Excitotoxicity
Encyclopedia
Excitotoxicity is the pathological process by which nerve cells
are damaged and killed by excessive stimulation by neurotransmitter
s such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate
(glutamate receptor
s) such as the NMDA receptor
and AMPA receptor
are overactivated. Excitotoxins like NMDA
and kainic acid
which bind to these receptors, as well as pathologically high levels of glutamate, can cause excitotoxicity by allowing high levels of calcium
ions (Ca2+) to enter the cell
. Ca2+ influx into cells activates a number of enzymes, including phospholipase
s, endonuclease
s, and proteases such as calpain
. These enzymes go on to damage cell structures such as components of the cytoskeleton
, membrane
, and DNA.
Excitotoxicity may be involved in spinal cord injury
, stroke
, traumatic brain injury
, hearing loss (through noise overexposure or ototoxicity
) and in neurodegenerative diseases of the central nervous system
(CNS) such as multiple sclerosis
, Alzheimer's disease
, amyotrophic lateral sclerosis
(ALS), Parkinson's disease
, alcoholism
or alcohol withdrawal and Huntington's disease
. Other common conditions that cause excessive glutamate concentrations around neurons are hypoglycemia
and status epilepticus
.
caused seizure
activity, though this report went unnoticed for several years. The toxicity of glutamate was then observed by D. R. Lucas and J. P. Newhouse in 1957, when the subcutaneous injection of monosodium glutamate
to newborn mice
destroyed the neurons in the inner layers of the retina
. Later, in 1969, John Olney
discovered the phenomenon was not restricted to the retina, but occurred throughout the brain
, and coined the term excitotoxicity. He also assessed that cell death was restricted to postsynaptic neurons, that glutamate agonist
s were as neurotoxic as their efficiency to activate glutamate receptors, and that glutamate antagonist
s could stop the neurotoxicity.
excitotoxins). Glutamate is a prime example of an excitotoxin in the brain, and it is also the major excitatory neurotransmitter in the mammalian CNS. During normal conditions, glutamate concentration
can be increased up to 1mM in the synaptic cleft, which is rapidly decreased in the lapse of milliseconds. When the glutamate concentration around the synaptic cleft cannot be decreased or reaches higher levels, the neuron kills itself by a process called apoptosis
.
This pathologic phenomenon can also occur after brain injury
. Brain trauma
or stroke
can cause ischemia
, in which blood
flow is reduced to inadequate levels. Ischemia is followed by accumulation of glutamate and aspartate in the extracellular fluid
, causing cell death, which is aggravated by lack of oxygen
and glucose
. The biochemical cascade
resulting from ischemia and involving excitotoxicity is called the ischemic cascade
. Because of the events resulting from ischemia and glutamate receptor activation, a deep chemical coma
may be induced in patients with brain injury to reduce the metabolic rate of the brain (its need for oxygen and glucose) and save energy to be used to remove glutamate actively
. (It must be noted that the main aim in induced comas is to reduce the intracranial pressure
, not brain metabolism
).
One of the damaging results of excess calcium in the cytosol is the opening of the mitochondrial permeability transition pore, a pore in the membranes of mitochondria that opens when the organelles absorb too much calcium. Opening of the pore may cause mitochondria to swell and release proteins that can lead to apoptosis
. The pore can also cause mitochondria to release more calcium. In addition, production of adenosine triphosphate
(ATP) may be stopped, and ATP synthase
may in fact begin hydrolysing
ATP instead of producing it.
Inadequate ATP
production resulting from brain trauma can eliminate electrochemical gradient
s of certain ions. Glutamate transporter
s require the maintenance of these ion gradients to remove glutamate from the extracellular space. The loss of ion gradients results not only in the halting of glutamate uptake, but also in the reversal of the transporters, causing them to release glutamate and aspartate into the extracellular
space. This results in a buildup of glutamate and further damaging activation of glutamate receptors.
On the molecular
level, calcium influx is not the only factor responsible for apoptosis induced by excitoxicity. Recently, it has been noted that extrasynaptic NMDA receptor activation, triggered by both glutamate exposure or hypoxic/ischemic conditions, activate a CREB
(cAMP
response element binding) protein
shut-off, which in turn caused loss of mitochondrial membrane potential and apoptosis. On the other hand, activation of synaptic NMDA receptors only activated the CREB pathway
, which activates BDNF (brain-derived neurotrophic factor), not activating apoptosis.
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
are damaged and killed by excessive stimulation by neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate
Glutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
(glutamate receptor
Glutamate receptor
Glutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells. Glutamate is one of the 20 amino acids used to assemble proteins and as a result is abundant in many areas of the body, but it also functions as a neurotransmitter and is particularly abundant in the...
s) such as the NMDA receptor
NMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
and AMPA receptor
AMPA receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system . Its name is derived from its ability to be activated by the artificial glutamate analog AMPA...
are overactivated. Excitotoxins like NMDA
NMDA
N-Methyl-D-aspartic acid or N-Methyl-D-aspartate is an amino acid derivative which acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor...
and kainic acid
Kainic acid
Kainic acid is a natural marine acid present in some seaweed. It is a specific agonist for the kainate receptor used as an ionotropic glutamate receptor which mimics the effect of glutamate...
which bind to these receptors, as well as pathologically high levels of glutamate, can cause excitotoxicity by allowing high levels of calcium
Calcium in biology
Calcium plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization...
ions (Ca2+) to enter the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
. Ca2+ influx into cells activates a number of enzymes, including phospholipase
Phospholipase
A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C and D, distinguished by the type of reaction which they catalyze:*Phospholipase A...
s, endonuclease
Endonuclease
Endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain, in contrast to exonucleases, which cleave phosphodiester bonds at the end of a polynucleotide chain. Typically, a restriction site will be a palindromic sequence four to six nucleotides long. Most...
s, and proteases such as calpain
Calpain
A calpain is a protein belonging to the family of calcium-dependent, non-lysosomal cysteine proteases expressed ubiquitously in mammals and many other organisms. Calpains constitute the C2 family of protease clan CA in the MEROPS database...
. These enzymes go on to damage cell structures such as components of the cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
, membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
, and DNA.
Excitotoxicity may be involved in spinal cord injury
Spinal cord injury
A spinal cord injury refers to any injury to the spinal cord that is caused by trauma instead of disease. Depending on where the spinal cord and nerve roots are damaged, the symptoms can vary widely, from pain to paralysis to incontinence...
, stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
, traumatic brain injury
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...
, hearing loss (through noise overexposure or ototoxicity
Ototoxicity
Ototoxicity is damage to the ear , specifically the cochlea or auditory nerve and sometimes the vestibular system, by a toxin. It is commonly medication-induced; ototoxic drugs include antibiotics such as the aminoglycoside gentamicin, loop diuretics such as furosemide, and platinum-based...
) and in neurodegenerative diseases of the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(CNS) such as multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
, Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...
(ALS), Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
, alcoholism
Alcoholism
Alcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...
or alcohol withdrawal and Huntington's disease
Huntington's disease
Huntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...
. Other common conditions that cause excessive glutamate concentrations around neurons are hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
and status epilepticus
Status epilepticus
Status epilepticus is a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 5 minutes, or recurrent seizures without regaining consciousness between seizures...
.
History
The negative effects of glutamate were first observed in 1954 by T. Hayashi, a Japanese scientist who noted that direct application of glutamate to the CNSCentral nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
caused seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
activity, though this report went unnoticed for several years. The toxicity of glutamate was then observed by D. R. Lucas and J. P. Newhouse in 1957, when the subcutaneous injection of monosodium glutamate
Monosodium glutamate
Monosodium glutamate, also known as sodium glutamate or MSG, is the sodium salt of glutamic acid, one of the most abundant naturally occurring non-essential amino acids....
to newborn mice
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
destroyed the neurons in the inner layers of the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
. Later, in 1969, John Olney
John Olney
John Olney is a medical doctor and neuropathologist known for his work on brain damage. He coined the term excitotoxicity in his 1969 paper published in Science. Olney's lesions are named after him. In 1996 he was elected to the Institute of Medicine of the United States National Academy of Sciences...
discovered the phenomenon was not restricted to the retina, but occurred throughout the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, and coined the term excitotoxicity. He also assessed that cell death was restricted to postsynaptic neurons, that glutamate agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
s were as neurotoxic as their efficiency to activate glutamate receptors, and that glutamate antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
s could stop the neurotoxicity.
Pathophysiology
Excitotoxicity can occur from substances produced within the body (endogenousEndogenous
Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...
excitotoxins). Glutamate is a prime example of an excitotoxin in the brain, and it is also the major excitatory neurotransmitter in the mammalian CNS. During normal conditions, glutamate concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...
can be increased up to 1mM in the synaptic cleft, which is rapidly decreased in the lapse of milliseconds. When the glutamate concentration around the synaptic cleft cannot be decreased or reaches higher levels, the neuron kills itself by a process called apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
.
This pathologic phenomenon can also occur after brain injury
Acquired brain injury
An acquired brain injury is brain damage caused by events after birth, rather than as part of a genetic or congenital disorder such as fetal alcohol syndrome, perinatal illness or perinatal hypoxia. ABI can result in cognitive, physical, emotional, or behavioural impairments that lead to permanent...
. Brain trauma
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...
or stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
can cause ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
, in which blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
flow is reduced to inadequate levels. Ischemia is followed by accumulation of glutamate and aspartate in the extracellular fluid
Extracellular fluid
Extracellular fluid usually denotes all body fluid outside of cells. The remainder is called intracellular fluid.In some animals, including mammals, the extracellular fluid can be divided into two major subcompartments, interstitial fluid and blood plasma...
, causing cell death, which is aggravated by lack of oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
and glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
. The biochemical cascade
Biochemical cascade
A biochemical cascade is a series of chemical reactions in which the products of one reaction are consumed in the next reaction. There are several important biochemical cascade reactions in biochemistry, including the enzymatic cascades, such as the coagulation cascade and the complement system,...
resulting from ischemia and involving excitotoxicity is called the ischemic cascade
Ischemic cascade
The ischemic cascade is a series of biochemical reactions that are initiated in the brain and other aerobic tissues after seconds to minutes of ischemia . This is typically secondary to stroke, injury, or cardiac arrest due to heart attack. Most ischemic neurons that die do so due to the...
. Because of the events resulting from ischemia and glutamate receptor activation, a deep chemical coma
Induced coma
A barbiturate-induced coma, or barb coma, is a temporary coma brought on by a controlled dose of a barbiturate drug, usually pentobarbital or thiopental...
may be induced in patients with brain injury to reduce the metabolic rate of the brain (its need for oxygen and glucose) and save energy to be used to remove glutamate actively
Active transport
Active transport is the movement of a substance against its concentration gradient . In all cells, this is usually concerned with accumulating high concentrations of molecules that the cell needs, such as ions, glucose, and amino acids. If the process uses chemical energy, such as from adenosine...
. (It must be noted that the main aim in induced comas is to reduce the intracranial pressure
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
, not brain metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
).
One of the damaging results of excess calcium in the cytosol is the opening of the mitochondrial permeability transition pore, a pore in the membranes of mitochondria that opens when the organelles absorb too much calcium. Opening of the pore may cause mitochondria to swell and release proteins that can lead to apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. The pore can also cause mitochondria to release more calcium. In addition, production of adenosine triphosphate
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
(ATP) may be stopped, and ATP synthase
ATP synthase
right|thumb|300px|Molecular model of ATP synthase by X-ray diffraction methodATP synthase is an important enzyme that provides energy for the cell to use through the synthesis of adenosine triphosphate . ATP is the most commonly used "energy currency" of cells from most organisms...
may in fact begin hydrolysing
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
ATP instead of producing it.
Inadequate ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
production resulting from brain trauma can eliminate electrochemical gradient
Electrochemical gradient
An electrochemical gradient is a spatial variation of both electrical potential and chemical concentration across a membrane; that is, a combination of the membrane potential and the pH gradient...
s of certain ions. Glutamate transporter
Glutamate transporter
Excitatory amino-acid transporters , formerly known as Glutamate transporters, belong to the family of neurotransmitter transporters. They serve to terminate the excitatory neurotransmitter signal by removal of glutamate from the neuronal synapse into Glia cells.In details, the EAATs are...
s require the maintenance of these ion gradients to remove glutamate from the extracellular space. The loss of ion gradients results not only in the halting of glutamate uptake, but also in the reversal of the transporters, causing them to release glutamate and aspartate into the extracellular
Extracellular
In cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
space. This results in a buildup of glutamate and further damaging activation of glutamate receptors.
On the molecular
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
level, calcium influx is not the only factor responsible for apoptosis induced by excitoxicity. Recently, it has been noted that extrasynaptic NMDA receptor activation, triggered by both glutamate exposure or hypoxic/ischemic conditions, activate a CREB
CREB
CREB is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements , thereby increasing or decreasing the transcription of the downstream genes....
(cAMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
response element binding) protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
shut-off, which in turn caused loss of mitochondrial membrane potential and apoptosis. On the other hand, activation of synaptic NMDA receptors only activated the CREB pathway
Metabolic pathway
In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...
, which activates BDNF (brain-derived neurotrophic factor), not activating apoptosis.
See also
- NeurotoxicityNeurotoxicityNeurotoxicity occurs when the exposure to natural or artificial toxic substances, which are called neurotoxins, alters the normal activity of the nervous system in such a way as to cause damage to nervous tissue. This can eventually disrupt or even kill neurons, key cells that transmit and process...
- Glutamate receptorGlutamate receptorGlutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells. Glutamate is one of the 20 amino acids used to assemble proteins and as a result is abundant in many areas of the body, but it also functions as a neurotransmitter and is particularly abundant in the...
- Glutamatergic system
- Monosodium glutamateMonosodium glutamateMonosodium glutamate, also known as sodium glutamate or MSG, is the sodium salt of glutamic acid, one of the most abundant naturally occurring non-essential amino acids....
- Aspartame controversyAspartame controversyThe artificial sweetener aspartame has been the subject of several controversies since its initial approval by the U.S. Food and Drug Administration in 1974...
- NMDA receptor antagonistNMDA receptor antagonistNMDA receptor antagonists are a class of anesthetics that work to antagonize, or inhibit the action of, the N-methyl d-aspartate receptor . They are used as anesthesia for animals and, less commonly, for humans; the state of anesthesia they induce is referred to as dissociative anesthesia...
- Glutamic acid (flavor)Glutamic acid (flavor)Glutamic acid and its ions and salts, called glutamates, are flavor-enhancing compounds which provide an umami taste to food. Glutamic acid is a natural constituent of many fermented or aged foods, including soy sauce, fermented bean paste, and cheese, and is also a component of hydrolyzed protein...
- Glutamic acidGlutamic acidGlutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
- Soy lecithin
- Nutritional yeastNutritional yeastNutritional yeast is a deactivated yeast, usually Saccharomyces cerevisiae. The scientific work of Louis Pasteur made it possible to isolate yeast in pure culture form. Nutritional yeast is produced by culturing the yeast with a mixture of sugarcane and beet molasses for a period of 7 days and...
- Yeast extractYeast extractYeast extract is the common name for various forms of processed yeast products made by extracting the cell contents ; they are used as food additives or flavourings, or as nutrients for bacterial culture media. They are often used to create savory flavors and umami taste sensations. Monosodium...
Sources
- Kandel EREric R. KandelEric Richard Kandel is an American neuropsychiatrist who was a recipient of the 2000 Nobel Prize in Physiology or Medicine for his research on the physiological basis of memory storage in neurons...
, Schwartz JH, and Jessel TM. 2000. Principles of Neural SciencePrinciples of Neural ScienceFirst published in 1981 by Elsevier, Principles of Neural Science is a neuroscience textbook edited by Eric R. Kandel, James Schwartz, and Thomas Jessell. The original edition was 468 pages; now on the fourth edition, the book has grown to 1414 pages. The second edition was published in 1985, third...
, 4th Edition, Page 928, McGraw Hill - Blaylock RLRussell BlaylockRussell L. Blaylock is a retired neurosurgeon and author. He is a former clinical assistant professor of neurosurgery at the University of Mississippi Medical Center and is currently a visiting professor in the biology department at Belhaven College...
. 1996. Excitotoxins: The Taste That Kills, Health Press, ISBN 0929173252