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| Targets |
DL-Glutamic acid-d5 does not target biological receptors or enzymes as a labeled internal standard because it is used as an analytical tracer. However, unlabeled Glutamic acid (L-glutamate) is a major excitatory neurotransmitter in the central nervous system that acts on ionotropic (NMDA, AMPA, kainate) and metabotropic (mGluR1-8) glutamate receptors. Glutamate is also a key intermediate in cellular metabolism (e.g., the TCA cycle via alpha-ketoglutarate). Glutamate transporters (EAAT1-5) regulate extracellular glutamate levels. Deuterium labeling does not alter receptor binding properties at tracer concentrations.
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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.[1]
No dedicated in vitro biological activity studies for DL-Glutamic acid-d5 exist, as it is used exclusively as an internal standard. Unlabeled DL-Glutamic acid has identical biological properties to L-glutamic acid (the naturally occurring enantiomer). L-Glutamic acid activates NMDA, AMPA, and kainate receptors (EC50 = 0.5-50 microM depending on receptor subtype). In cell culture, glutamate (0.1-10 mM) induces excitotoxicity in neuronal cells through overactivation of NMDA receptors, leading to calcium influx, oxidative stress, and apoptosis. Glutamate is also an essential energy substrate and nitrogen donor in cellular metabolism. DL-Glutamic acid-d5 at tracer concentrations does not exert these effects. |
| 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.
No in vivo pharmacological studies for DL-Glutamic acid-d5 exist, as it is not administered as a therapeutic agent. Unlabeled L-glutamic acid is involved in learning and memory (long-term potentiation) and is a key molecule in cellular metabolism. Excess glutamate release in the brain contributes to excitotoxicity in stroke, traumatic brain injury, and neurodegenerative diseases (ALS, Huntington's disease). In animal models, L-glutamate (100-500 mg/kg, IV or IP) can induce seizures and excitotoxic neuronal damage. DL-Glutamic acid-d5, when used in tracer studies, would be metabolized identically to unlabeled L-glutamic acid but would not be administered at pharmacologically active doses. |
| Enzyme Assay |
No dedicated cell-free binding protocols for DL-Glutamic acid-d5 exist. For unlabeled L-glutamate in glutamate receptor binding assays: Prepare synaptic membrane preparations from rat brain (cerebral cortex or hippocampus) in 50 mM Tris-HCl, pH 7.4. Incubate membranes (100-200 microg protein) with 10-50 nM [3H]-L-glutamate or [3H]-AMPA (for AMPA receptors) or [3H]-MK-801 (for NMDA receptors) in assay buffer (50 mM Tris-acetate, pH 7.4) for 60 minutes at 4degC. Add unlabeled L-glutamate (1 nM to 100 microM) to compete for binding. Non-specific binding determined in the presence of 1 mM unlabeled L-glutamate or 100 microM NMDA. Terminate by filtration through GF/B filters. Count bound radioactivity by liquid scintillation. For metabotropic receptors, use [3H]-LY341495 as radioligand. For DL-Glutamic acid-d5 as internal standard in binding studies, it can be spiked (10-100 ng/mL) into samples for LC-MS analysis of bound/free glutamate.
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| Cell Assay |
No cell-based assay protocols for DL-Glutamic acid-d5 exist, as it is not used as a test compound. For neuronal excitotoxicity studies with unlabeled L-glutamate: Culture primary cortical neurons or hippocampal neurons (E17-18 rat embryos) in Neurobasal medium with B27 supplement. After 7-14 days in vitro (DIV), treat neurons with L-glutamate (10-500 microM) in the presence of 10 microM glycine (for NMDA receptor activation) for 5-30 minutes at 37degC. Remove glutamate, replace with conditioned medium, and incubate for 24 hours. Assess cell viability by LDH release assay, MTT reduction, or propidium iodide staining. Measure intracellular calcium using Fluo-4 AM. For microglial activation studies, treat BV-2 cells or primary microglia with L-glutamate (100 microM - 5 mM) for 24 hours and measure nitric oxide (Griess assay) and cytokine release (IL-1beta, TNF-alpha, IL-6) by ELISA. For metabolism studies, add L-glutamate (1-10 mM) to cell culture medium and monitor metabolite changes. DL-Glutamic acid-d5 is not used in these protocols as the test compound.
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| Animal Protocol |
No dedicated animal protocols for DL-Glutamic acid-d5 exist. For tracer studies using DL-Glutamic acid-d5: Administer unlabeled glutamic acid (100-500 mg/kg, oral or IV) to rodents along with a fixed amount of DL-Glutamic acid-d5 as internal control. Collect plasma at multiple time points (0, 0.5, 1, 2, 4, 8, 12, 24 hours) in heparinized tubes. For tissue distribution studies, sacrifice animals at predetermined times and harvest brain, liver, kidney, muscle. Homogenize tissues in methanol/water (80:20), add DL-Glutamic acid-d5 as IS, centrifuge, and analyze supernatant by LC-MS/MS. For brain microdialysis studies: Implant microdialysis probe into striatum or hippocampus of anesthetized rats. Perfuse with artificial CSF at 1-2 microL/min. Collect dialysate every 20-30 minutes. Add DL-Glutamic acid-d5 to each fraction as IS for LC-MS/MS quantitation of endogenous or exogenously administered glutamate.
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| ADME/Pharmacokinetics |
No specific PK data for DL-Glutamic acid-d5 exist. PK properties of unlabeled L-glutamic acid: Endogenous plasma levels are 20-100 microM. After oral administration, glutamate undergoes extensive first-pass metabolism in the gut and liver. Oral bioavailability is low (<10%). Peak plasma concentrations occur within 30-60 minutes. Volume of distribution is ~0.2-0.4 L/kg. Plasma half-life is 30-60 minutes in rodents. Clearance occurs primarily through metabolism: glutamate is converted to alpha-ketoglutarate and ammonia by glutamate dehydrogenase, or to glutamine by glutamine synthetase, or used in protein synthesis. Excretion: small amounts excreted unchanged in urine (<5%). Renal reabsorption of glutamate is efficient. Deuterium labeling causes a minor kinetic isotope effect but does not significantly alter PK parameters at tracer doses.
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| Toxicity/Toxicokinetics |
No dedicated toxicity data for DL-Glutamic acid-d5 exist. Unlabeled L-glutamic acid is generally recognized as safe (GRAS) by FDA as a food additive (monosodium glutamate, MSG). Acute toxicity: oral LD50 in rats >5000 mg/kg. Monosodium glutamate has been widely consumed for decades with a favorable safety profile. High doses of MSG (≥5-10 g) may cause mild transient symptoms including headache, sweating, flushing, and chest tightness in sensitive individuals ("Chinese restaurant syndrome"). When injected directly into the brain, glutamate induces excitotoxic neuronal damage. No carcinogenicity, genotoxicity, or teratogenicity concerns for glutamate at physiological levels. Rare allergic reactions reported. DL-Glutamic acid-d5 is for research use only, not for human consumption. The deuterated form has identical toxicity profile.
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| References | |
| Additional Infomation |
Glutamic acid-2,3,3,4,4-d5 is a deuterated compound, in which the hydrogen atoms at positions 2, 3, 3, 4, and 4 of glutamic acid are replaced by deuterium. It is a deuterated compound and also a non-protein α-amino acid.
DL-Glutamic acid-d5 is a research-use only stable isotope-labeled compound, not approved for diagnostic or therapeutic use. It has not been evaluated in clinical trials. Its primary application is as an internal standard for quantitative analysis by NMR, GC-MS, or LC-MS in metabolic analysis, allowing precise tracking and quantification of individual atom movements. Applications include: (1) Quantitation of glutamate in biological samples (plasma, urine, CSF, brain tissue, cell lysates) for metabolomics and biomarker studies; (2) Metabolic flux analysis using stable isotope-resolved metabolomics (SIRM); (3) Studies of glutamatergic neurotransmission and glutamate metabolism; (4) Pharmaceutical drug development where glutamate is an analyte of interest. Glutamic acid is a non-essential amino acid and key neurotransmitter. |
| Molecular Formula |
C5H4D5NO4
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|---|---|
| Molecular Weight |
152.16
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| Exact Mass |
152.084
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| CAS # |
14341-79-8
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| PubChem CID |
56845948
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| Appearance |
Solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
333.8±32.0 °C at 760 mmHg
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| Melting Point |
185ºC (dec)(lit.)
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| Flash Point |
155.7±25.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.522
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| LogP |
-1.43
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
10
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| Complexity |
145
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC(C(C(C(C(=O)O)([2H])N)([2H])[2H])([2H])[2H])=O
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| InChi Key |
WHUUTDBJXJRKMK-UXXIZXEISA-N
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| InChi Code |
InChI=1S/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)/i1D2,2D2,3D
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| Chemical Name |
2-amino-2,3,3,4,4-pentadeuteriopentanedioic acid
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| Synonyms |
DL-Glutamate d5
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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) |
H2O : 25 mg/mL (164.30 mM; with sonication)
DMSO : 1 mg/mL (6.57 mM; with sonication and heat) |
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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 | 6.5720 mL | 32.8601 mL | 65.7203 mL | |
| 5 mM | 1.3144 mL | 6.5720 mL | 13.1441 mL | |
| 10 mM | 0.6572 mL | 3.2860 mL | 6.5720 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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