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.

Toxicity Summary
In 1988, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) assessed L-glutamate and its ammonium, calcium, monosodium, and potassium salts. The committee noted that intestinal and hepatic metabolism only leads to elevated systemic glutamate levels after gavage administration of extremely high doses (>30 mg/kg body weight). Ingestion of monosodium glutamate (MSG) is not associated with elevated glutamate levels in breast milk, and glutamate does not readily cross the placental barrier. Infants metabolize glutamate in a similar manner to adults. Routine toxicity studies of MSG administered via the dietary route in various animal populations have not identified any specific toxicities or carcinogenic effects, and reproductive and teratogenicity studies have also found no adverse consequences. Studies have also focused on central nervous system damage following parenteral administration of MSG or gavage administration of extremely high doses in various animals. Comparative studies have shown that newborn mice are most susceptible to neuronal damage; older animals and other species (including primates) are less sensitive. Even with a single addition of 10 grams of monosodium glutamate (MSG) to drinking water, the level of glutamate in human blood is far lower than that observed in newborn mice with hypothalamic injury. Because human studies have failed to confirm a link between MSG and "Chinese restaurant syndrome" or other specific intolerances, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has not set an "Acceptable Daily Intake (ADI)" for glutamate and its salts. The committee considers that glutamate and its salts pose no additional risk to infants. The European Commission's Scientific Committee on Food (SCF) reached similar assessments in 1991. Subsequent reviews by the Federation of American Societies for Experimental Biology (FASEB) and the U.S. Food and Drug Administration (FDA) did not rule out the possibility of sensitive populations, but otherwise aligned with the safety assessments of the JECFA and SCF.

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Interactions
Intraperitoneal injection of monosodium glutamate (MSG) (at a dose of 4 mg/g body weight for 10 days) significantly increased the production of malondialdehyde (MDA) in the liver, kidneys, and brain tissue of rats.
Simultaneous administration of vitamin C, vitamin E, and quercetin to MSG-treated rats significantly reduced MSG-induced increases in MDA. Vitamin E primarily reduced lipid peroxidation in the liver, followed by vitamin C, and lastly quercetin. Vitamin C and quercetin showed stronger protective effects against brain membrane damage than vitamin E. The decrease in glutathione (GSH) in all three organs corresponded to a significant increase in glutathione S-transferase (GST) activity. Glutathione significantly increased (p < 0.001) the activities of superoxide dismutase and catalase in the liver, but significantly decreased the activities of these enzymes in the kidneys and brain. All three antioxidants effectively mitigated the effects of glutathione on GSH levels and enzyme activities in the three organs. Glutathione significantly increased glucose-6-phosphatase activity in the liver and kidneys of rats (p < 0.001), but the activity of this enzyme in the brain was extremely low. Monosodium glutamate (MSG) treatment significantly increased the activities of alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase in rats. The tested antioxidants showed significant protective effects against MSG-induced hepatotoxicity. A dose of 4 mg/g MSG significantly (p < 0.01) induced the formation of micronucleated polychromatic erythrocytes (MNPCEs). The combined treatment of vitamin C and quercetin in rats inhibited monosodium glutamate-induced MNPCEs (p < 0.001)...

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Non-human toxicity values
Oral LD50 of female rats: 15800 mg/kg body weight
Oral LD50 of male rats: 17300 mg/kg/day
Oral LD50 of male mice: 17700 mg/kg body weight
Oral LD50 of female mice: 16400 mg/kg body weight
For more complete non-human toxicity data for monosodium glutamate (24 in total), please visit the HSDB record page.

[1]. Permissive role for mglu1 metabotropic glutamate receptors in excitotoxic retinal degeneration. Neuroscience. 2017 Sep 14. pii: S0306-4522(17)30640-1.

[2]. Presynaptic effect of L-glutamic acid on the release of dopamine in rat striatal slices. Neurosci Lett. 1977 Oct;6(1):73-7.

[3]. L-Glutamic acid monosodium salt reduces the harmful effect of lithium on the development of Xenopus laevis embryos. Environ Sci Pollut Res Int. 2020 Nov;27(33):42124-42132.

[4]. Hydrochloric acid alters the effect of L-glutamic acid on cell viability in human neuroblastoma cell cultures. J Neurosci Methods. 2013 Jul 15;217(1-2):26-30.

[5]. Protective role of l-glutamic acid and l-cysteine in mitigation the chlorpyrifos-induced oxidative stress in rats. Environ Toxicol Pharmacol. 2018 Dec;64:155-163.

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...
Mechanism of Action
L-glutamate and γ-aminobutyric acid (GABA) are considered excitatory and inhibitory neurotransmitters in the central nervous system, respectively. Glutamic acid is also involved in protein synthesis. /Glutamic acid/
Therapeutic Uses
A flavoring agent used to impart a meaty flavor to food. Medically, MSG has been used to lower blood ammonia levels in patients with ammonia nitrogenemia, and to treat hepatic coma, psychosis, and intellectual disability.
Drug Warnings
Treatment of hepatic encephalopathy requires high doses of MSG, which may lead to dangerous alkalosis and hypokalemia...Therefore, close monitoring of electrolyte balance is crucial during treatment.
Monosodium glutamate (MSG) should be administered with caution in patients with cirrhosis, impaired renal function, or liver disease not related to hyperammonemia.
Food and environmental factors: Effects on breastfeeding: Monosodium glutamate: None. /Excerpt from Table 7/

C5H8NNAO4

169.11

169.035

142-47-2

L-Glutamic acid;56-86-0

23672308

White to off-white solid powder

333.8ºC at 760 mmHg

232°C

155.7ºC

2.55E-05mmHg at 25°C

25 ° (C=10, 2mol/L HCl)

2

5

4

11

149

1

C(CC(=O)O)[C@@H](C(=O)[O-])N.[Na+]

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

MSG; Sodium glutamate; Monosodium glutamate

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 : ~7.14 mg/mL (~42.22 mM)
DMSO :< 1 mg/mL

Solubility in Formulation 1: 100 mg/mL (591.33 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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