Absorption, Distribution and Excretion
Glutamate is absorbed from the intestine via an active transport system specifically designed for amino acids. This process is saturable, competitively inhibited, and dependent on sodium ion concentration… During intestinal absorption, most glutamate undergoes transamination, leading to elevated alanine levels in the portal vein. If large amounts of glutamate are ingested, portal venous glutamate levels also increase… This elevation results in increased hepatic metabolism of glutamate, releasing glucose, lactate, glutamine, and other amino acids into systemic circulation… The pharmacokinetics of glutamate depend on whether it is free or bound to proteins, and the presence of other food components. Digestion of proteins in the intestinal lumen and brush border produces a mixture of small peptides and amino acids; dipeptides and tripeptides may enter absorptive cells and undergo intracellular hydrolysis, releasing more amino acids. Defects are known in the transport of both amino acids and peptides… Glutamate from dietary proteins, as well as endogenous proteins secreted into the intestine, are digested into free amino acids and small peptides, both of which are absorbed by mucosal cells. In mucosal cells, peptides are hydrolyzed into free amino acids, and some glutamate is metabolized. Excess glutamate and other amino acids appear in portal vein blood. Because glutamate is rapidly metabolized in intestinal mucosal cells and the liver, its plasma concentration is low even with high dietary protein intake. Only after gavage administration of extremely high doses (>30 mg/kg body weight) does intestinal and hepatic metabolism lead to elevated systemic glutamate levels. Ingestion of monosodium glutamate (MSG) is not associated with increased glutamate levels in breast milk, and glutamate does not readily cross the placental barrier. Human infants metabolize glutamate in a similar manner to adults. High doses of oral glutamate lead to elevated plasma glutamate levels. Peak plasma glutamate concentration is positively correlated with both dose and concentration… When neonatal rats were gavaged with the same dose (1 g/kg body weight) of an aqueous solution of monosodium glutamate (MSG), increasing the concentration from 2% to 10% resulted in a five-fold increase in the area under the plasma concentration-time curve; similar results were observed in mice… Conversely, when monosodium glutamate (MSG) (1.5 g/kg body weight) was administered to 43-day-old mice via gavage at concentrations ranging from 2% to 20% (w/v), no correlation was found between plasma glutamate levels and the gavage concentration…
Administering a standard dose of 1 g/kg body weight of MSG via gavage in the form of a 10% (w/v) solution resulted in a significant increase in plasma glutamate levels in all studied species. Adult monkeys showed the lowest peak plasma glutamate levels (6 times the fasting level), while mice showed the highest peak plasma glutamate levels (12–35 times the fasting level). Age-related differences were observed between newborn and adult animals; in mice and rats, infants had higher peak plasma concentrations and areas under the curve than adults, while the opposite was observed in guinea pigs.
For more complete data on the absorption, distribution, and excretion of the seven MSGs, please visit the HSDB records page.

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Metabolism/Metabolites
Glutamate is metabolized in tissues via oxidative deamination… or by transamination with pyruvate to oxaloacetate… Oxaloacetate enters the citrate cycle via α-ketoglutarate… Some less frequent but physiologically important pathways in glutamate metabolism include decarboxylation to γ-aminobutyric acid (GABA) and amidation to glutamine… Glutamate decarboxylation to GABA depends on pyridoxal phosphate, which is a coenzyme for glutamate decarboxylase… as is glutamate transaminase. Vitamin B6 deficiency in rats results in elevated serum glutamate levels and delayed glutamate clearance… /Glutamate/
Oral administration of 1 g/kg sodium glutamate to rats resulted in only a slight increase in plasma pyroglutamate levels. Under these conditions, no increase in pyroglutamate or glutamate levels was observed in the brain.

[1]. MEASUREMENT OF DNA DAMAGE, OXIDATIVE STRESS, AND GENE EXPRESSION OF β-CATENIN AND P53 GENES IN LIVER AND BRAIN OF MALE MICE RECEIVING MONOSODIUM L-GLUTAMATE MONOHYDRATE. MEASUREMENT, 2020, 13(7).

Monosodium glutamate (MSG) is a white or off-white crystalline powder with a slightly peptone odor. pH (0.2% solution) 7.0. (NTP, 1992)
A flavoring agent used to impart a meaty flavor to food.
See also: Glutamic acid (with active moiety)...see more...

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Mechanism of Action
L-glutamate and γ-aminobutyric acid (GABA) are considered to be excitatory and inhibitory neurotransmitters in the central nervous system, respectively. Glutamic acid is also involved in protein synthesis. /Glutamic acid/

C5H10NNAO5

187.13

187.045

6106-04-3

L-Glutamic acid-13C5 hydrate salt;202114-62-3

23672308

White free flowing crystals or crystalline powder
Forms rhombic prisms when crystallized from water

333.8ºC at 760 mmHg

232 °C (dec.)(lit.)

155.7ºC

2

5

4

11

149

1

O([H])C([C@]([H])(C([H])([H])C([H])([H])C(=O)O[H])N([H])[H])=O

LPUQAYUQRXPFSQ-DFWYDOINSA-M

InChI=1S/C5H9NO4.Na/c6-3(5(9)10)1-2-4(7)8;/h3H,1-2,6H2,(H,7,8)(H,9,10);/q;+1/p-1/t3-;/m0./s1

sodium;(2S)-2-amino-5-hydroxy-5-oxopentanoate

2934.99.9001

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.

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

H2O: 100 mg/mL (534.39 mM)

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.)