injection (5-20 ug/animal) to bypass the blood-brain barrier. For excitotoxicity models, L-glutamic acid (50-200 nmol) is injected directly into the striatum or hippocampus of rats via stereotaxic injection, and neuronal death is measured by TUNEL staining or by measuring the lesion volume (cresyl violet staining) after 3-7 days. The NMDA antagonist MK-801 (dizocilpine) is used as a positive control to block excitotoxicity. For metabolic studies, animals are administered L-glutamic acid by oral gavage (500-2,000 mg/kg) or IP (250-500 mg/kg). Blood samples are collected at time points 0, 15, 30, 60, 120, and 240 minutes post-dose, and plasma amino acid levels are measured by HPLC or LC-MS/MS. L-Glutamic acid is rapidly cleared from the plasma, with a half-life of approximately 15-30 minutes. For long-term studies, the compound is added to drinking water (0.5-2% w/v) for 4-12 weeks. Body weight, food and water consumption, and behavior are monitored. No significant toxicity is observed at doses up to 1,000 mg/kg/day. For studies of the D-enantiomer, D-glutamic acid (100-1,000 mg/kg) is administered to mice, and its effect on bacterial gut flora, renal function, or neurobehavior is assessed. D-Glutamic acid is largely excreted unchanged in the urine. For pharmacokinetic studies, serial blood samples are collected, and concentrations of L- and D-glutamic acid are measured by chiral HPLC or LC-MS/MS using a chiral column (e.g., Chirobiotic T).
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| ADME/Pharmacokinetics |
The pharmacokinetic (PK) properties of L-Glutamic acid are well characterized. Following oral administration, L-glutamic acid is absorbed from the small intestine via the sodium-dependent neutral amino acid transporter (B0AT1, SLC6A19). However, a significant portion of L-glutamate is metabolized by the intestinal mucosa, which contains glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT), as well as by the liver (first-pass effect). The oral bioavailability of L-glutamic acid is low, estimated to be less than 10%. Peak plasma concentrations (Cmax) are achieved within 30-60 minutes post-dose (Tmax). The elimination half-life (t½) of L-glutamate in the plasma is very short, approximately 5-10 minutes in rodents, due to rapid uptake into cells and metabolism. The volume of distribution (Vd) is large (>2 L/kg), indicating distribution into total body water. Plasma protein binding is low (<10%). The compound is metabolized in the liver and other tissues by transamination (to alpha-ketoglutarate) and deamination (by glutamate dehydrogenase) to form alpha-ketoglutarate, which enters the citric acid cycle. The carbon skeleton is ultimately converted to carbon dioxide (CO2) and water, and the amino group is incorporated into urea or used for the synthesis of other amino acids (e.g., alanine, aspartate). Less than 5% of an oral dose is excreted unchanged in the urine. D-Glutamic acid is not efficiently absorbed from the gastrointestinal tract; the absorbed fraction is largely excreted unchanged in the urine (half-life ~30-60 minutes) without significant metabolism, as mammals lack D-amino acid oxidase for D-glutamate (although D-aspartate oxidase exists). The PK of DL-glutamic acid is dominated by the L-enantiomer after oral administration, with the D-enantiomer being poorly absorbed and largely excreted.
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| Toxicity/Toxicokinetics |
L-Glutamic acid is generally recognized as safe (GRAS) by the FDA when used as a food additive (monosodium glutamate, MSG). The acute oral LD₅0 in rats is >10,000 mg/kg, indicating very low acute toxicity. High oral doses in animals may cause mild gastrointestinal distress (diarrhea, bloating) due to osmotic effects. In humans, ingestion of large amounts of MSG (>3 g in a single meal) may cause a transient sensation of pressure, burning, or tightness in the face, neck, and chest (known as "Chinese Restaurant Syndrome" or the "MSG symptom complex"), but these symptoms are mild and reversible. In rodent models, administration of L-glutamic acid by injection (subcutaneous or IP) to neonatal mice (postnatal days 1-10) has been shown to cause hypothalamic lesions, neuroendocrine disturbances, and obesity (the "MSG-induced obesity" model) at doses of 2-4 g/kg. However, this effect is species-specific and age-dependent; it does not occur in adult animals or in humans at normal dietary intake levels. D-Glutamic acid has low toxicity; the acute oral LD₅0 in rats is >5,000 mg/kg. It is not mutagenic in the Ames test. The compound is not classified as a carcinogen by IARC or NTP. It is not a known reproductive or developmental toxicant. Glutamic acid can be converted to GABA (inhibitory neurotransmitter) and is required for the synthesis of glutathione, an important cellular antioxidant. Excessive activation of glutamate receptors (excitotoxicity) is a mechanism of neuronal injury in conditions such as stroke, traumatic brain injury, amyotrophic lateral sclerosis (ALS), and Alzheimer's disease. However, this is related to the pathophysiological release of endogenous glutamate, not dietary intake. The safety of glutamate in the diet is well established, with the US FDA and EFSA declaring MSG safe for the general population when consumed at customary levels. Standard laboratory safety precautions should be used when handling this compound, including the use of gloves and safety goggles, but no special precautions are required beyond standard laboratory practices.
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| References | |
| Additional Infomation |
DL-Glutamic acid hydrate is the monohydrate crystalline form of a racemic mixture of L- and D-glutamic acid. The L-enantiomer (L-glutamic acid) is one of the 20 proteinogenic amino acids, is a neurotransmitter, and plays a central role in nitrogen metabolism. It is a precursor for the synthesis of GABA (gamma-aminobutyric acid, the main inhibitory neurotransmitter in the brain) via decarboxylation by glutamic acid decarboxylase (GAD). It is also a precursor for the synthesis of glutathione (a tripeptide antioxidant composed of glutamate, cysteine, and glycine) and for the synthesis of proline, arginine, and ornithine. In the food industry, the monosodium salt of L-glutamic acid (monosodium glutamate, MSG) is widely used as a flavor enhancer to impart an umami (savory) taste. The D-enantiomer (D-glutamic acid) is not found in mammalian proteins but is a component of bacterial cell wall peptidoglycan and is present in certain peptides (e.g., poly-gamma-D-glutamate capsule of Bacillus anthracis). The racemic mixture (DL-glutamic acid) is used as a biochemical reagent, a reference standard for HPLC and LC-MS/MS analysis, and a starting material for the synthesis of peptides and other derivatives. It is also used in the production of cosmetics and personal care products. DL-Glutamic acid is not a drug and has not been approved by the FDA, EMA, or other regulatory agencies for the treatment of any human disease. It has not been evaluated in clinical trials as a therapeutic agent (although L-glutamic acid itself and its derivatives are used in various medical contexts, such as in parenteral nutrition, and as the prodrug glutamine in some formulations). This product is intended for laboratory research purposes only, not for human or veterinary diagnostic or therapeutic applications.
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| Molecular Formula |
C5H11NO5
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| Molecular Weight |
165.14
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| Exact Mass |
165.063
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| CAS # |
19285-83-7
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| PubChem CID |
16219385
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| Appearance |
Solid powder
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| Density |
1.4601
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| Boiling Point |
430.7ºC at 760mmHg
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| Melting Point |
194 °C
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| Flash Point |
214.3ºC
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| Vapour Pressure |
8.01E-09mmHg at 25°C
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
11
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| Complexity |
145
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(CC(=O)O)C(C(=O)O)N.O
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| InChi Key |
OZDAOHVKBFBBMZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C5H9NO4.H2O/c6-3(5(9)10)1-2-4(7)8;/h3H,1-2,6H2,(H,7,8)(H,9,10);1H2
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| Chemical Name |
2-aminopentanedioic acid;hydrate
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| Synonyms |
DL-Glutamic acid monohydrate
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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 | 6.0555 mL | 30.2773 mL | 60.5547 mL | |
| 5 mM | 1.2111 mL | 6.0555 mL | 12.1109 mL | |
| 10 mM | 0.6055 mL | 3.0277 mL | 6.0555 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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