Amino acid and neurotransmitter- For the anion in its role as a neurotransmitter, see Glutamate (neurotransmitter).
IUPAC name Glutamic acid
Systematic IUPAC name 2-Aminopentanedioic acid
Other names
- 2-Aminoglutaric acid
CAS Number
- l isomer: 56-86-0
- racemate: 617-65-2
- d isomer: 6893-26-1
3D model (JSmol)
- l isomer: Interactive image
- d isomer: Interactive image
- Zwitterion: Interactive image
- Deprotonated zwitterion: Interactive image
Beilstein Reference
1723801 (L) 1723799 (rac) 1723800 (D)
ChEBI
- l isomer: CHEBI:16015
- racemate: CHEBI:18237
- d isomer: CHEBI:15966
ChEMBL
- l isomer: ChEMBL575060
ChemSpider
- l isomer: 30572
DrugBank
- l isomer: DB00142
- d isomer: DB02517
ECHA InfoCard
100.009.567
EC Number
- l isomer: 200-293-7
E number
E620 (flavour enhancer)
Gmelin Reference
3502 (L) 101971 (rac) 201189 (D)
KEGG
- l isomer: C00025
- d isomer: C00217
PubChem CID
- l isomer: 33032
- d isomer: 23327
UNII
- l isomer: 3KX376GY7L
- racemate: 61LJO5I15S
- d isomer: Q479989WEA
CompTox Dashboard (EPA)
- l isomer: DTXSID0046987
InChI
InChI=1S/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)Key:WHUUTDBJXJRKMK-UHFFFAOYSA-N
- l isomer: InChI=1/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)Key:WHUUTDBJXJRKMK-UHFFFAOYAD
- l isomer: C(CC(=O)O)C@@HN
- d isomer: C(CC(=O)O)C@HN
Zwitterion: C(CC(=O)O)C(C(=O)[O-])[NH3+]
Deprotonated zwitterion: C(CC(=O)[O-])C(C(=O)[O-])[NH3+]
Chemical formula
C5H9NO4
Molar mass
147.130g·mol
Appearance
White crystalline powder
Density
1.4601 (20°C)
Melting point
199°C (390°F; 472K) decomposes
Solubility in water
8.57g/L (25 °C)
Solubility
Ethanol: 350μg/100g (25°C)
Acidity (pKa)
- 2.10 (α-carboxyl; H2O)
- 4.07 (side chain; H2O)
- 9.47 (α-amino; H2O)
Magnetic susceptibility ()
−78.5·10 cm/mol
Hazards
GHS labelling:
Pictograms
Signal word
Warning
Hazard statements
H315, H319, H335
Precautionary statements
P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501
NFPA 704 (firediamond)
2 1 0
Supplementary data page
Glutamic acid (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25°C [77°F], 100kPa).
Infobox references
Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synthesize enough for its use. It is also the most abundant excitatory neurotransmitter in the vertebrate nervous system. It serves as the precursor for the synthesis of the inhibitory gamma-aminobutyric acid (GABA) in GABAergic neurons.
Its molecular formula is C 5H 9NO 4. Glutamic acid exists in two optically isomeric forms; the dextrorotary L-form is usually obtained by hydrolysis of gluten or from the waste waters of beet-sugar manufacture or by fermentation. Its molecular structure could be idealized as HOOC−CH(NH 2)−(CH 2)2−COOH, with two carboxyl groups −COOH and one amino group −NH 2. However, in the solid state and mildly acidic water solutions, the molecule assumes an electrically neutral zwitterion structure OOC−CH(NH 3)−(CH 2)2−COOH. It is encoded by the codons GAA or GAG.
The acid can lose one proton from its second carboxyl group to form the conjugate base, the singly-negative anion glutamate OOC−CH(NH 3)−(CH 2)2−COO. This form of the compound is prevalent in neutral solutions. The glutamate neurotransmitter plays the principal role in neural activation. This anion creates the savory umami flavor of foods and is found in glutamate flavorings such as monosodium glutamate (MSG). In Europe, it is classified as food additive E620. In highly alkaline solutions the doubly negative anion OOC−CH(NH 2)−(CH 2)2−COO prevails. The radical corresponding to glutamate is called glutamyl.
The one-letter symbol E for glutamate was assigned as the letter following D for aspartate, as glutamate is larger by one methylene –CH2– group.
Safety at a Glance
- Toxicity: Excitotoxicity from excessive glutamate is a major mechanism of neuronal death in stroke, traumatic brain injury, and...
- Start with a low dose and wait for onset before redosing
- Test your substance with reagent kits when possible
- Never use alone — have a sober person present
If someone is in crisis, call 911 or Poison Control: 1-800-222-1222
Duration
No duration data available.
How It Feels
Elevated glutamate levels would manifest as a state of heightened neural excitability. Sensory input would feel sharper and more vivid, as though the brain's gain has been turned up. Thoughts would come faster and connect more readily. However, the experience would carry an edge of agitation, as the same excitability that enhances perception can tip into anxiety, restlessness, and difficulty calming the mind. At extreme levels, the overexcitation becomes genuinely painful, manifesting as headache, sensory overload, and the neural equivalent of feedback distortion.
Subjective Effects
The effects listed below are based on the Subjective Effect Index (SEI), an open research literature based on anecdotal reports and personal analyses. They should be viewed with a healthy degree of skepticism. These effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects.
Physical Effects
Cognitive & Perceptual Effects
Cognitive(1)
- Anxiety— Intense feelings of apprehension, worry, and dread that can range from a subtle background unease to...
Multi-sensory(1)
- Sensory overload— An overwhelming flood of sensory information that exceeds the brain's ability to process, creating a...
Pharmacology
Glutamate acts on two categories of receptors: ionotropic (ligand-gated ion channels) and metabotropic (G-protein coupled). The three ionotropic receptor types are named after their selective agonists: NMDA (N-methyl-D-aspartate), AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid), and kainate receptors. NMDA receptors are unique in requiring both glutamate binding and membrane depolarization (to relieve the magnesium block) for activation, making them coincidence detectors critical for Hebbian learning.
AMPA receptors mediate fast excitatory transmission and are the primary drivers of moment-to-moment synaptic communication. Kainate receptors modulate both excitatory and inhibitory transmission. The eight metabotropic glutamate receptors (mGluR1-8) are divided into three groups and modulate synaptic transmission through second messenger cascades.
Glutamate is synthesized from glutamine by glutaminase in presynaptic neurons, and is cleared from the synapse primarily by excitatory amino acid transporters (EAATs) on astrocytes, where it is converted back to glutamine by glutamine synthetase (the glutamate-glutamine cycle).
Interactions
No documented interactions.
History
The role of glutamate as a neurotransmitter was first suggested in 1954 by T. Hayashi, who observed that glutamate application to the brain caused convulsions. However, because glutamate was already known as a common amino acid and metabolic intermediate, the scientific community was skeptical that it could also function as a neurotransmitter. This skepticism delayed acceptance of glutamate's neurotransmitter role for decades.
Jeff Watkins' development of specific glutamate receptor agonists and antagonists in the 1960s-1980s provided the pharmacological tools to study glutamate signaling. The characterization of NMDA, AMPA, and kainate receptor subtypes through the 1980s-1990s, and their subsequent cloning, revealed the molecular basis of excitatory neurotransmission.
The connection between glutamate and learning was solidified when Tim Bliss and Terje Lomo discovered long-term potentiation (LTP) in 1973, and it was later shown that NMDA receptor activation was required for its induction. The excitotoxicity hypothesis, developed by John Olney in the 1960s-1970s, established that glutamate excess could kill neurons, leading to therapeutic strategies for stroke and neurodegeneration using NMDA antagonists like memantine.
Harm Reduction
Glutamate is the primary excitatory neurotransmitter and is not typically consumed directly for psychoactive effects. However, understanding glutamate signaling is relevant for harm reduction because many substances of abuse (alcohol, benzodiazepines, ketamine, PCP) act on glutamate systems.
N-Acetylcysteine (NAC) at 600-1200mg twice daily is the most studied approach for modulating glutamate transmission and shows promise for reducing cravings in substance use disorders. NAC works by activating inhibitory metabotropic glutamate receptors via the cystine-glutamate antiporter system.
Excitotoxicity from glutamate rebound is a concern during withdrawal from GABAergic substances (alcohol, benzodiazepines). This is one mechanism behind withdrawal seizures and why medical supervision for these withdrawals is critical.
Toxicity & Safety
Excitotoxicity from excessive glutamate is a major mechanism of neuronal death in stroke, traumatic brain injury, and neurodegenerative diseases including ALS, Alzheimer's, and Huntington's disease. Excessive NMDA receptor activation causes massive calcium influx, activating proteases, lipases, and endonucleases that destroy the cell. Dietary monosodium glutamate (MSG) does not significantly increase brain glutamate levels in healthy individuals due to blood-brain barrier regulation.
Addiction Potential
Glutamate itself is not addictive, but glutamatergic signaling is involved in the neuroplasticity underlying addiction and drug craving.
Tolerance
| Full | Unknown |
| Half | Unknown |
| Zero | Unknown |
Legal Status
As an endogenous neurotransmitter or hormone naturally produced by the human body, this substance itself is not scheduled or controlled under drug legislation in any major jurisdiction. However, pharmaceutical preparations containing this substance or its synthetic analogues may be regulated as prescription medications depending on the formulation, concentration, and intended use.
In the United States, synthetic or exogenous forms may be regulated by the FDA as drugs if marketed with therapeutic claims. In the European Union, similar regulatory frameworks apply under the European Medicines Agency (EMA). Possession of the endogenous substance in its natural form is not a criminal offense in any jurisdiction.
Tips (5)
Follow evidence-based dosing for Glutamate rather than megadose protocols. More is not always better with supplements, and some have toxicity at high doses. The recommended daily allowance exists for a reason.
Quality varies enormously between Glutamate supplement brands. Look for products with third-party testing (USP, NSF, ConsumerLab). Cheaper brands may contain fillers, incorrect doses, or contaminants.
NAC (N-acetylcysteine) modulates glutamate through the cystine-glutamate antiporter on astrocytes. It increases extracellular glutamate which then activates inhibitory mGlu2/3 autoreceptors on glutamatergic terminals, paradoxically reducing synaptic glutamate release. The net effect is reduced glutamatergic neurotransmission, which is why NAC shows promise for addiction and OCD.
If you are interested in modulating glutamate for therapeutic purposes, NAC at 600-1200mg twice daily is the most studied approach. Effects on glutamate signaling may persist beyond NAC's plasma half-life due to downstream receptor adaptations. Consistent daily dosing appears more important than timing.
Excessive glutamate causes excitotoxicity through massive calcium influx via NMDA receptors, activating destructive enzymes. This is a primary mechanism of neuronal death in stroke and traumatic brain injury. Dietary MSG does not significantly raise brain glutamate levels in healthy individuals because the blood-brain barrier regulates glutamate transport.
Community Discussions (2)
See Also
References (3)
- PubChem: Glutamate
PubChem compound page for Glutamate (CID: 33032)
pubchem - Glutamate - TripSit Factsheet
TripSit factsheet for Glutamate
tripsit - Glutamate - Wikipedia
Wikipedia article on Glutamate
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