The AtlasAmino acidsNegatively charged

GlutamateGlu · E

The brain’s main excitatory transmitter, the taste called umami, the fuel the gut burns first, and the hub that most of the body’s nitrogen passes through.

Status Reference · not yet an episodeSources 25Reviewed October 2026

Open in the Atlas Find it on the map

Skeletal formula — every corner and every line end is a carbon, and the hydrogens on carbon are left implied.

Molecule · Glu · 10 heavy atoms

Glutamate

C₅H₉NO₄147.13 g/mol

The brain’s main excitatory transmitter, the taste called umami, the fuel the gut burns first, and the hub that most of the body’s nitrogen passes through.

Built fromthe charted ones open their own entry

C5CarbonH9Hydrogen N Nitrogen O4Oxygen

Codes: Glu · E
Formula: C₅H₉NO₄
Molar mass: 147.13 g/mol
Systematic name: (2S)-2-aminopentanedioic acid
Side chain: 2-Carboxyethyl: two carbons and a carboxylic acid; negatively charged at the pH of blood.
Class: Negatively charged
In the diet: Dispensable
Carbon skeleton: Glucogenic
pKa: α-COOH 2.19 · α-NH₃⁺ 9.67 · side chain 4.25
Isoelectric point: pH 3.22
Hydropathy: -3.5 (Kyte–Doolittle)
Codons: GAA GAG
Main transporters: SLC1A2, SLC1A3 (GLT-1 and GLAST (EAAT2, EAAT1)), SLC17A7 (VGLUT1), SLC1 family (EAATs)

pKa and isoelectric point: Nelson and Cox, Lehninger Principles of Biochemistry, table of amino acid properties (free amino acid, 25 °C). Hydropathy: Kyte and Doolittle, J Mol Biol 1982. Essentiality: Reeds, J Nutr 2000. Formula and mass computed from the structure.

In brief

What it is

An amino acid with a carboxylic acid at the end of its side chain, so it carries a negative charge at the pH of blood. Its sodium salt is monosodium glutamate, MSG ^1,2.

Why it matters

It is the main excitatory neurotransmitter of the brain and the parent of GABA, the main inhibitory one; it is the molecule the umami taste receptor detects; and it is central to amino acid metabolism, to glutathione and to folate ^1,3.

Where it runs short

There is no dietary glutamate deficiency. The body makes it freely, and the gut consumes most of what is eaten: in adults 88% of an enteral glutamate tracer never reached the blood ⁴.

Where it turns

Outside brain cells, too much glutamate kills neurons, which is why astrocytes pump it away; in rats, losing those transporters raised extracellular glutamate and caused neurodegeneration and paralysis ⁵. Eating it does not do this, because the blood–brain barrier actively removes glutamate rather than letting it in ⁶.

A taste, a transmitter or a toxin, depending on which side of which membrane it is on.

The molecule

Glutamate is aspartate with one more carbon in its side chain, which ends in a carboxylic acid. With a pKa near 4.3 it is almost entirely ionised at the pH of blood, so in proteins it carries a negative charge and often binds metal ions or pairs with lysine and arginine.

Some glutamates in proteins are modified after they are made. Adding a second carboxyl group, which needs vitamin K, makes γ-carboxyglutamate, which binds calcium far more tightly; that modification is what makes the clotting factors work ¹.

Charge · pHGlutamate carries a full negative charge at the pH of blood.

Move across the chart to read the charge at any pH.

Computed from its pKa values (α-carboxyl 2.19, α-amino 9.67, side chain 4.25) by the Henderson–Hasselbalch equation, for the free amino acid in water at 25 °C. Inside a folded protein the same groups can shift by a unit or more. The faint lines are the other amino acids.

HydropathyGlutamate scores -3.5: the 3rd most water-loving of the twenty.

Kyte–Doolittle hydropathy index: positive values avoid water and tend to be buried inside a folded protein, negative values sit on its surface. Each letter is an amino acid; choose one to open it.

The genetic codeGlutamate has 2 codons. The code is redundant, so most single-letter changes at the third position still write glutamate.

The 64 codons of the standard genetic code. Codons for glutamate are marked.
1st ↓ 2nd →	U	C	A	G	3rd
U	UUUPhe	UCUSer	UAUTyr	UGUCys	U
	UUCPhe	UCCSer	UACTyr	UGCCys	C
	UUALeu	UCASer	UAAStop	UGAStop	A
	UUGLeu	UCGSer	UAGStop	UGGTrp	G
C	CUULeu	CCUPro	CAUHis	CGUArg	U
	CUCLeu	CCCPro	CACHis	CGCArg	C
	CUALeu	CCAPro	CAAGln	CGAArg	A
	CUGLeu	CCGPro	CAGGln	CGGArg	G
A	AUUIle	ACUThr	AAUAsn	AGUSer	U
	AUCIle	ACCThr	AACAsn	AGCSer	C
	AUAIle	ACAThr	AAALys	AGAArg	A
	AUGMet	ACGThr	AAGLys	AGGArg	G
G	GUUVal	GCUAla	GAUAsp	GGUGly	U
	GUCVal	GCCAla	GACAsp	GGCGly	C
	GUAVal	GCAAla	GAAGlu	GGAGly	A
	GUGVal	GCGAla	GAGGlu	GGGGly	G

Where it comes from

The body makes glutamate from 2-oxoglutarate, either by taking an amino group from another amino acid or by glutamate dehydrogenase, which joins ammonia to it ^1,7. It is one of the most abundant amino acids ¹.

Most of what is eaten is consumed by the gut. In adults given labelled glutamate by nasogastric tube, 88% was taken up on first pass and only 12% reached the blood ⁴; in piglets, 95% of dietary glutamate was metabolised by the gut lining, half of it to CO₂, making glutamate the gut’s largest single fuel ⁸.

DispensableMade in every tissue from 2-oxoglutarate, a Krebs cycle intermediate, by transamination or glutamate dehydrogenase, so there is no dietary requirement ^1,7.

How much

None. The body makes glutamate and the gut burns most of the dietary supply ^4,8.

Where it is in food

Free glutamate gives umami to kelp, the source Ikeda first isolated it from, and to fermented sauces; bound glutamate is in all protein ^1,2.

In the bottle · fermentedMSG was first made in 1909 by breaking down vegetable protein with hydrochloric acid and purifying the glutamate ². Since the late 1950s it has been made by bacterial fermentation of sugar with ammonia, after Japanese researchers found soil bacteria that excrete it ^2,9. The glutamate in MSG is the same L-glutamate as in tomatoes, cheese or kelp.

What the body does with it

In the brain glutamate is the main excitatory neurotransmitter. Neurons load it into vesicles with a dedicated transporter ¹⁰, and it acts on several receptor types, among them the NMDA receptor, whose gating mechanism was resolved structurally in 2024 ¹¹. Astrocytes take it back up through GLAST and GLT-1; without them, glutamate builds up between neurons and kills them ⁵. Glutamic acid decarboxylase turns it into GABA, the main inhibitory transmitter ^1,12.

Elsewhere glutamate is the clearing house of amino acid nitrogen, the first amino acid in glutathione, and the chain of glutamates that holds folate inside cells ^1,13.

On the tongue, T1R1 and T1R3 together form a receptor broadly tuned to L-amino acids, and in humans the combination responds to glutamate, an effect boosted by ribonucleotides ^3,14.

In three sentences each

Umami

The taste receptor T1R1–T1R3 responds to L-glutamate, and ribonucleotides such as those in dried fish and mushrooms strengthen the response, which is the hallmark of umami ^3,14. Kikunae Ikeda isolated glutamate from kelp as the source of the taste in 1908 ².

The main excitatory signal

A vesicular transporter loads glutamate into synaptic vesicles and defines a neuron as glutamatergic; released glutamate opens NMDA and other receptors, and astrocytic transporters clear it again ^5,10,11.

A fence at the brain

In the blood–brain barrier, sodium-driven glutamate transporters sit only on the brain side, pulling glutamate out of brain fluid into the endothelium; the barrier is effectively impermeable to glutamate from blood, even at high concentrations ⁶.

How it is made, moved and broken down

Glutamate dehydrogenase, which turns glutamate into 2-oxoglutarate and ammonia, is regulated: leucine switches it on and GTP switches it off. In the pancreas this is part of how protein stimulates insulin, and in the liver part of how ammonia is fed to the urea cycle ^7,15.

Carbon skeleton · glucogenicConverted back to 2-oxoglutarate, which enters the Krebs cycle; in the gut much of dietary glutamate is burned to CO₂ ^7,8.

Made and unmadeGlutamate and 2-oxoglutarate interconvert ^1,7.

2-Oxoglutarate + amino acid
AminotransferasesGOT, GPT, BCAT · vitamin B6
Glutamate + keto acid
Glutamate dehydrogenaseGLUD1 · NAD(P)⁺; on with leucine, off with GTP
2-Oxoglutarate + NH₄⁺

Into transmitters and glutathioneGlutamate is the parent of GABA and the first unit of glutathione ^12,13.

Glutamate
Glutamic acid decarboxylaseGAD1, GAD2 · vitamin B6
GABA
Glutamate-cysteine ligaseGCLC, GCLM · ATP
γ-Glutamylcysteine → glutathione

How it crosses membranes

SLC1A2, SLC1A3 · GLT-1 and GLAST (EAAT2, EAAT1)astrocytes — clear glutamate from synapses; their loss caused excitotoxic damage in rats ⁵
SLC17A7 · VGLUT1synaptic vesicles of glutamatergic neurons — loads glutamate for release ¹⁰
SLC1 family · EAATsbrain side of the blood–brain barrier — pump glutamate out of the brain ⁶

Where it matters most

Brain: Main excitatory transmitter, and parent of GABA ¹.
Gut: Burns most dietary glutamate on first pass ^4,8.
Pancreatic β-cells and liver: Glutamate dehydrogenase links amino acids to insulin release and to ammonia disposal ⁷.
Tongue: Umami taste through T1R1–T1R3 ³.

When it goes wrong

Inherited

Hyperinsulinism–hyperammonaemia syndrome

GLUD1 · autosomal dominant, often new

Activating mutations make glutamate dehydrogenase resistant to GTP, so protein, especially leucine, provokes excess insulin and hypoglycaemia, with persistently raised ammonia ^7,15. In 48 cases, 52% had mutations in exons 11 and 12, three-quarters of them new ¹⁵.

How it is foundHypoglycaemia with raised ammonia; GLUD1 sequencing ¹⁵.

Acquired

Anti-NMDA receptor encephalitis

GRIN1

Antibodies against the NMDA receptor cause psychiatric symptoms, seizures, abnormal movements and reduced consciousness, mostly in young women; 59% of the first 100 had a tumour, usually an ovarian teratoma ¹⁶. In 577 patients, first-line immunotherapy or tumour removal brought improvement within four weeks in about half ¹⁷.

How it is foundNMDA receptor antibodies in CSF and serum; tumour search ¹⁶.

Acquired

Stiff-person syndrome

GAD2

A rare neurological disorder with high-titre antibodies against glutamic acid decarboxylase and a strong overlap with type 1 diabetes ¹².

How it is foundGAD antibodies ¹².

Drug

Excitotoxicity as a drug target

Memantine, which blocks NMDA receptors, slowed decline in moderate-to-severe Alzheimer’s disease in a 252-patient trial ¹⁸. Neuroprotection in stroke has been harder: in 1,105 patients undergoing clot retrieval, nerinetide, which interferes with NMDA receptor signalling, did not improve outcomes ¹⁹.

How it is measured

Glutamate and glutamine are hard to measure accurately by mass spectrometry because both cyclise to pyroglutamate in the instrument’s ion source; separating the three and using isotope-labelled standards corrects it ²⁰. The clinically important glutamate tests are antibodies: against the NMDA receptor in encephalitis and against glutamic acid decarboxylase in type 1 diabetes and stiff-person syndrome ^12,16.

Plasma glutamate and glutaminePart of the amino acid panel.In electrospray mass spectrometry, free glutamine and glutamate cyclise to pyroglutamate inside the instrument, at least a third and up to nearly all of the glutamine, unless the method separates them and uses isotope standards ²⁰.
Anti-NMDA receptor antibodiesAntibodies against the glutamate NMDA receptor, in cerebrospinal fluid and serum, diagnose anti-NMDA receptor encephalitis ¹⁶.In the first 100 patients, falling serum titres went with improvement ¹⁶.
GAD antibodiesAntibodies against glutamic acid decarboxylase, the enzyme that turns glutamate into GABA ¹².A major autoantibody of type 1 diabetes; found at higher titre in stiff-person syndrome ¹².

Food, supplements and the evidence

Establishedreplicated in people, for a named outcome

Dietary glutamate does not cross the blood–brain barrier ⁶.
MSG eaten with food does not reliably cause headache or other symptoms in blinded studies ^21,22.

Uncertainsmall, short, mixed, surrogate or preclinical

Whether large doses of MSG on an empty stomach cause brief symptoms in people who believe they react. Some unblinded or poorly blinded studies say yes; the best challenge study found the responses inconsistent ^21,23.

Sold asthe claim on the label, against the evidence

“No added MSG” as a health claim. The glutamate in MSG is the same molecule as the glutamate in tomatoes and cheese, most of it is used by the gut, and none of it enters the brain from the blood ^1,4,6.

What is strange about it

The fear of MSG began with a 1968 letter to the New England Journal of Medicine about symptoms after eating at Chinese restaurants ²⁴, and with a 1969 study in which MSG injected under the skin of newborn mice destroyed parts of the hypothalamus ²⁵. Injection into a newborn and eating as an adult are not the same exposure ⁶.

In the largest double-blind challenge, 130 people who said they reacted to MSG were given 5 g without food: 38.5% reacted to MSG alone, 13.1% to placebo alone, and 14.6% to both, and only half of the MSG reactors did so again on retesting ²³.

One of the main autoantigens of type 1 diabetes, found in 1990, turned out to be the enzyme that turns glutamate into GABA ¹².

Where it connects

In the Atlas

GlnGlutaminePolar, uncharged AspAspartateNegatively charged CysCysteinePolar, uncharged GlyGlycineNonpolar, aliphatic LeuLeucineNonpolar, aliphatic

Topics on the map

On the map

A star in Conditional amino acids, one of 14. The brain's main excitatory transmitter and the taste of umami, and the same molecule in both roles — which is why the MSG panic never had a mechanism.

Find it on the map

Sources

25 sources, numbered as they are cited. Every one was checked against PubMed or its publisher before it was cited here; the note under each says what it shows and what it does not.

1
Brosnan JT, Brosnan ME. Glutamate: a truly functional amino acid.Amino Acids · 2013 · 45(3):413–418doi:10.1007/s00726-012-1280-4 · PMID 22526238
Review of glutamate’s roles in metabolism, signalling, taste and haemostasis.
2
Sano C. History of glutamate production.Am J Clin Nutr · 2009 · 90(3):728S–732Sdoi:10.3945/ajcn.2009.27462F · PMID 19640955
Ikeda, kelp, 1908; extraction, then fermentation. Industry author.
3
Li X, Staszewski L, Xu H, et al. Human receptors for sweet and umami taste.Proc Natl Acad Sci U S A · 2002 · 99(7):4692–4696doi:10.1073/pnas.072090199 · PMID 11917125
Human T1R1/T1R3 responds to glutamate, enhanced by ribonucleotides.
4
Matthews DE, Marano MA, Campbell RG. Splanchnic bed utilization of glutamine and glutamic acid in humans.Am J Physiol · 1993 · 264(6 Pt 1):E848–E854doi:10.1152/ajpendo.1993.264.6.E848 · PMID 8101428
14 adults; 88% of enteral glutamate and 54% of glutamine retained on first pass.
5
Rothstein JD, Dykes-Hoberg M, Pardo CA, et al. Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate.Neuron · 1996 · 16(3):675–686doi:10.1016/s0896-6273(00)80086-0 · PMID 8785064
Rats; loss of GLAST or GLT-1 caused excitotoxicity and paralysis.
6
Hawkins RA. The blood-brain barrier and glutamate.Am J Clin Nutr · 2009 · 90(3):867S–874Sdoi:10.3945/ajcn.2009.27462BB · PMID 19571220
The barrier removes glutamate and is impermeable to it from blood.
7
Stanley CA, Lieu YK, Hsu BY, et al. Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene.N Engl J Med · 1998 · 338(19):1352–1357doi:10.1056/NEJM199805073381904 · PMID 9571255
Eight children; GTP-insensitive glutamate dehydrogenase.
8
Reeds PJ, Burrin DG, Stoll B, et al. Intestinal glutamate metabolism.J Nutr · 2000 · 130(4S Suppl):978S–982Sdoi:10.1093/jn/130.4.978S · PMID 10736365
Piglets; 95% of dietary glutamate used by the gut, half oxidised.
9
Kinoshita S, Udaka S, Shimono M. Studies on the amino acid fermentation. Part 1. Production of L-glutamic acid by various microorganisms.J Gen Appl Microbiol · 2004 · 50(6):331–343PMID 15965888
The classic screen for glutamate-producing microbes, republished.
10
Takamori S, Rhee JS, Rosenmund C, et al. Identification of a vesicular glutamate transporter that defines a glutamatergic phenotype in neurons.Nature · 2000 · 407(6801):189–194doi:10.1038/35025070 · PMID 11001057
VGLUT1 loads synaptic vesicles.
11
Chou TH, Epstein M, Fritzemeier RG, et al. Molecular mechanism of ligand gating and opening of NMDA receptor.Nature · 2024 · 632(8023):209–217doi:10.1038/s41586-024-07742-0 · PMID 39085540
Structural basis of NMDA receptor opening.
12
Baekkeskov S, Aanstoot HJ, Christgau S, et al. Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase.Nature · 1990 · 347(6289):151–156doi:10.1038/347151a0 · PMID 1697648
GAD as the 64K autoantigen; high titres in stiff-man syndrome.
13
Lu SC. Glutathione synthesis.Biochim Biophys Acta · 2013 · 1830(5):3143–3153doi:10.1016/j.bbagen.2012.09.008 · PMID 22995213
Glutamate as the first unit of glutathione.
14
Nelson G, Chandrashekar J, Hoon MA, et al. An amino-acid taste receptor.Nature · 2002 · 416(6877):199–202doi:10.1038/nature726 · PMID 11894099
T1R1+T1R3 as a broadly tuned L-amino acid sensor.
15
Stanley CA, Fang J, Kutyna K, et al. Molecular basis and characterization of the hyperinsulinism/hyperammonemia syndrome: predominance of mutations in exons 11 and 12 of the glutamate dehydrogenase gene.Diabetes · 2000 · 49(4):667–673doi:10.2337/diabetes.49.4.667 · PMID 10871207
48 cases; leucine activates the enzyme.
16
Dalmau J, Gleichman AJ, Hughes EG, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies.Lancet Neurol · 2008 · 7(12):1091–1098doi:10.1016/S1474-4422(08)70224-2 · PMID 18851928
100 patients; 59% with tumours.
17
Titulaer MJ, McCracken L, Gabilondo I, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study.Lancet Neurol · 2013 · 12(2):157–165doi:10.1016/S1474-4422(12)70310-1 · PMID 23290630
577 patients; 53% improved within four weeks of first-line treatment.
18
Reisberg B, Doody R, Stöffler A, et al. Memantine in moderate-to-severe Alzheimer’s disease.N Engl J Med · 2003 · 348(14):1333–1341doi:10.1056/NEJMoa013128 · PMID 12672860
252 patients, 28 weeks.
19
Hill MD, Goyal M, Menon BK, et al. Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial.Lancet · 2020 · 395(10227):878–887doi:10.1016/S0140-6736(20)30258-0 · PMID 32087818
1,105 patients; good outcome 61.4% against 59.2%.
20
Purwaha P, Silva LP, Hawke DH, et al. An artifact in LC-MS/MS measurement of glutamine and glutamic acid: in-source cyclization to pyroglutamic acid.Anal Chem · 2014 · 86(12):5633–5637doi:10.1021/ac501451v · PMID 24892977
33% to nearly 100% of glutamine converted in the ion source.
21
Obayashi Y, Nagamura Y. Does monosodium glutamate really cause headache? A systematic review of human studies.J Headache Pain · 2016 · 17:54doi:10.1186/s10194-016-0639-4 · PMID 27189588
No effect with food; studies without food poorly blinded.
22
Geha RS, Beiser A, Ren C, et al. Review of alleged reaction to monosodium glutamate and outcome of a multicenter double-blind placebo-controlled study.J Nutr · 2000 · 130(4S Suppl):1058S–1062Sdoi:10.1093/jn/130.4.1058S · PMID 10736382
Population studies show no untoward effects; responses low and inconsistent.
23
Geha RS, Beiser A, Ren C, et al. Multicenter, double-blind, placebo-controlled, multiple-challenge evaluation of reported reactions to monosodium glutamate.J Allergy Clin Immunol · 2000 · 106(5):973–980doi:10.1067/mai.2000.110794 · PMID 11080723
130 self-reported reactors; inconsistent responses.
24
Kwok RH. Chinese-restaurant syndrome.N Engl J Med · 1968 · 278(14):796doi:10.1056/nejm196804042781419 · PMID 25276867
The letter that named the syndrome.
25
Olney JW. Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate.Science · 1969 · 164(3880):719–721doi:10.1126/science.164.3880.719 · PMID 5778021
Injected into newborn mice.

This is education, not medical advice. Nothing on this page is written with knowledge of your history, your medications or your risks, and nothing here is a dose. Do not start or stop any treatment on the basis of it — talk to your own physician. Read the full medical disclaimer.