Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
that is used by almost all living beings in the
biosynthesis
Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...
of
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s. 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
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
in the vertebrate
nervous system
In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
. It serves as the precursor for the synthesis of the inhibitory
gamma-aminobutyric acid (GABA) in GABA-ergic neurons.
Its molecular formula is . Glutamic acid exists in three optically isomeric forms; the dextrorotatory -form is usually obtained by hydrolysis of gluten or from the waste waters of beet-sugar manufacture or by fermentation.
[Webster's Third New International Dictionary of the English Language Unabridged, Third Edition, 1971.] Its molecular structure could be idealized as HOOC−CH()−()
2−COOH, with two
carboxyl
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
groups −COOH and one
amino group
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such a ...
−. However, in the solid state and mildly
acid
In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...
ic water solutions, the molecule assumes an
electrically neutral
Electric charge is the physical property of matter that causes charged matter to experience a force when placed in an electromagnetic field. Electric charge can be ''positive'' or ''negative'' (commonly carried by protons and electrons respe ...
zwitterion
In chemistry, a zwitterion ( ; ), also called an inner salt or dipolar ion, is a molecule that contains an equal number of positively- and negatively-charged functional groups.
: With amino acids, for example, in solution a chemical equilibrium wil ...
structure
−OOC−CH()−()
2−COOH. It is
encoded
In communications and information processing, code is a system of rules to convert information—such as a letter, word, sound, image, or gesture—into another form, sometimes shortened or secret, for communication through a communication ...
by the
codon
The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
s GAA or GAG.
The acid can lose one
proton
A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' elementary charge. Its mass is slightly less than that of a neutron and 1,836 times the mass of an electron (the proton–electron mass ...
from its second
carboxyl group
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
to form the
conjugate base
A conjugate acid, within the Brønsted–Lowry acid–base theory, is a chemical compound formed when an acid donates a proton () to a base—in other words, it is a base with a hydrogen ion added to it, as in the reverse reaction it loses a ...
, the singly-negative
anion
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
glutamate
−OOC−CH()−()
2−COO
−. This form of the compound is prevalent in
neutral
Neutral or neutrality may refer to:
Mathematics and natural science Biology
* Neutral organisms, in ecology, those that obey the unified neutral theory of biodiversity
Chemistry and physics
* Neutralization (chemistry), a chemical reaction in ...
solutions. The
glutamate neurotransmitter plays the principal role in
neural activation.
[Robert Sapolsky (2005), ''Biology and Human Behavior: The Neurological Origins of Individuality'' (2nd edition); ]The Teaching Company
The Teaching Company, doing business as Wondrium, is a media production company that produces educational, video and audio content in the form of courses, documentaries, series under two content brands - Wondrium and The Great Courses. The compa ...
. pp. 19–20 of the Guide Book. This anion creates the savory ''
umami
Umami ( from ja, 旨味 ), or savoriness, is one of the five basic tastes. It has been described as savory and is characteristic of broths and cooked meats.
People taste umami through taste receptors that typically respond to glutamates and ...
'' flavor of foods and is found in
glutamate flavoring
Glutamate flavoring is the generic name for flavor-enhancing compounds based on glutamic acid and its salts (glutamates). These compounds provide an umami (savory) taste to food.
Glutamic acid and glutamates are natural constituents of ma ...
s such as
MSG
Monosodium glutamate (MSG), also known as sodium glutamate, is the sodium salt of glutamic acid. MSG is found naturally in some foods including tomatoes and cheese in this glutamic acid form. MSG is used in cooking as a flavor enhancer wi ...
. In Europe it is classified as food additive
E620. In highly
alkali
In chemistry, an alkali (; from ar, القلوي, al-qaly, lit=ashes of the saltwort) is a basic, ionic salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as a base that dissolves in water. A solution of a ...
ne solutions the doubly negative anion
−OOC−CH()−()
2−COO
− prevails. The
radical
Radical may refer to:
Politics and ideology Politics
*Radical politics, the political intent of fundamental societal change
*Radicalism (historical), the Radical Movement that began in late 18th century Britain and spread to continental Europe and ...
corresponding to glutamate is called glutamyl.
Chemistry
Ionization
![Glutamic Acid at physiological pH V2](https://upload.wikimedia.org/wikipedia/commons/4/4f/Glutamic_Acid_at_physiological_pH_V2.svg)
When glutamic acid is dissolved in water, the
amino group
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such a ...
(−) may gain a
proton
A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' elementary charge. Its mass is slightly less than that of a neutron and 1,836 times the mass of an electron (the proton–electron mass ...
(), and/or the
carboxyl groups may lose protons, depending on the
acidity
In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...
of the medium.
In sufficiently acidic environments, the amino group gains a proton and the molecule becomes a
cation
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
with a single positive charge, HOOC−CH()−()
2−COOH.
[Albert Neuberger (1936), "Dissociation constants and structures of glutamic acid and its esters". ''Biochemical Journal'', volume 30, issue 11, article CCXCIII, pp. 2085–2094. .]
At
pH values between about 2.5 and 4.1,
[ the carboxylic acid closer to the amine generally loses a proton, and the acid becomes the neutral ]zwitterion
In chemistry, a zwitterion ( ; ), also called an inner salt or dipolar ion, is a molecule that contains an equal number of positively- and negatively-charged functional groups.
: With amino acids, for example, in solution a chemical equilibrium wil ...
−OOC−CH()−()2−COOH. This is also the form of the compound in the crystalline solid state. The change in protonation state is gradual; the two forms are in equal concentrations at pH 2.10.[
At even higher pH, the other carboxylic acid group loses its proton and the acid exists almost entirely as the glutamate ]anion
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
−OOC−CH()−()2−COO−, with a single negative charge overall. The change in protonation state occurs at pH 4.07.[ This form with both carboxylates lacking protons is dominant in the ]physiological pH
Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical a ...
range (7.35–7.45).
At even higher pH, the amino group loses the extra proton, and the prevalent species is the doubly-negative anion −OOC−CH()−()2−COO−. The change in protonation state occurs at pH 9.47.[William H. Brown and Lawrence S. Brown (2008), ''Organic Chemistry'' (5th edition). Cengage Learning. p. 1041. .]
Optical isomerism
The carbon
Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent
In chemistry, the valence (US spelling) or valency (British spelling) of an element is the measure of its combining capacity with o ...
atom adjacent to the amino group is chiral
Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object.
An object or a system is ''chiral'' if it is distinguishable from ...
(connected to four distinct groups). Glutamic acid can exist in three optical isomer
In chemistry, a molecule or ion is called chiral () if it cannot be superposed on its mirror image by any combination of rotations, translations, and some conformational changes. This geometric property is called chirality (). The terms are d ...
s, including the dextrorotatory -form, (−), and (+). The form is the one most widely occurring in nature, but the form occurs in some special contexts, such as the bacterial capsule
The bacteria capsule is a large structure common to many bacteria. It is a polysaccharide layer that lies outside the cell envelope, and is thus deemed part of the outer envelope of a bacterial cell. It is a well-organized layer, not easily washe ...
and cell wall
A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mech ...
s of the bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
(which can manufacture it from the form with the enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
glutamate racemase
In enzymology, glutamate racemase (MurI with a capital ''i'') () is an enzyme that catalysis, catalyzes the chemical reaction
:L-glutamate \rightleftharpoons D-glutamate
Hence, this enzyme RacE has one substrate (biochemistry), substrate, glutam ...
) and the liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
of mammals
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
.[National Center for Biotechnology Information,]
D-glutamate
. ''PubChem Compound Database'', CID=23327. Accessed 2017-02-17.
History
Although they occur naturally in many foods, the flavor contributions made by glutamic acid and other amino acids were only scientifically identified early in the 20th century. The substance was discovered and identified in the year 1866 by the German chemist Karl Heinrich Ritthausen
Karl Heinrich Ritthausen (13 January 1826 – 16 October 1912) was a German biochemist who identified two amino acids and made other contributions to the science of plant proteins.
Education
Ritthausen was born in Armenruh, near Goldburg, Sil ...
, who treated wheat gluten
Gluten is a structural protein naturally found in certain cereal grains. Although "gluten" often only refers to wheat proteins, in medical literature it refers to the combination of prolamin and glutelin proteins naturally occurring in all grain ...
(for which it was named) with sulfuric acid
Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid ( Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen and hydrogen, with the molecular formu ...
. In 1908, Japanese researcher Kikunae Ikeda
was a Japanese chemist and Tokyo Imperial University professor of chemistry who, in 1908, uncovered the chemical basis of a taste he named umami. It is one of the five basic tastes along with sweet, bitter, sour and salty.
Ikeda graduated in 1 ...
of the Tokyo Imperial University
, abbreviated as or UTokyo, is a public research university located in Bunkyō, Tokyo, Japan. Established in 1877, the university was the first Imperial University and is currently a Top Type university of the Top Global University Project by ...
identified brown crystals left behind after the evaporation of a large amount of kombu
''Konbu'' (from ja, 昆布, konbu or kombu) is edible kelp mostly from the family Laminariaceae and is widely eaten in East Asia. It may also be referred to as ''dasima'' ( ko, 다시마) or ''haidai'' ().
Kelp features in the diets of many c ...
broth as glutamic acid. These crystals, when tasted, reproduced the ineffable but undeniable flavor he detected in many foods, most especially in seaweed. Professor Ikeda termed this flavor umami
Umami ( from ja, 旨味 ), or savoriness, is one of the five basic tastes. It has been described as savory and is characteristic of broths and cooked meats.
People taste umami through taste receptors that typically respond to glutamates and ...
. He then patented a method of mass-producing a crystalline salt of glutamic acid, monosodium glutamate
Monosodium glutamate (MSG), also known as sodium glutamate, is the sodium salt of glutamic acid. MSG is found naturally in some foods including tomatoes and cheese in this glutamic acid form. MSG is used in cooking as a flavor enhancer wit ...
.
Synthesis
Biosynthesis
Industrial synthesis
Glutamic acid is produced on the largest scale of any amino acid, with an estimated annual production of about 1.5 million tons in 2006. Chemical synthesis was supplanted by the aerobic fermentation of sugars and ammonia in the 1950s, with the organism ''Corynebacterium glutamicum
''Corynebacterium glutamicum'' is a Gram-positive, rod-shaped bacterium that is used industrially for large-scale production of amino acids. While originally identified in a screen for organisms secreting L-glutamate, mutants of ''C. glutamicum' ...
'' (also known as ''Brevibacterium flavum'') being the most widely used for production. Isolation and purification can be achieved by concentration and crystallization
Crystallization is the process by which solid forms, where the atoms or molecules are highly organized into a structure known as a crystal. Some ways by which crystals form are precipitating from a solution, freezing, or more rarely deposi ...
; it is also widely available as its hydrochloride
In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternative na ...
salt.
Function and uses
Metabolism
Glutamate is a key compound in cellular metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
. In humans, dietary proteins
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
are broken down by digestion into amino acids
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
, which serve as metabolic fuel for other functional roles in the body. A key process in amino acid degradation is transamination
Transamination is a chemical reaction that transfers an amino group to a ketoacid to form new amino acids. This pathway is responsible for the deamination of most amino acids. This is one of the major degradation pathways which convert essential a ...
, in which the amino group of an amino acid is transferred to an α-ketoacid, typically catalysed by a transaminase
Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α-keto acid. They are important in the synthesis of amino acids, which form proteins.
Function and mechanism
An amino acid co ...
. The reaction can be generalised as such:
: R1-amino acid + R2-α-ketoacid
In organic chemistry, keto acids or ketoacids (also called oxo acids or oxoacids) are organic compounds that contain a carboxylic acid group () and a ketone group ().Franz Dietrich Klingler, Wolfgang Ebertz "Oxocarboxylic Acids" in Ullmann's En ...
⇌ R1-α-ketoacid + R2-amino acid
A very common α-keto acid is α-ketoglutarate, an intermediate in the citric acid cycle
The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins ...
. Transamination of α-ketoglutarate gives glutamate. The resulting α-ketoacid product is often a useful one as well, which can contribute as fuel or as a substrate for further metabolism processes. Examples are as follows:
: Alanine
Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side c ...
+ α-ketoglutarate ⇌ pyruvate
Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell.
Pyruvic aci ...
+ glutamate
: Aspartate
Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...
+ α-ketoglutarate ⇌ oxaloacetate
Oxaloacetic acid (also known as oxalacetic acid or OAA) is a crystalline organic compound with the chemical formula HO2CC(O)CH2CO2H. Oxaloacetic acid, in the form of its conjugate base oxaloacetate, is a metabolic intermediate in many processes ...
+ glutamate
Both pyruvate and oxaloacetate are key components of cellular metabolism, contributing as substrates or intermediates in fundamental processes such as glycolysis
Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...
, gluconeogenesis
Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrat ...
, and the citric acid cycle
The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins ...
.
Glutamate also plays an important role in the body's disposal of excess or waste nitrogen
Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...
. Glutamate undergoes deamination
Deamination is the removal of an amino group from a molecule. Enzymes that catalyse this reaction are called deaminases.
In the human body, deamination takes place primarily in the liver, however it can also occur in the kidney. In situations of e ...
, an oxidative reaction catalysed by glutamate dehydrogenase
Glutamate dehydrogenase (GLDH, GDH) is an enzyme observed in both prokaryotes and eukaryotic mitochondria. The aforementioned reaction also yields ammonia, which in eukaryotes is canonically processed as a substrate in the urea cycle. Typical ...
, as follows:
: glutamate + H2O + NADP
Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NAD ...
+ → α-ketoglutarate + NADPH
Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NAD ...
+ NH3 + H+
Ammonia (as ammonium
The ammonium cation is a positively-charged polyatomic ion with the chemical formula or . It is formed by the protonation of ammonia (). Ammonium is also a general name for positively charged or protonated substituted amines and quaternary a ...
) is then excreted predominantly as urea
Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid.
Urea serves an important r ...
, synthesised in the liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
. Transamination can thus be linked to deamination, effectively allowing nitrogen from the amine groups of amino acids to be removed, via glutamate as an intermediate, and finally excreted from the body in the form of urea.
Glutamate is also a neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
(see below), which makes it one of the most abundant molecules in the brain. Malignant brain tumors known as glioma
A glioma is a type of tumor that starts in the glial cells of the brain or the spine. Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours.
Signs and symptoms
...
or glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...
exploit this phenomenon by using glutamate as an energy source, especially when these tumors become more dependent on glutamate due to mutations in the gene IDH1
Isocitrate dehydrogenase 1 (NADP+), soluble is an enzyme that in humans is encoded by the ''IDH1'' gene on chromosome 2. Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two ...
.
Neurotransmitter
Glutamate is the most abundant excitatory neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
in the vertebrate nervous system
In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
. At chemical synapses, glutamate is stored in vesicles
Vesicle may refer to:
; In cellular biology or chemistry
* Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane
* Synaptic vesicle
; In human embryology
* Vesicle (embryology), bulge-like features o ...
. Nerve impulses
An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...
trigger the release of glutamate from the presynaptic cell. Glutamate acts on ionotropic and metabotropic
A metabotropic receptor, also referred to by the broader term G-protein-coupled receptor, is a type of membrane receptor that initiates a number of metabolic steps to modulate cell activity. The nervous system utilizes two types of receptors: met ...
(G-protein coupled) receptors. In the opposing postsynaptic cell, glutamate receptors
Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous system an ...
, such as the NMDA receptor
The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA rece ...
or the AMPA receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synapse, synap ...
, bind glutamate and are activated. Because of its role in synaptic plasticity
In neuroscience, synaptic plasticity is the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity. Since memories are postulated to be represented by vastly interconnected neural circuit ...
, glutamate is involved in cognitive functions such as learning
Learning is the process of acquiring new understanding, knowledge, behaviors, skills, value (personal and cultural), values, attitudes, and preferences. The ability to learn is possessed by humans, animals, and some machine learning, machines ...
and memory
Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered, ...
in the brain. The form of plasticity known as long-term potentiation
In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons ...
takes place at glutamatergic synapses in the hippocampus
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
, neocortex
The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, sp ...
, and other parts of the brain. Glutamate works not only as a point-to-point transmitter, but also through spill-over synaptic crosstalk between synapses in which summation of glutamate released from a neighboring synapse creates extrasynaptic signaling/volume transmission
Neuromodulation is the physiology, physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic receptor, metabotropic, G protein-coupled recep ...
. In addition, glutamate plays important roles in the regulation of growth cone
A growth cone is a large actin-supported extension of a developing or regenerating neurite seeking its synaptic target. It is the growth cone that drives axon growth. Their existence was originally proposed by Spanish histologist Santiago Ramó ...
s and synaptogenesis
Synaptogenesis is the formation of synapses between neurons in the nervous system. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development, known as exuberant synaptogenes ...
during brain development as originally described by Mark Mattson
Mark may refer to:
Currency
* Bosnia and Herzegovina convertible mark, the currency of Bosnia and Herzegovina
* East German mark, the currency of the German Democratic Republic
* Estonian mark, the currency of Estonia between 1918 and 1927
* Fi ...
.
Brain nonsynaptic glutamatergic signaling circuits
Extracellular glutamate in ''Drosophila
''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...
'' brains has been found to regulate postsynaptic glutamate receptor clustering, via a process involving receptor desensitization. A gene expressed in glial cell
Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form mye ...
s actively transports glutamate into the extracellular space
Extracellular space refers to the part of a multicellular organism outside the cells, usually taken to be outside the plasma membranes, and occupied by fluid. This is distinguished from intracellular space, which is inside the cells.
The compositi ...
,[ while, in the ]nucleus accumbens
The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for "nucleus adjacent to the septum") is a region in the basal forebrain rostral to the preoptic area of the hypotha ...
-stimulating group II metabotropic glutamate receptors, this gene was found to reduce extracellular glutamate levels. This raises the possibility that this extracellular glutamate plays an "endocrine-like" role as part of a larger homeostatic system.
GABA precursor
Glutamate also serves as the precursor for the synthesis of the inhibitory gamma-aminobutyric acid (GABA) in GABA-ergic neurons. This reaction is catalyzed by glutamate decarboxylase
Glutamate decarboxylase or glutamic acid decarboxylase (GAD) is an enzyme that catalyzes the decarboxylation of glutamate to gamma-aminobutyric acid (GABA) and carbon dioxide (). GAD uses pyridoxal-phosphate (PLP) as a cofactor. The reaction p ...
(GAD), which is most abundant in the cerebellum
The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...
and pancreas
The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...
.
Stiff person syndrome
Stiff-person syndrome (SPS), also known as stiff-man syndrome (SMS), is a rare neurologic disorder of unclear cause characterized by progressive rigidity and stiffness. The stiffness primarily affects the truncal muscles and is superimposed by sp ...
is a neurologic disorder caused by anti-GAD antibodies, leading to a decrease in GABA synthesis and, therefore, impaired motor function such as muscle stiffness and spasm. Since the pancreas has abundant GAD, a direct immunological destruction occurs in the pancreas and the patients will have diabetes mellitus.
Flavor enhancer
Glutamic acid, being a constituent of protein, is present in foods that contain protein, but it can only be tasted when it is present in an unbound form. Significant amounts of free glutamic acid are present in a wide variety of foods, including cheese
Cheese is a dairy product produced in wide ranges of flavors, textures, and forms by coagulation of the milk protein casein. It comprises proteins and fat from milk, usually the milk of cows, buffalo, goats, or sheep. During production, ...
s and soy sauce
Soy sauce (also called simply soy in American English and soya sauce in British English) is a liquid condiment of Chinese origin, traditionally made from a fermented paste of soybeans, roasted grain, brine, and '' Aspergillus oryzae'' or ''Asp ...
, and glutamic acid is responsible for umami
Umami ( from ja, 旨味 ), or savoriness, is one of the five basic tastes. It has been described as savory and is characteristic of broths and cooked meats.
People taste umami through taste receptors that typically respond to glutamates and ...
, one of the five basic taste
The gustatory system or sense of taste is the sensory system that is partially responsible for the perception of taste (flavor). Taste is the perception produced or stimulated when a substance in the mouth reacts chemically with taste receptor ...
s of the human sense of taste
The gustatory system or sense of taste is the sensory system that is partially responsible for the perception of taste (flavor). Taste is the perception produced or stimulated when a substance in the mouth reacts chemically with taste receptor ...
. Glutamic acid often is used as a food additive
Food additives are substances added to food to preserve flavor or enhance taste, appearance, or other sensory qualities. Some additives have been used for centuries as part of an effort to preserve food, for example vinegar (pickling), salt (salt ...
and flavor enhancer
A flavoring (or flavouring), also known as flavor (or flavour) or flavorant, is a food additive used to improve the taste or smell of food. It changes the perceptual impression of food as determined primarily by the chemoreceptors of the gustat ...
in the form of its sodium salt
Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quantitie ...
, known as monosodium glutamate
Monosodium glutamate (MSG), also known as sodium glutamate, is the sodium salt of glutamic acid. MSG is found naturally in some foods including tomatoes and cheese in this glutamic acid form. MSG is used in cooking as a flavor enhancer wit ...
(MSG).
Nutrient
All meats, poultry, fish, eggs, dairy products, and kombu
''Konbu'' (from ja, 昆布, konbu or kombu) is edible kelp mostly from the family Laminariaceae and is widely eaten in East Asia. It may also be referred to as ''dasima'' ( ko, 다시마) or ''haidai'' ().
Kelp features in the diets of many c ...
are excellent sources of glutamic acid. Some protein-rich plant foods also serve as sources. 30% to 35% of gluten (much of the protein in wheat) is glutamic acid. Ninety-five percent of the dietary glutamate is metabolized by intestinal cells in a first pass.
Plant growth
Auxigro
Auxigro is a growth-enhancer that is approved in the United States by the United States Environmental Protection Agency for spray on fruits, vegetables, and grains. It is a mixture of equal parts gamma-aminobutyric acid (GABA), casein hydrolysat ...
is a plant growth preparation that contains 30% glutamic acid.
NMR spectroscopy
In recent years, there has been much research into the use of residual dipolar coupling The residual dipolar coupling between two spins in a molecule occurs if the molecules in solution exhibit a partial alignment leading to an incomplete averaging of spatially anisotropic dipolar couplings.
Partial molecular alignment leads to an inc ...
(RDC) in nuclear magnetic resonance spectroscopy
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fiel ...
(NMR). A glutamic acid derivative, poly-γ-benzyl-L-glutamate (PBLG), is often used as an alignment medium to control the scale of the dipolar interactions observed.
Pharmacology
The drug phencyclidine
Phencyclidine or phenylcyclohexyl piperidine (PCP), also known as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hallucinations, distorted perceptio ...
(more commonly known as PCP or 'Angel Dust') antagonizes glutamic acid non-competitively at the NMDA receptor
The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA rece ...
. For the same reasons, dextromethorphan
Dextromethorphan (DXM) is a medication most often used as a cough suppressant in over-the-counter cold and cough medicines. It is sold in syrup, tablet, spray, and lozenge forms. In 2022, the FDA approved a formulation of it combined with bu ...
and ketamine
Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ne ...
also have strong dissociative
Dissociatives, colloquially dissos, are a subclass of hallucinogens which distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of ...
and hallucinogen
Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorized ...
ic effects. Acute infusion of the drug LY354740 (also known as eglumegad
Eglumetad (INN; also known as eglumegad) is a research drug developed by Eli Lilly and Company, which is being investigated for its potential in the treatment of anxiety and drug addiction. It is a glutamate derived compound and its mode of acti ...
, an agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
of the metabotropic glutamate receptor
The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate rece ...
s 2 and 3) resulted in a marked diminution of yohimbine
Yohimbine (), also known as quebrachine, is an indole alkaloid derived from the bark of the African tree ''Pausinystalia johimbe''; also from the bark of the unrelated South American tree ''Aspidosperma quebracho-blanco''. Yohimbine is an α2- ...
-induced stress response
The fight-or-flight or the fight-flight-or-freeze response (also called hyperarousal or the acute stress response) is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first des ...
in bonnet macaques (Macaca radiata
The bonnet macaque (''Macaca radiata''), also known as zati,Chambers English Dictionary is a species of macaque endemic to southern India. Its distribution is limited by the Indian Ocean on three sides and the Godavari and Tapti Rivers, along wi ...
); chronic oral administration of LY354740 in those animals led to markedly reduced baseline cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
levels (approximately 50 percent) in comparison to untreated control subjects. LY354740 has also been demonstrated to act on the metabotropic glutamate receptor 3
Metabotropic glutamate receptor 3 (mGluR3) is an inhibitory Gi/G0-coupled G-protein coupled receptor (GPCR) generally localized to presynaptic sites of neurons in classical circuits. However, in higher cortical circuits in primates, mGluR3 are lo ...
(GRM3) of human adrenocortical cells, downregulating aldosterone synthase
Aldosterone synthase, also called steroid 18-hydroxylase, corticosterone 18-monooxygenase or P450C18, is a steroid hydroxylase cytochrome P450 enzyme involved in the biosynthesis of the mineralocorticoid aldosterone and other steroids. The enzyme ...
, CYP11B1, and the production of adrenal
The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which ...
steroid
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
s (i.e. aldosterone
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...
and cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
). Glutamate does not easily pass the blood brain barrier
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the Cell (biology), cells, and transports Metabolic waste, metabolic waste products away from th ...
, but, instead, is transported by a high-affinity transport system. It can also be converted into glutamine
Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral, ...
.
See also
References
Further reading
*
External links
Glutamic acid MS Spectrum
{{DEFAULTSORT:Glutamic Acid
Amino acids
Proteinogenic amino acids
Glucogenic amino acids
Acidic amino acids
Dicarboxylic acids
Excitatory amino acids
Flavor enhancers
Umami enhancers
Glutamates
Excitatory amino acid receptor agonists
Glycine receptor agonists
Peripherally selective drugs
Chelating agents
Glutamate (neurotransmitter)
E-number additives