Everything about Glutamate totally explained
Glutamic acid (abbreviated as
Glu or
E; the abbreviation
Glx or
Z represents either glutamic acid or
glutamine). The
carboxylate anion of glutamic acid is known as
glutamate, and this is one of the 20
proteinogenic amino acids. It isn't among the human
essential amino acids. Its
codons are GAA and GAG.
As its name indicates, glutamic acid has a
carboxylic acid component to its
side chain. At pH7, the
amino group is
protonated and one or both of the
carboxylic groups will be
ionized. Hence, the species has a charge of -1, and is referred to as glutamate. The
pKa value for glutamic acid is 4.1, which means that below this pH, the carboxylic acid groups are not ionized in more than half of the molecules.
History
This compound was discovered in 1908 by the professor Kikunae Ikeda who worked in the Imperial University of Tokyo. He loved seaweed,(Kombu alga, in Japan) which is used like spice in traditional Japanese food. He tried to find the root of this flavour. He discovered that the origin of this taste was the glutamic acid. This man isolated crystals of glutamic acid using a Kombu soup (one hundred grams of Kombu has nearly one gram of glutamic acid ).
Moreover, he discovered that glutamato gave unique flavour to other foods. He called it "umami"(meaning delicious in Japanese). This distinctive flavor has brought glutamate the title of "the elusive fifth taste" to join the more traditional flavors, sweet, salty, sour and bitter.
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Biosynthesis
Function and uses
Metabolism
Glutamate is a key molecule in cellular
metabolism. In humans, dietary
proteins are broken down by digestion into
amino acids, which serves as metabolic fuel for other functional roles in the body. A key process in amino acid degradation is
transamination, in which the amino group of an amino acid is transferred to an α-ketoacid, typically catalysed by a
transaminase. The reaction can be generalised as such:
» R
1-amino acid + R
2-α-ketoacid ⇌ R
1-α-ketoacid + R
2-amino acid
A very common α-ketoacid is α-ketoglutarate, an intermediate in the
citric acid cycle. 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 + α-ketoglutarate ⇌
pyruvate + glutamate
» Aspartate + α-ketoglutarate ⇌
oxaloacetate + glutamate
Both pyruvate and oxaloacetate are key components of cellular metabolism, contributing as substrates or intermediates in fundamental processes such as
glycolysis,
gluconeogenesis and also the
citric acid cycle.
Glutamate also plays an important role in the body's disposal of excess or waste
nitrogen. Glutamate undergoes
deamination, an oxidative reaction catalysed by
glutamate dehydrogenase, as follows:
» glutamate + water +
NADP+ → α-ketoglutarate +
NADPH +
ammonia + H
+
Ammonia (as
ammonium) is then excreted predominantly as
urea, synthesised in the
liver. 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.
Neurotransmitter
Glutamate is the most abundant swift excitatory
neurotransmitter in the mammalian
nervous system. At
chemical synapses, glutamate is stored in vesicles.
Nerve impulses trigger release of glutamate from the pre-synaptic cell. In the opposing post-synaptic cell,
glutamate receptors, such as the
NMDA receptor, bind glutamate and are activated. Because of its role in
synaptic plasticity, it's believed that glutamic acid is involved in cognitive functions like
learning and
memory in the brain.
Glutamate transporters are found in
neuronal and
glial membranes. They rapidly remove glutamate from the
extracellular space. In brain injury or disease, they can work in reverse and excess glutamate can accumulate outside cells. This process causes calcium ions to enter cells via
NMDA receptor channels, leading to neuronal damage and eventual cell death, and is called
excitotoxicity. The mechanisms of
cell death include
Glu/Ca2+-mediated promotion of transcription factors for pro-apoptotic genes, or downregulation of transcription factors for anti-apoptotic genes.
Excitotoxicity due to glutamate occurs as part of the ischemic cascade and is associated with stroke and diseases like amyotrophic lateral sclerosis, lathyrism, autism, some forms of mental retardation and Alzheimer's disease.
Glutamic acid has been implicated in epileptic seizures. Microinjection of glutamic acid into neurons produces spontaneous depolarisations around one second apart, and this firing pattern is similar to what is known as paroxysmal depolarizing shift in epileptic attacks. This change in the resting membrane potential at seizure foci could cause spontaneous opening of voltage-activated calcium channels, leading to glutamic acid release and further depolarization.
Experimental techniques to detect glutamate in intact cells include using a genetically-engineered nanosensor. The sensor is a fusion of a glutamate-binding protein and two fluorescent proteins. When glutamate binds, the fluorescence of the sensor under ultraviolet light changes by resonance between the two fluorophores. Introduction of the nanosensor into cells enables optical detection of the glutamate concentration. Synthetic analogs of glutamic acid that can be activated by ultraviolet light have also been described. This method of rapidly uncaging by photostimulation is useful for mapping the connections between neurons, and understanding synapse function.
Brain nonsynaptic glutamatergic signaling circuits
Extracellular glutamate in Drosophila brains has been found to regulate postsynaptic glutamate receptor clustering, via a process involving receptor desensitization. A gene expressed in glial cells actively transports glutamate into the extracellular space, while in the nucleus accumbens stimulating group II metabotropic glutamate receptors 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
Glutamic acid also serves as the precursor for the synthesis of the inhibitory GABA in GABA-ergic neurons. This reaction is catalyzed by glutamic acid decarboxylase (GAD), which is most abundant in cerebellum and pancreas.
Stiff-man syndrome 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 is also abundant for the enzyme GAD, a direct immunological destruction occurs in the pancreas and the patients will have diabetes mellitus.
Flavor enhancer
soy sauce and is responsible for one of the five basic tastes of the human sense of taste (umami). Glutamic acid is often used as a food additive and flavour enhancer in the form of its sodium salt, monosodium glutamate (MSG).
Nutrient
Overall, glutamic acid is the single largest contributor to intestinal energy. As a source for umami,
Ninety-five percent of the dietary glutamate is metabolized by intestinal cells in a first pass
All meats, poultry, fish, eggs, as well as dairy products are excellent sources of glutamic acid. Some protein-rich plant foods also serve as sources.(External Link)
Plant growth
Auxigro is a plant growth preparation that contains 30% glutamic acid.
Production
China-based Fufeng Group Limited is the largest producer of glutamic acid in the world, with capacity increasing to 300,000 tons at the end of 2006 from 180,000 tons during 2006, putting them at 25 - 30% of the Chinese market. Meihua is the second largest Chinese producer. Together, the top five producers have roughly 50% share in China. Chinese demand is roughly 1.1 million tons per year, while global demand, including China, is 1.7 million tons per year.
Pharmacology
The drug phencyclidine (more commonly known as PCP) antagonizes glutamic acid non-competitively at the NMDA receptor. For the same reasons, sub-anaesthetic doses of Ketamine have strong dissociative and hallucinogenic effects. Glutamate doesn't easily pass the blood brain barrier, but instead this transport is mediated by a high affinity transport system . It can also be converted into glutamine.
Role in Sickle-Cell Disease
A point mutation (valine in place of glutamic acid at position 6) in the β-globin chain of hemoglobin forms HbS. This variant of hemoglobin can cause sickle-cell anemia, where the abnormal hemoglobin are prone to polymerization when deoxygenated, thus distorting the erythrocyte which are removed by the spleen or cause microvascular obstruction (ischemic crises). This trait and disease is common in areas with high prevalence of Plasmodium falciparum (one of three Plasmodium species that causes malaria).
Further Information
Get more info on 'Glutamate'.
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