Glutamine and GABA

"The action of the heart is under considerable control of the nervous system, and the pathways involved in the neural control of cardiovascular function happen to rely on glutamate and GABA. If the brain has a faulty glutamine / glutamate / GABA metabolism, we can expect the development of cardiovascular dysfunction as well. In addition, glutamine serves as a substrate for the synthesis of a special type of beta-endorphin, glycyl-l-glutamine. This dipeptide appears to be important for the regulation of blood pressure and prevention of cardiorespiratory depression. Glycyl-l-glutamine is also important for the immune response, since it enhances the activity of the natural killer (NK) cells."(1.)

"The synthesis of glutamine protects the body, and the brain in particular, from ammonia toxicity. In fact, the synthesis of glutamine from glutamate is the key pathway for detoxifying ammonia. Excess ammonia is a crucial factor in the development of neurodegenerative diseases, since ammonia interferes with the oxidative metabolism of neurons and thus reduces the production of ATP, our "energy molecule." In addition, ammonia gives rise to very harmful nitrogen-based free radicals."(1.)

"In the brain, glutamine is a substrate for the production of both excitatory and inhibitory neurotransmitters (glutamate and gamma-aminobutyric acid, popularly known as GABA). Glutamine is also an important source of energy for the nervous system. If the brain is not receiving enough glucose, it compensates by increasing glutamine metabolism for energy-hence the popular perception of glutamine as "brain food" and its use as a pick-me-up. Glutamine users often report more energy, less fatigue and better mood."(1.)

"Glutamine also plays a part in maintaining proper blood glucose levels and the right pH range. The body has an exquisite mechanism for maintaining pH homeostasis. If the pH of the blood is too acidic, more glutamine is directed to the kidneys, where a certain type of glutamine results in the release of bicarbonate ions to correct acidosis. If the pH is too alkaline, more glutamine is sent to the liver, where a different kind of metabolism releases hydrogen ions to correct alkalosis."(1.)

"And there is still more. Due to its dependence on sodium transport, glutamine is one of the amino acids that control the volume of water in the cells, and the osmotic pressure (osmoregulation) in various tissues. Glutamine also plays a vital part in the control of blood sugar. It helps prevent hypoglycemia , since it is easily converted to glucose when blood sugar is low. In addition, glutamine regulates the expression of certain genes, including those that govern certain protective enzymes, and helps regulate the biosynthesis of DNA and RNA. Recently it has been discovered that glutamine is important for the cardiovascular system as well."(1.)

"The glutamine cycle in the brain is simple and elegant. Glutamine readily crosses the blood-brain barrier. Neurons take up glutamine and convert it to glutamate or GABA (through the additional step of decarboxylating the glutamate). Some glutamate is used for energy, some for synthesis of glutathione and niacin, some as neurotransmitter. After either glutamate or GABA are released into the synaptic junction, the supportive cells called glia, with their high supply of glutamine synthase, take up the glutamate or GABA and resynthesize glutamine, detoxifying ammonia in the process. The glutamate that is not converted to glutamine is used by the glia as a source of energy, and also to produce energy nutrients alanine and alpha-ketoglutarate, which are then released to the neurons."(1.)

"If excess glutamine accumulates through the action of the glia, the brain donates it to the body. Normally, however, very little glutamine is released by the brain, in contrast to muscle and adipose tissue, which donate a lot. In the brain, it's pretty much an internal affair. What we see is the glutamine glutamate GABA glutamine cycle."(1.)

"If the glia are dysfunctional due to reduced aerobic metabolism, or the release and/or activity of the glial glutamine synthase is inhibited in any way (free-radical damage, toxins, certain drugs), not only glutamate, but GABA as well might accumulate in excess, possibly causing lethargy and cognitive dysfunction. It has been suggested that this too is one of the phenomena we see in the aging brain. On the one hand, glutamate excitotoxicity damages or destroys some neurons, leading to deficiencies in memory and learning; on the other hand, excess of GABA can lead to lethargy. At the same time, excess ammonia, not detoxified through sufficient glutamine synthesis by the glia, leads to further neural damage."(1.)

"An interesting development related to glutamate is the increasing use of ampakines, a new class of drugs for Alzheimer's disease. Apparently an important factor in the pathogenesis of Alzheimer's disease is stroke or a series of undiagnosed mini-strokes. During stroke, the dying neurons release glutamate, which then unfortunately can cause more neuron death. Furthermore, ischemic episodes damage the glutamate receptors, so that later the glutamate can't work as a neurotransmitter. Without glutamate, there is no memory and no learning. Ampakines amplify the glutamate signal through a yet unknown mechanism, possibly by rebuilding glutamate receptors. In healthy people and in animals, ampakines have been shown to enhance cognitive performance, and can thus be classified as "smart drugs."(1.)

Glutamate

"One current hypothesis is that glutamate is also deficient in schizophrenia, though probably many neurotransmitters are out of balance in neurological disorders."(1.)

"At normal physiological levels, glutamate is beneficial and safe. It is an indispensable neurotransmitter that the brain produces according to need. When the central nervous system is aroused, surprisingly enough we do not see higher glucose consumption. Instead, some of the glucose is converted to glutamate. The other source of glutamate is, of course, glutamine. An abundant supply of glutamine makes it easier for the brain to maintain neurotransmitter balance, by increasing the production of glutamate when required for alertness, learning and memory, and the production of GABA when its inhibitory properties are needed. In fact, some people report feeling more centered and calm after they start taking glutamine. Others report a lifting of depression."(1.)

"Glutamate is our chief excitatory neurotransmitter. It is essential for learning and both short-term and long-term memory. Problems arise only if the normal process of glutamate removal and conversion to glutamine malfunctions and an excess of this excitatory neurotransmitter builds up in the synaptic junctions. Excess glutamate causes excessive influx of calcium ions into the neurons, causing excitotoxicity and ultimately even death of the neurons. It also destroys glutathione, a crucial brain-protective antioxidant. Low levels of brain glutathione are associated with neurodegenerative disorders. Glutathione depletion further leads to neuronal death."(1.)

"Under what conditions do we see excess levels of glutamate at the synapses? Not surprisingly, we see evidence of damage associated with excess glutamate in Alzheimer's disease patients, AIDS patients (the AIDS virus inhibits glutamate uptake by the glia), cancer patients (according to one hypothesis, cancer basically starts with brain dysfunction), and in those who have suffered a severe brain injury. Very high fever or artificially induced hyperthermia can also result in excess glutamate release, leading to seizures."(1.)

"GLUTAMINE--As well as cysteine it is recommended to take the other two aminos that make up glutathione as supplemental glycine and glutamine. Both glutamate and glutamine are forms of glutamic acid, the body easily converts the glutamine to glutamic acid. Glutamic acid readily passes the blood brain barrier and is considered a "brain fuel."(2.)

"In the brain, glutamine is a substrate for the production of both excitatory and inhibitory neurotransmitters (glutamate and GABA). Glutamine is also an important source of energy for the nervous system. Glutamic acid and cysteine are necessary for glucose regulation, and can decrease cravings for alcohol and sugar. If the brain is not receiving enough glucose, it compensates by increasing glutamine metabolism for energy. Glutamine users often report more energy, less fatigue and better mood.(sic.)"(2.)

"Glutamine is the most abundant single amino acid in the blood and in the muscle tissue comprising up to 60% of the amino acid pool in skeletal muscle; and is manufactured and released primarily by the skeletal muscle. Because it is important in the rapid growth of cells more is needed during stress or illness. Glutamine is utilized as a source of energy and for nucleotide synthesis by all rapidly dividing cells, such as the cells of the intestinal lining and certain immune cells thus without sufficient glutamine, the intestines atrophy and the immune function breaks down. Glutamine therapy was found to improve intestinal permeability in AIDS patients."(2.)

"Glutamine serves as a nitrogen donor and a carbon donor, and is thus an important muscle-building amino acid. Glutamine's unique structure, containing two nitrogen side chains makes it responsible for 35% of the nitrogen that gets into the muscle cell. It is anticatabolic, meaning it regulates protein synthesis in muscles, sparing muscle tissue and helps replenish muscle glycogen after exercise. It is also involved in glycogen synthesis in the liver and is a building block of many other amino acids. Glutamine can increase growth hormone levels by 43% thereby slowing aging. It also improves lymphocyte proliferation. Further more it reduces insulin resistance and high blood sugar which also counteracts aging."(2.)

"The amino acid glutamine strengthens the cell lining of both the small and large intestines, provides metabolic fuel for gut cells, brain cells, immune macrophages and lymphocytes. Glutamine has been reported to be helpful in reducing "leaky gut" and "brain fog". Glutamine is important as an energy source for our bodies, and is the primary fuel for the upper intestinal tract. It aids the immune system by increasing the integrity of the intestinal lining preventing toxins and pathogens from entering the bloodstream. Glutamine is also a component of folic acid. There is an association between folic acid deficiency and seizure. Disruptions of the intestinal lining may cause folate deficiency, and consequently lead to seizures."(2.)

"The small intestine uses 40% of the glutamine in the body, it being the primary amino acid for the cells that line the small intestine; it nourishes and repairs them. Insufficient glutamine increases the permeability of the gut leading to leaky gut syndrome. This lets in toxins, pathogens and partially digested molecules into the blood increasing the load on the liver. The large molecules entering the bloodstream stimulate antibody production, and then the liver subsequently has to cope with the waste products of antibodies. Which again increases the demands made on glutathione and other antioxidants."(2.)

"GABA--GABA is made from the amino acid Glutamic acid (Glutamine or Glucose). It reduces anxiety, elevates the pain threshold reduces the blood pressure and heart rate and reduces compulsive behavior. GABA promotes fat loss and stimulates the production of Human Growth Hormone (HGH). GABA can be taken as a supplement (L-Glutamine), produces a calming effect on people who struggle with temporal lobe symptoms like temper, irritability, and anxiety."(2.)

"GLYCINE--Glycine and glucose are the two most common amino acids in the body. Glycine is the simplest amino acid and is the only protein forming amino acid without a center of chirality, that is it is nonpolar. Because glycine has such a small side chain it can fit into many places where no other amino acid can. Hence it is the internal amino acid of a collagen helix, thus collagen is about one-third glycine. Most proteins however only contain a small quantity of glycine."(2.)

"Like GABA, Glycine activates Cl- ion conductance resulting in a hyperpolarization of the neuronal membrane and an antagonism of other depolarizing stimuli. This membrane hyperpolarization makes glycine the major inhibitory neurotransmitter in the brainstem and spinal cord, where it participates in a variety of motor and sensory functions. However in the forebrain it functions in an excitatory way by promoting the actions of the major excitatory neurotransmitter glutamate at the NMDA receptors. Other amino acids, including alanine and taurine, also activate glycine receptors, but with lower potency."(2.)

"Glycine may increase acetylcholine neurotransmission in the hippocampus, the memory center of the brain. This factor could be involved in having "ones life pass before ones eyes" during near death experiences. Increases blood sugar and Growth Hormone. Vitamin B6, magnesium and dimethylglycine are antiseizure and have increased speech in autistic children. Found in many foods, glycine is also synthesized in the human body where, among other functions it helps improve glycogen storage. It is utilized in the synthesis of hemoglobin, collagen and glutathione, and facilitates the amelioration of high blood fat and uric acid levels."(2.)

"It is essential for learning and both short-term and long-term memory. Glutamate, as a neurotransmitter, exists in the extracellular fluid only in very, very small concentrations--no more than 8 to 12 FM (micromoles/liter). When the concentration of this transmitter rises above this level, the neurons begin to fire abnormally. At higher concentrations, the cells undergo a specialized process of delayed cell death known as excitotoxicity; that is, they are excited to death. Some individuals may be especially sensitive and develop severe symptoms and even die suddenly from cardiac irritability, but in most instances the effects are subtle and develop over a long period of time. But, it is free glutamate that is the culprit. Bound glutamate, found naturally in foods, is less dangerous because it is slowly broken down and absorbed by the gut so that the tissues can utilize it, especially muscles, before toxic concentrations can build up. Infusions of MSG are used in mainstream clinical practice to reduce high ammonia levels in the blood (hyperammonemia) by stimulating the conversion of glutamate to glutamine. Both glutamate (as MSG) and glutamine are used by conventional medicine for treating several very serious conditions. Glutamine supplementation has shown better neural energy production and better neuro-transmitter balance are typical results, with improved mental performance and a sense of well-being. The glutamine cycle in the brain is simple and elegant. Glutamine readily crosses the blood-brain barrier. Neurons take up glutamine and convert it to glutamate or GABA (through the step of decarboxylating the glutamate). Some glutamate is used for energy, some for synthesis of glutathione and niacin, some as neurotransmitter."(3.)

"After either glutamate or GABA are released into the synaptic junction, the supportive cells called glia (more specifically, astroglia or astrocytes)--the most abundant type of cell in the central nervous system--with their high supply of glutamine synthase, take up the glutamate or GABA and resynthesize glutamine, detoxifying ammonia in the process. The glutamate that's not converted is used by the glia as a source of energy, and also to produce energy nutrients alanine and alpha-ketoglutarate, which are then released to the neurons. If excess glutamine accumulates through the action of the glia, the brain donates it to the body. Normally, however, the brain, releases very little glutamine, in contrast to muscle and adipose tissue, which donate a lot. During a stroke, ischemic episodes damage the glutamate receptors, so that later the glutamate can't work as a neurotransmitter. Without glutamate, there is no memory and no learning. Glutamate is also deficient in schizophrenia. It's an indispensable neurotransmitter produced in the brain according to need. When the central nervous system is aroused, we don't see higher glucose consumption. Instead, some of the glucose is converted to glutamate. An abundant supply of glutamine makes it easier for the brain to maintain neurotransmitter balance, by increasing the production of glutamate when required for alertness, learning and memory, and the production of GABA when its inhibitory properties are needed."(3.)

"What is the significance of the empty stomach?
Normally the blood-brain barrier protects the brain from excessive
amounts of any single amino acid. However that protection is reduced
dramatically when the amino acid is taken on an empty stomach in
isolation from other amino acids. In fact it is because of the natural
protection of the blood-brain barrier that it is considered necessary
to take glutamine on an empty stomach for purposes of stimulating the
release of growth hormone. If the glutamine is taken as part of
complete proteins, with a meal or on a full stomach, then it will be
forced to compete with other nutrients and amino acids for entrance to
the brain. But that competition between amino acids for entrance to
the brain is the normal state of nature; it ensures that no single
amino acid will flood the brain in isolation. Glutamine works for
stimulating GH release only if we intentionally defeat mother nature's
built-in protections, which in itself is an indication that some risks
are involved."(4.)

"Another concern is that the brain is more vulnerable to excitotoxicity
when the body is fasting. The brain derives most of its energy from
glucose (sugar), and it needs that energy to defend against any sudden
increase in glutamate. The worst time to take large amounts of
glutamine is in the morning before breakfast on an empty stomach, when
the body has been fasting overnight and blood sugar is low."(4.)

(1.) http://www.lef.org/magazine/mag99/sep99-report3.html

(2.) http://biologyofkundalini.com/article.php?story=SupplementList

(3.) Glutamine http://www.tuberose.com/Inflammation_Damage_&_Repair.html

(4.) http://groups.google.com/group/misc.fitness.weights/browse_thread/thread/c86779291cfa2781/a99488e2b334728c%23a99488e2b334728c

--gjh