L-glutamate can affect the release of [3H]DA by absorbing glutamate at the presynaptic level. Even with 0.5 μM of tetrodotoxin present, 50 μM of L-glutamic acid can still induce the release of [3H]DA [1].

Absorption, Distribution and Excretion
Absorbed from the small intestinal lumen into intestinal cells. Absorption is highly efficient, occurring via an active transport mechanism. /Breast Milk/ Previous short-term observational studies of free amino acid (FAA) content in human milk showed that glutamine and glutamate increased within 4 to 6 weeks postpartum. This study measured changes in free amino acid (FAA) content in colostrum, at 1 month, and 3 months of lactation in 16 healthy lactating women after full-term delivery. Milk was collected within 24 hours at the end of each feeding (hindmilk). Glutamate and taurine were the most abundant free amino acids in colostrum. Although taurine remained stable throughout lactation, the levels of glutamate (the major free amino acid) and glutamine increased by approximately 2.5-fold and 20-fold, respectively, accounting for more than 50% of total free amino acids at 3 months of lactation. The content of essential free amino acids also remained stable, so the change in total free amino acid content was almost entirely attributed to changes in glutamate and glutamine. The intake of glutamine and glutamate gradually increased in breastfed infants throughout the lactation period. Increased intake of glutamate and glutamine may benefit breastfed infants, as the molecules they provide may have protective effects on the intestinal mucosa, act as neurotransmitters, and serve as a nitrogen source. In this report, we synthesized L-glutamine and L-glutamate labeled with 13N using an enzymatic method… Organ distribution studies and whole-body scans in mongrel dogs showed that myocardial uptake of glutamine and glutamate was low, while hepatic uptake of glutamine was higher than that of glutamate or ammonia. The intestinal metabolism of the nitrogen fraction of glutamate was investigated by oral administration of L-[(15)N]glutamate and collection of arterial blood samples. Six healthy adults with an average weight of 72.8 kg ingested 100 mg of L-[(15)N]glutamate after overnight fasting, and measurements were taken. The isotopic enrichment of glutamate, glutamine, and alanine in arterial blood was determined by gas chromatography-mass spectrometry. The isotopic enrichment of amino acids was continuously monitored within 150 minutes after amino acid ingestion. The concentration of amino acids in arterial and venous blood was determined by high-performance liquid chromatography (HPLC), and the results showed no significant changes during the experiment. From the observed labeling in arterialized glutamate, alanine, and glutamine, only a small amount of luminal glutamate reached the extracellular pool. Most of the exogenous nitrogen labeling appeared in the arterial alanine and glutamine components.

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Metabolism/Metabolites
Liver
Cortical excitability reflects the balance between excitation and inhibition. Glutamate is the main excitatory neurotransmitter in the mammalian cortex, while GABA is the main inhibitory neurotransmitter. Changes in glutamate and GABA metabolism may play an important role in the control of cortical excitability. Glutamate is a metabolic precursor of GABA and can be recycled through the tricarboxylic acid cycle to synthesize glutamate. GABA synthesis is unique among neurotransmitters, with its rate-limiting enzyme—glutamate decarboxylase—having two distinct isoenzymes. GABA synthesis requires two independent genes on two chromosomes for control, the reason for which remains unclear. The concentrations of two GABA metabolites are abnormally high in the human brain. High carnosine and pyrrolidone significantly affect GABA metabolism in the human brain. Both GABA metabolites possess anticonvulsant properties and can significantly influence cortical excitability. /Glutamate, GABA/
This study investigated the intestinal metabolism of the nitrogen fraction of glutamate by oral administration of L-[(15)N]glutamate and collection of arterial blood samples. The study included six healthy adults with an average weight of 72.8 kg who received 100 mg of L-[(15)N]glutamate orally after overnight fasting. Gas chromatography-mass spectrometry was used to determine the enrichment of glutamate, glutamine, and alanine in arterial blood. Aminotopic enrichment of amino acids was monitored for 150 minutes after ingestion. High-performance liquid chromatography (HPLC) was used to determine the amino acid concentration in arterialized venous blood. Results showed no significant changes during the experiment. The observed markers in arterialized glutamate, alanine, and glutamine indicated that only a small amount of glutamate from the lumen entered the extracellular pool. Most of the nitrogen-intake markers appeared in the alanine and glutamine components of the arterial blood.
Liver

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

L-Glutamic acid is an optically active glutamate with an L-configuration. It is a nutritional supplement, micronutrient, E. coli metabolite, mouse metabolite, ferroptosis inducer, and neurotransmitter. It belongs to the glutamine family of amino acids, protein synthesis amino acids, glutamate, and L-α-amino acids. It is the conjugate acid of L-glutamate (1-). It is the enantiomer of D-glutamate. It is a peptide composed of glutamate homopolymers. L-Glutamic acid is a metabolite found in or produced by E. coli (K12 strain, MG1655 strain). Glutamic acid has also been reported in Streptomyces churnii, Pinus tabuliformis, and other organisms with relevant data. Glutamic acid is a non-essential α-amino acid and an excitatory neurotransmitter. Glutamic acid can serve as a precursor for the synthesis of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Glutamate (Glu), also known as glutamate (anion), is one of the 20 amino acids required for protein synthesis, but it is not an essential amino acid. Glutamate is a key molecule in cellular metabolism. In the human body, dietary protein is digested and broken down into amino acids, which are used as metabolic fuel or for other physiological functions. Glutamate is the most abundant rapidly excitatory neurotransmitter in the mammalian nervous system. At chemical synapses, glutamate is stored in vesicles. Nerve impulses trigger the release of glutamate from presynaptic cells. In contralateral postsynaptic cells, glutamate receptors (such as NMDA receptors) bind to and are activated by glutamate. Due to its role in synaptic plasticity, glutamate is believed to be involved in cognitive functions of the brain, such as learning and memory. Glutamate transporters are present on the membranes of neurons and glial cells, and they can rapidly remove glutamate from the extracellular space. In brain injury or disease states, the function of these transporters can be reversed, leading to an excessive accumulation of glutamate outside the cell. This process promotes the entry of calcium ions into the cell through NMDA receptor channels, causing neuronal damage and ultimately cell death; this process is known as excitotoxicity. Mechanisms of cell death include: Excessive intracellular Ca2+ concentration leading to mitochondrial damage; Glutamate/Ca2+-mediated activation of pro-apoptotic gene transcription factors, or downregulation of anti-apoptotic gene transcription factors. Glutamate-induced excitotoxicity is part of the ischemic cascade and is associated with stroke, amyotrophic lateral sclerosis (ALS), pea poisoning, and Alzheimer's disease. Glutamate is also associated with epileptic seizures. Microinjection of glutamate into neurons produces spontaneous depolarization at approximately one-second intervals, a firing pattern similar to the paroxysmal depolarization shifts in epileptic seizures. This change in the resting membrane potential of the epileptic focus may lead to the spontaneous opening of voltage-gated calcium channels, resulting in glutamate release and further depolarization. Glutamate is a non-essential amino acid, naturally occurring among L-amino acids. It is the most common excitatory neurotransmitter in the central nervous system. See also: Monosodium glutamate (active ingredient); glutamate hydrochloride (salt form); glatiramer acetate (monomer)... See more...

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Drug Indications
Considered a natural "brain food" that can improve cognitive abilities; helps accelerate ulcer healing; relieves fatigue; and helps control alcohol addiction, schizophrenia, and sugar cravings.

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Mechanism of Action
Glutamate activates ionotropic and metabolotropic glutamate receptors. Ionotropic receptors include non-NMDA receptors (AMPA and fumarate receptors) and NMDA receptors. Free glutamate cannot cross the blood-brain barrier in large quantities; it is converted into L-glutamine, which the brain uses for energy and protein synthesis. Glutamate is presumably involved in cognitive functions of the brain, such as learning and memory, but excessive glutamate can lead to neuronal damage and is associated with diseases such as amyotrophic lateral sclerosis, pea poisoning, and Alzheimer's disease. In addition, the drug phencyclidine (more commonly known as PCP) can antagonize glutamate on NMDA receptors, leading to schizophrenia-like behavior. Because the effects of glutamate are transient, it is difficult to study its effects.

C5H9NO4

147.1293

147.053

56-86-0

L-Glutamic acid monosodium salt;142-47-2;L-Glutamic acid-1-13C;81201-99-2;L-Glutamic acid-15N;21160-87-2;L-Glutamic acid-13C5,15N;202468-31-3;L-Glutamic acid-13C5;55443-55-5;L-Glutamic acid-d5;2784-50-1;L-Glutamic acid-d3;203805-84-9;L-Glutamic acid-13C;115473-51-3;L-Glutamic acid-13C2;115473-56-8;L-Glutamic acid-13C5,15N,d5;1420815-74-2;L-Glutamic acid-5-13C;81202-00-8;L-Glutamic acid-15N,d5

33032

White to off-white solid powder

1.4±0.1 g/cm3

333.8±32.0 °C at 760 mmHg

205 °C (dec.)(lit.)

155.7±25.1 °C

0.0±1.5 mmHg at 25°C

1.522

-1.43

3

5

4

10

145

1

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

WHUUTDBJXJRKMK-VKHMYHEASA-N

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

(2S)-2-aminopentanedioic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

H2O : ~6.25 mg/mL (~42.48 mM)
DMSO :< 1 mg/mL

Solubility in Formulation 1: 9.09 mg/mL (61.78 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

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