Gene Association: SLC17A6

L-Glutamic acid

C5H9NO4 (147.0532)

Glutamic acid (Glu), also known as L-glutamic acid or as glutamate, the name of its anion, is an alpha-amino acid. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon). Amino acids are organic compounds that contain amino (‚ÄìNH2) and carboxyl (‚ÄìCOOH) functional groups, along with a side chain (R group) specific to each amino acid. L-glutamic acid is one of 20 proteinogenic amino acids, i.e., the amino acids used in the biosynthesis of proteins. Glutamic acid is found in all organisms ranging from bacteria to plants to animals. It is classified as an acidic, charged (at physiological pH), aliphatic amino acid. In humans it is a non-essential amino acid and can be synthesized via alanine or aspartic acid via alpha-ketoglutarate and the action of various transaminases. Glutamate also plays an important role in the bodys disposal of excess or waste nitrogen. Glutamate undergoes deamination, an oxidative reaction catalysed by glutamate dehydrogenase leading to alpha-ketoglutarate. In many respects glutamate is a key molecule in cellular metabolism. Glutamate is the most abundant fast 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 is 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: Damage to mitochondria from excessively high intracellular Ca2+. 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, and Alzheimers disease. Glutamic acid has been implicated in epileptic seizures. Microinjection of glutamic acid into neurons produces spontaneous depolarization 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 (http://en.wikipedia.org/wiki/Glutamic_acid). Glutamate was discovered in 1866 when it was extracted from wheat gluten (from where it got its name. Glutamate has an important role as a food additive and food flavoring agent. In 1908, Japanese researcher Kikunae Ikeda identified brown crystals left behind after the evaporation of a large amount of kombu broth (a Japanese soup) as glutamic acid. These crystals, when tasted, reproduced a salty, savory flavor detected in many foods, most especially in seaweed. Professor Ikeda termed this flavor umami. He then patented a method of mass-producing a crystalline salt of glutamic acid, monosodium glutamate. L-glutamic acid is an optically active form of glutamic acid having L-configuration. It has a role as a nutraceutical, a micronutrient, an Escherichia coli metabolite, a mouse metabolite, a ferroptosis inducer and a neurotransmitter. It is a glutamine family amino acid, a proteinogenic amino acid, a glutamic acid and a L-alpha-amino acid. It is a conjugate acid of a L-glutamate(1-). It is an enantiomer of a D-glutamic acid. A peptide that is a homopolymer of glutamic acid. L-Glutamic acid is a metabolite found in or produced by Escherichia coli (strain K12, MG1655). Glutamic acid (Glu), also referred to as glutamate (the anion), is one of the 20 proteinogenic amino acids. It is not among the essential amino acids. 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 or other functional roles in the body. Glutamate is the most abundant fast 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 is 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: * Damage to mitochondria from excessively high intracellular Ca2+. * 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, and Alzheimers disease. glutamic acid has been implicated in epileptic seizures. Microinjection of glutamic acid into neurons produces spontaneous depolarization 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. A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM. See also: Monosodium Glutamate (active moiety of); Glatiramer Acetate (monomer of); Glatiramer (monomer of) ... View More ... obtained from acid hydrolysis of proteins. Since 1965 the industrial source of glutamic acid for MSG production has been bacterial fermentation of carbohydrate sources such as molasses and corn starch hydrolysate in the presence of a nitrogen source such as ammonium salts or urea. Annual production approx. 350000t worldwide in 1988. Seasoning additive in food manuf. (as Na, K and NH4 salts). Dietary supplement, nutrient Glutamic acid (symbol Glu or E;[4] the anionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. 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 in the vertebrate nervous system. It serves as the precursor for the synthesis of the inhibitory gamma-aminobutyric acid (GABA) in GABAergic neurons. Its molecular formula is C 5H 9NO 4. Glutamic acid exists in two optically isomeric forms; the dextrorotatory l-form is usually obtained by hydrolysis of gluten or from the waste waters of beet-sugar manufacture or by fermentation.[5][full citation needed] Its molecular structure could be idealized as HOOC−CH(NH 2)−(CH 2)2−COOH, with two carboxyl groups −COOH and one amino group −NH 2. However, in the solid state and mildly acidic water solutions, the molecule assumes an electrically neutral zwitterion structure −OOC−CH(NH+ 3)−(CH 2)2−COOH. It is encoded by the codons GAA or GAG. The acid can lose one proton from its second carboxyl group to form the conjugate base, the singly-negative anion glutamate −OOC−CH(NH+ 3)−(CH 2)2−COO−. This form of the compound is prevalent in neutral solutions. The glutamate neurotransmitter plays the principal role in neural activation.[6] This anion creates the savory umami flavor of foods and is found in glutamate flavorings such as MSG. In Europe, it is classified as food additive E620. In highly alkaline solutions the doubly negative anion −OOC−CH(NH 2)−(CH 2)2−COO− prevails. The radical corresponding to glutamate is called glutamyl. The one-letter symbol E for glutamate was assigned in alphabetical sequence to D for aspartate, being larger by one methylene –CH2– group.[7] DL-Glutamic acid is the conjugate acid of Glutamic acid, which acts as a fundamental metabolite. Comparing with the second phase of polymorphs α and β L-Glutamic acid, DL-Glutamic acid presents better stability[1]. DL-Glutamic acid is the conjugate acid of Glutamic acid, which acts as a fundamental metabolite. Comparing with the second phase of polymorphs α and β L-Glutamic acid, DL-Glutamic acid presents better stability[1]. L-Glutamic acid acts as an excitatory transmitter and an agonist at all subtypes of glutamate receptors (metabotropic, kainate, NMDA, and AMPA). L-Glutamic acid shows a direct activating effect on the release of DA from dopaminergic terminals. L-Glutamic acid is an excitatory amino acid neurotransmitter that acts as an agonist for all subtypes of glutamate receptors (metabolic rhodophylline, NMDA, and AMPA). L-Glutamic acid has an agonist effect on the release of DA from dopaminergic nerve endings. L-Glutamic acid can be used in the study of neurological diseases[1][2][3][4][5]. L-Glutamic acid acts as an excitatory transmitter and an agonist at all subtypes of glutamate receptors (metabotropic, kainate, NMDA, and AMPA). L-Glutamic acid shows a direct activating effect on the release of DA from dopaminergic terminals.

Kynurenic acid

C10H7NO3 (189.0426)

Kynurenic acid is a quinolinemonocarboxylic acid that is quinoline-2-carboxylic acid substituted by a hydroxy group at C-4. It has a role as a G-protein-coupled receptor agonist, a NMDA receptor antagonist, a nicotinic antagonist, a neuroprotective agent, a human metabolite and a Saccharomyces cerevisiae metabolite. It is a monohydroxyquinoline and a quinolinemonocarboxylic acid. It is a conjugate acid of a kynurenate. Kynurenic Acid is under investigation in clinical trial NCT02340325 (FS2 Safety and Tolerability Study in Healthy Volunteers). Kynurenic acid is a natural product found in Ephedra foeminea, Ephedra intermedia, and other organisms with data available. Kynurenic acid is a uremic toxin. Uremic toxins can be subdivided into three major groups based upon their chemical and physical characteristics: 1) small, water-soluble, non-protein-bound compounds, such as urea; 2) small, lipid-soluble and/or protein-bound compounds, such as the phenols and 3) larger so-called middle-molecules, such as beta2-microglobulin. Chronic exposure of uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease. Kynurenic acid (KYNA) is a well-known endogenous antagonist of the glutamate ionotropic excitatory amino acid receptors N-methyl-D-aspartate (NMDA), alphaamino-3-hydroxy-5-methylisoxazole-4-propionic acid and kainate receptors and of the nicotine cholinergic subtype alpha 7 receptors. KYNA neuroprotective and anticonvulsive activities have been demonstrated in animal models of neurodegenerative diseases. Because of KYNAs neuromodulatory character, its involvement has been speculatively linked to the pathogenesis of a number of neurological conditions including those in the ageing process. Different patterns of abnormalities in various stages of KYNA metabolism in the CNS have been reported in Alzheimers disease, Parkinsons disease and Huntingtons disease. In HIV-1-infected patients and in patients with Lyme neuroborreliosis a marked rise of KYNA metabolism was seen. In the ageing process KYNA metabolism in the CNS of rats shows a characteristic pattern of changes throughout the life span. A marked increase of the KYNA content in the CNS occurs before the birth, followed by a dramatic decline on the day of birth. A low activity was seen during ontogenesis, and a slow and progressive enhancement occurs during maturation and ageing. This remarkable profile of KYNA metabolism alterations in the mammalian brain has been suggested to result from the development of the organisation of neuronal connections and synaptic plasticity, development of receptor recognition sites, maturation and ageing. There is significant evidence that KYNA can improve cognition and memory, but it has also been demonstrated that it interferes with working memory. Impairment of cognitive function in various neurodegenerative disorders is accompanied by profound reduction and/or elevation of KYNA metabolism. The view that enhancement of CNS KYNA levels could underlie cognitive decline is supported by the increased KYNA metabolism in Alzheimers disease, by the increased KYNA metabolism in downs syndrome and the enhancement of KYNA function during the early stage of Huntingtons disease. Kynurenic acid is the only endogenous N-methyl-D-aspartate (NMDA) receptor antagonist identified up to now, that mediates glutamatergic hypofunction. Schizophrenia is a disorder of dopaminergic neurotransmission, but modulation of the dopaminergic system by glutamatergic neurotransmission seems to play a key role. Despite the NMDA receptor antagonism, kynurenic acid also blocks, in lower doses, the nicotinergic acetycholine receptor, i.e., increased kynurenic acid levels can explain psychotic symptoms and cognitive deterioration. Kynurenic acid levels are described to be higher in the cerebrospinal fluid (CSF) and in critical central nervous system (CNS) regions of schizophrenics as compared to controls. (A3279, A3280).... Kynurenic acid (KYNA) is a well-known endogenous antagonist of the glutamate ionotropic excitatory amino acid receptors N-methyl-D-aspartate (NMDA), alphaamino-3-hydroxy-5-methylisoxazole-4-propionic acid and kainate receptors and of the nicotine cholinergic subtype alpha 7 receptors. KYNA neuroprotective and anticonvulsive activities have been demonstrated in animal models of neurodegenerative diseases. Because of KYNAs neuromodulatory character, its involvement has been speculatively linked to the pathogenesis of a number of neurological conditions including those in the ageing process. Different patterns of abnormalities in various stages of KYNA metabolism in the CNS have been reported in Alzheimers disease, Parkinsons disease and Huntingtons disease. In HIV-1-infected patients and in patients with Lyme neuroborreliosis a marked rise of KYNA metabolism was seen. In the ageing process KYNA metabolism in the CNS of rats shows a characteristic pattern of changes throughout the life span. A marked increase of the KYNA content in the CNS occurs before the birth, followed by a dramatic decline on the day of birth. A low activity was seen during ontogenesis, and a slow and progressive enhancement occurs during maturation and ageing. This remarkable profile of KYNA metabolism alterations in the mammalian brain has been suggested to result from the development of the organisation of neuronal connections and synaptic plasticity, development of receptor recognition sites, maturation and ageing. There is significant evidence that KYNA can improve cognition and memory, but it has also been demonstrated that it interferes with working memory. Impairment of cognitive function in various neurodegenerative disorders is accompanied by profound reduction and/or elevation of KYNA metabolism. The view that enhancement of CNS KYNA levels could underlie cognitive decline is supported by the increased KYNA metabolism in Alzheimers disease, by the increased KYNA metabolism in downs syndrome and the enhancement of KYNA function during the early stage of Huntingtons disease. Kynurenic acid is the only endogenous N-methyl-D-aspartate (NMDA) receptor antagonist identified up to now, that mediates glutamatergic hypofunction. Schizophrenia is a disorder of dopaminergic neurotransmission, but modulation of the dopaminergic system by glutamatergic neurotransmission seems to play a key role. Despite the NMDA receptor antagonism, kynurenic acid also blocks, in lower doses, the nicotinergic acetycholine receptor, i.e., increased kynurenic acid levels can explain psychotic symptoms and cognitive deterioration. Kynurenic acid levels are described to be higher in the cerebrospinal fluid (CSF) and in critical central nervous system (CNS) regions of schizophrenics as compared to controls. (PMID: 17062375 , 16088227). KYNA has also been identified as a uremic toxin according to the European Uremic Toxin Working Group (PMID: 22626821). Kynurenic acid (KYNA) is a well-known endogenous antagonist of the glutamate ionotropic excitatory amino acid receptors N-methyl-D-aspartate (NMDA), alphaamino-3-hydroxy-5-methylisoxazole-4-propionic acid and kainate receptors and of the nicotine cholinergic subtype alpha 7 receptors. KYNA neuroprotective and anticonvulsive activities have been demonstrated in animal models of neurodegenerative diseases. Because of KYNAs neuromodulatory character, its involvement has been speculatively linked to the pathogenesis of a number of neurological conditions including those in the ageing process. Different patterns of abnormalities in various stages of KYNA metabolism in the CNS have been reported in Alzheimers disease, Parkinsons disease and Huntingtons disease. In HIV-1-infected patients and in patients with Lyme neuroborreliosis a marked rise of KYNA metabolism was seen. In the ageing process KYNA metabolism in the CNS of rats shows a characteristic pattern of changes throughout the life span. A marked increase of the KYNA content in the CNS occurs before the birth, followed by a dramatic decline on the day of birth. A low activity was seen during ontogenesis, and a slow and progressive enhancement occurs during maturation and ageing. This remarkable profile of KYNA metabolism alterations in the mammalian brain has been suggested to result from the development of the organisation of neuronal connections and synaptic plasticity, development of receptor recognition sites, maturation and ageing. There is significant evidence that KYNA can improve cognition and memory, but it has also been demonstrated that it interferes with working memory. Impairment of cognitive function in various neurodegenerative disorders is accompanied by profound reduction and/or elevation of KYNA metabolism. The view that enhancement of CNS KYNA levels could underlie cognitive decline is supported by the increased KYNA metabolism in Alzheimers disease, by the increased KYNA metabolism in downs syndrome and the enhancement of KYNA function during the early stage of Huntingtons disease. Kynurenic acid is the only endogenous N-methyl-D-aspartate (NMDA) receptor antagonist identified up to now, that mediates glutamatergic hypofunction. Schizophrenia is a disorder of dopaminergic neurotransmission, but modulation of the dopaminergic system by glutamatergic neurotransmission seems to play a key role. Despite the NMDA receptor antagonism, kynurenic acid also blocks, in lower doses, the nicotinergic acetycholine receptor, i.e., increased kynurenic acid levels can explain psychotic symptoms and cognitive deterioration. Kynurenic acid levels are described to be higher in the cerebrospinal fluid (CSF) and in critical central nervous system (CNS) regions of schizophrenics as compared to controls. (PMID: 17062375, 16088227) [HMDB] D018377 - Neurotransmitter Agents > D018683 - Excitatory Amino Acid Agents > D018691 - Excitatory Amino Acid Antagonists A quinolinemonocarboxylic acid that is quinoline-2-carboxylic acid substituted by a hydroxy group at C-4. [Raw Data] CBA11_Kynurenic-acid_pos_30eV_1-3_01_673.txt [Raw Data] CBA11_Kynurenic-acid_pos_50eV_1-3_01_675.txt [Raw Data] CBA11_Kynurenic-acid_pos_40eV_1-3_01_674.txt [Raw Data] CBA11_Kynurenic-acid_neg_30eV_1-3_01_726.txt [Raw Data] CBA11_Kynurenic-acid_pos_20eV_1-3_01_672.txt [Raw Data] CBA11_Kynurenic-acid_pos_10eV_1-3_01_671.txt [Raw Data] CBA11_Kynurenic-acid_neg_20eV_1-3_01_725.txt [Raw Data] CBA11_Kynurenic-acid_neg_50eV_1-3_01_728.txt [Raw Data] CBA11_Kynurenic-acid_neg_40eV_1-3_01_727.txt [Raw Data] CBA11_Kynurenic-acid_neg_10eV_1-3_01_724.txt Kynurenic acid, an endogenous tryptophan metabolite, is a broad-spectrum antagonist targeting NMDA, glutamate, α7 nicotinic acetylcholine receptor. Kynurenic acid is also an agonist of GPR35/CXCR8.

(RS)-3,5-DHPG

C8H9NO4 (183.0532)

D018377 - Neurotransmitter Agents > D018683 - Excitatory Amino Acid Agents > D018691 - Excitatory Amino Acid Antagonists D018377 - Neurotransmitter Agents > D018683 - Excitatory Amino Acid Agents > D018690 - Excitatory Amino Acid Agonists DHPG ((RS)-3,5-DHPG) is an amino acid, which acts as a selective and potent agonist of group I mGluR (mGluR 1 and mGluR 5), shows no effect on Group II or Group III mGluRs[1]. DHPG ((RS)-3,5-DHPG) is also an effective antagonist of mGluRs linked to phospholipase D[2].

Ergocornin

C31H39N5O5 (561.2951)

γ-Aminobutyric acid

C4H9NO2 (103.0633)

gamma-Aminobutyric acid (GABA) is an inhibitory neurotransmitter found in the nervous systems of widely divergent species, including humans. It is the chief inhibitory neurotransmitter in the vertebrate central nervous system. In vertebrates, GABA acts at inhibitory synapses in the brain. It acts by binding to specific transmembrane receptors in the plasma membrane of both pre- and postsynaptic neurons. This binding causes the opening of ion channels to allow either the flow of negatively-charged chloride ions into the cell or positively-charged potassium ions out of the cell. This will typically result in a negative change in the transmembrane potential, usually causing hyperpolarization. Three general classes of GABA receptor are known (PMID: 10561820). These include GABA-A and GABA-C ionotropic receptors, which are ion channels themselves, and GABA-B metabotropic receptors, which are G protein-coupled receptors that open ion channels via intermediaries known as G proteins (PMID: 10561820). Activation of the GABA-B receptor by GABA causes neuronal membrane hyperpolarization and a resultant inhibition of neurotransmitter release. In addition to binding sites for GABA, the GABA-A receptor has binding sites for benzodiazepines, barbiturates, and neurosteroids. GABA-A receptors are coupled to chloride ion channels. Therefore, activation of the GABA-A receptor induces increased inward chloride ion flux, resulting in membrane hyperpolarization and neuronal inhibition (PMID: 10561820). After release into the synapse, free GABA that does not bind to either the GABA-A or GABA-B receptor complexes can be taken up by neurons and glial cells. Four different GABA membrane transporter proteins (GAT-1, GAT-2, GAT-3, and BGT-1), which differ in their distribution in the CNS, are believed to mediate the uptake of synaptic GABA into neurons and glial cells. The GABA-A receptor subtype regulates neuronal excitability and rapid changes in fear arousal, such as anxiety, panic, and the acute stress response (PMID: 10561820). Drugs that stimulate GABA-A receptors, such as the benzodiazepines and barbiturates, have anxiolytic and anti-seizure effects via GABA-A-mediated reduction of neuronal excitability, which effectively raises the seizure threshold. GABA-A antagonists produce convulsions in animals and there is decreased GABA-A receptor binding in a positron emission tomography (PET) study of patients with panic disorder. Neurons that produce GABA as their output are called GABAergic neurons and have chiefly inhibitory action at receptors in the vertebrate. Medium spiny neurons (MSNs) are a typical example of inhibitory CNS GABAergic cells. GABA has been shown to have excitatory roles in the vertebrate, most notably in the developing cortex. Organisms synthesize GABA from glutamate using the enzyme L-glutamic acid decarboxylase and pyridoxal phosphate as a cofactor (PMID: 12467378). It is worth noting that this involves converting the principal excitatory neurotransmitter (glutamate) into the principal inhibitory one (GABA). Drugs that act as agonists of GABA receptors (known as GABA analogs or GABAergic drugs), or increase the available amount of GABA typically have relaxing, anti-anxiety, and anti-convulsive effects. GABA is found to be deficient in cerebrospinal fluid and the brain in many studies of experimental and human epilepsy. Benzodiazepines (such as Valium) are useful in status epilepticus because they act on GABA receptors. GABA increases in the brain after administration of many seizure medications. Hence, GABA is clearly an antiepileptic nutrient. Inhibitors of GAM metabolism can also produce convulsions. Spasticity and involuntary movement syndromes, such as Parkinsons, Friedreichs ataxia, tardive dyskinesia, and Huntingtons chorea, are all marked by low GABA when amino acid levels are studied. Trials of 2 to 3 g of GABA given orally have been effective in various epilepsy and spasticity syndromes. Agents that elevate GABA are als... Gamma-aminobutyric acid, also known as gaba or 4-aminobutanoic acid, belongs to gamma amino acids and derivatives class of compounds. Those are amino acids having a (-NH2) group attached to the gamma carbon atom. Thus, gamma-aminobutyric acid is considered to be a fatty acid lipid molecule. Gamma-aminobutyric acid is soluble (in water) and a weakly acidic compound (based on its pKa). Gamma-aminobutyric acid can be synthesized from butyric acid. Gamma-aminobutyric acid is also a parent compound for other transformation products, including but not limited to, (1S,2S,5S)-2-(4-glutaridylbenzyl)-5-phenylcyclohexan-1-ol, 4-(methylamino)butyric acid, and pregabalin. Gamma-aminobutyric acid can be found in a number of food items such as watercress, sour cherry, peach, and cardoon, which makes gamma-aminobutyric acid a potential biomarker for the consumption of these food products. Gamma-aminobutyric acid can be found primarily in most biofluids, including urine, cerebrospinal fluid (CSF), blood, and feces, as well as throughout most human tissues. Gamma-aminobutyric acid exists in all living species, ranging from bacteria to humans. In humans, gamma-aminobutyric acid is involved in a couple of metabolic pathways, which include glutamate metabolism and homocarnosinosis. Gamma-aminobutyric acid is also involved in few metabolic disorders, which include 2-hydroxyglutric aciduria (D and L form), 4-hydroxybutyric aciduria/succinic semialdehyde dehydrogenase deficiency, hyperinsulinism-hyperammonemia syndrome, and succinic semialdehyde dehydrogenase deficiency. Moreover, gamma-aminobutyric acid is found to be associated with alzheimers disease, hyper beta-alaninemia, tuberculous meningitis, and hepatic encephalopathy. Gamma-aminobutyric acid is a non-carcinogenic (not listed by IARC) potentially toxic compound. gamma-Aminobutyric acid (γ-Aminobutyric acid) (GABA ) is the chief inhibitory neurotransmitter in the mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. In humans, GABA is also directly responsible for the regulation of muscle tone . Chronically high levels of GABA are associated with at least 5 inborn errors of metabolism including: D-2-Hydroxyglutaric Aciduria, 4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency, GABA-Transaminase Deficiency, Homocarnosinosis and Succinic semialdehyde dehydrogenase deficiency (T3DB). [Spectral] 4-Aminobutanoate (exact mass = 103.06333) and D-2-Aminobutyrate (exact mass = 103.06333) were not completely separated on HPLC under the present analytical conditions as described in AC$XXX. Additionally some of the peaks in this data contains dimers and other unidentified ions. Acquisition and generation of the data is financially supported in part by CREST/JST. COVID info from clinicaltrial, clinicaltrials, clinical trial, clinical trials D018377 - Neurotransmitter Agents > D018682 - GABA Agents KEIO_ID A002 Corona-virus Coronavirus SARS-CoV-2 COVID-19 SARS-CoV COVID19 SARS2 SARS γ-Aminobutyric acid (4-Aminobutyric acid) is a major inhibitory neurotransmitter in the adult mammalian brain, binding to the ionotropic GABA receptors (GABAA receptors) and metabotropic receptors (GABAB receptors. γ-Aminobutyric acid shows calming effect by blocking specific signals of central nervous system[1][2]. γ-Aminobutyric acid (4-Aminobutyric acid) is a major inhibitory neurotransmitter in the adult mammalian brain, binding to the ionotropic GABA receptors (GABAA receptors) and metabotropic receptors (GABAB receptors. γ-Aminobutyric acid shows calming effect by blocking specific signals of central nervous system[1][2]. γ-Aminobutyric acid (4-Aminobutyric acid) is a major inhibitory neurotransmitter in the adult mammalian brain, binding to the ionotropic GABA receptors (GABAA receptors) and metabotropic receptors (GABAB receptors. γ-Aminobutyric acid shows calming effect by blocking specific signals of central nervous system[1][2].

Tetrahydrocannabinol

C21H30O2 (314.2246)

Tetrahydrocannabinol, abbreviated THC, is a cannabinoid identified in cannabis and is its principal psychoactive constituent. First isolated in 1964, in its pure form, it is a glassy solid when cold, and becomes viscous and sticky if warmed. Synthetically prepared THC, officially referred to by its INN, dronabinol, is available by prescription in the U.S. and Canada under the brand name Marinol. The mechanism of action of THC is not completely understood. It is thought that cannabinoid receptors in neural tissues may mediate the effects of cannabinoids. Animal studies suggest that Marinols antiemetic effects may be due to inhibition of the vomiting control mechanism in the medulla oblongata. A literature review on the subject concluded that "Cannabis use appears to be neither a sufficient nor a necessary cause for psychosis. It is a component cause, part of a complex constellation of factors leading to psychosis." Likewise, a French review from 2009 came to a conclusion that cannabis use, particularly that before age 15, was a factor in the development of schizophrenic disorders. An aromatic terpenoid, THC has a very low solubility in water, but good solubility in most organic solvents, specifically lipids and alcohols. The presence of these specialized cannabinoid receptors in the brain led researchers to the discovery of endocannabinoids, such as anandamide and 2-arachidonoyl glyceride (2-AG). THC targets receptors in a manner far less selective than endocannabinoid molecules released during retrograde signalling, as the drug has a relatively low cannabinoid receptor efficacy and affinity. In populations of low cannabinoid receptor density, THC may act to antagonize endogenous agonists that possess greater receptor efficacy. THC is a lipophilic molecule and may bind non-specifically to a variety of receptors in the brain and body, such as adipose tissue. Dronabinol is only found in individuals that have used or taken this drug. It is extracted from the resin of Cannabis sativa (marijuana, hashish). The isomer delta-9-tetrahydrocannabinol is considered the most active form, producing the characteristic mood and perceptual changes associated with this compound. In the United States, Marinol has been rescheduled from Schedule II to Schedule III of the Controlled Substances Act in 1999, reflecting a finding that THC had a potential for abuse less than that of cocaine and heroin. As a Schedule III drug, it is available by prescription and is considered to be non-narcotic and to have a low risk of physical or mental dependence. Marinol has been approved by the U.S. Food and Drug Administration (FDA) in the treatment of anorexia in AIDS patients, as well as for refractory nausea and vomiting of patients undergoing chemotherapy, which has raised much controversy as to why natural THC is still a Schedule I drug. Efforts to get cannabis rescheduled as analogous to Marinol have not succeeded thus far. In April 2005, Canadian authorities approved the marketing of Sativex, a mouth spray for multiple sclerosis patients, who can use it to alleviate neuropathic pain and spasticity. Sativex contains tetrahydrocannabinol together with cannabidiol and is a preparation of whole cannabis rather than individual cannabinoids. It is marketed in Canada by GW Pharmaceuticals, being the first cannabis-based prescription drug in the world (in modern times). In addition, Sativex received European regulatory approval in 2010. An analog of dronabinol, nabilone, is available commercially in Canada under the trade name Cesamet, manufactured by Valeant Pharmaceuticals. Cesamet has also received FDA approval and began marketing in the U.S. in 2006. It is a Schedule II drug. Δ9tetrahydrocannabinol, also known as delta(9)-thc or marinol, is a member of the class of compounds known as 2,2-dimethyl-1-benzopyrans. 2,2-dimethyl-1-benzopyrans are organic compounds containing a 1-benzopyran moiety that carries two methyl groups at the 2-position. Δ9tetrahydrocannabinol is practically insoluble (in water) and a very weakly acidic compound (based on its pKa). Δ9tetrahydrocannabinol can be found in a number of food items such as wakame, cloves, burbot, and black cabbage, which makes Δ9tetrahydrocannabinol a potential biomarker for the consumption of these food products. Δ9tetrahydrocannabinol can be found primarily in blood and urine. Δ9tetrahydrocannabinol is a non-carcinogenic (not listed by IARC) potentially toxic compound. Δ9tetrahydrocannabinol is a drug which is used for the treatment of anorexia associated with weight loss in patients with aids, and nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatment. The mechanism of action of marinol is not completely understood. It is thought that cannabinoid receptors in neural tissues may mediate the effects of dronabinol and other cannabinoids. Animal studies with other cannabinoids suggest that marinols antiemetic effects may be due to inhibition of the vomiting control mechanism in the medulla oblongata (DrugBank). A potentially serious oral ingestion, if recent, should be managed with gut decontamination. In unconscious patients with a secure airway, instill activated charcoal (30 to 100 g in adults, 1 to 2 g/kg in infants) via a nasogastric tube. A saline cathartic or sorbitol may be added to the first dose of activated charcoal. Patients experiencing depressive, hallucinatory or psychotic reactions should be placed in a quiet area and offered reassurance. Benzodiazepines (5 to 10 mg diazepam po) may be used for treatment of extreme agitation. Hypotension usually responds to Trendelenburg position and IV fluids. Pressors are rarely required (L1712) (T3DB). D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006728 - Hormones > D063385 - Cannabinoid Receptor Modulators D018377 - Neurotransmitter Agents > D063385 - Cannabinoid Receptor Modulators > D063386 - Cannabinoid Receptor Agonists A - Alimentary tract and metabolism > A04 - Antiemetics and antinauseants > A04A - Antiemetics and antinauseants D002491 - Central Nervous System Agents > D011619 - Psychotropic Drugs > D006213 - Hallucinogens D018373 - Peripheral Nervous System Agents > D018689 - Sensory System Agents C78272 - Agent Affecting Nervous System > C267 - Antiemetic Agent D002491 - Central Nervous System Agents > D000700 - Analgesics

Methionine sulfoximine

C5H12N2O3S (180.0569)

Methionine sulfoximine is found in flours treated with NCl3 as a produced of NCl3 action on wheat protein

Muscimol

C4H6N2O2 (114.0429)

D018377 - Neurotransmitter Agents > D018682 - GABA Agents > D018755 - GABA Agonists D009676 - Noxae > D011042 - Poisons > D009183 - Mycotoxins KEIO_ID M115

Biotin amide

C10H17N3O2S (243.1041)

The enzyme biotinidase (EC-Number 3.5.1.12 ) is involved in the recycling of the vitamin biotin, cleaving D-biotinylamides and esters, in a reaction including biotin amide and water. (PMID 1719240, 171927). Late-onset multiple carboxylase deficiency (MCD) with biotinidase deficiency is caused by mutation in the biotinidase gene. MCD is an autosomal recessive metabolic disorder characterized primarily by cutaneous and neurologic abnormalities. Symptoms result from the patients inability to reutilize biotin, a necessary nutrient. (OMIM 253260). The enzyme biotinidase (EC-Number 3.5.1.12 ) is involved in the recycling of the vitamin biotin, cleaving D-biotinylamides and esters, in a reaction including biotin amide and water. (PMID 1719240, 171927)

Imidazoleacetic acid ribotide

C10H15N2O9P (338.0515)

Imidazoleacetic acid ribotide (IAA-RP ) is an endogenous ligand that stimulates imidazol(in)e receptors. Experimental data suggest that IAA-RP may participate in transsynaptic signaling in brain, because it exists in brainstem neurons, exhibits depolarization-induced Ca2+-dependent release from P2 synaptosomal elements, has relatively high affinity for membrane-bound I-R sites, and produces physiological effects on exogenous application. IAA-RP is rapidly metabolized by phosphatases and ecto-5-nucleotidases. (PMID: 15365189) [HMDB] Imidazoleacetic acid ribotide (IAA-RP) is an endogenous ligand that stimulates imidazol(in)e receptors. Experimental data suggest that IAA-RP may participate in transsynaptic signaling in brain, because it exists in brainstem neurons, exhibits depolarization-induced Ca2+-dependent release from P2 synaptosomal elements, has relatively high affinity for membrane-bound I-R sites, and produces physiological effects on exogenous application. IAA-RP is rapidly metabolized by phosphatases and ecto-5-nucleotidases. (PMID: 15365189).

2517-07-9

C6H9NO2 (127.0633)

Cyclothiazide

C14H16ClN3O4S2 (389.0271)

As a diuretic, cyclothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like cyclothiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of cyclothiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle. Cyclothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension. C - Cardiovascular system > C03 - Diuretics > C03A - Low-ceiling diuretics, thiazides > C03AA - Thiazides, plain C78275 - Agent Affecting Blood or Body Fluid > C448 - Diuretic > C49185 - Thiazide Diuretic D002317 - Cardiovascular Agents > D000959 - Antihypertensive Agents D002317 - Cardiovascular Agents > D045283 - Natriuretic Agents D045283 - Natriuretic Agents > D004232 - Diuretics Same as: D01256 Cyclothiazide, a positive allosteric modulator of AMPA receptors, is used frequently to block the desensitization of both native and heterologously expressed AMPA receptors. Cyclothiazide is known to produce a fast inhibition of AMPA receptor desensitization and a much slower potentiation of the AMPA current[1].

alpha-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC ACID

C7H10N2O4 (186.0641)

D018377 - Neurotransmitter Agents > D018683 - Excitatory Amino Acid Agents > D018690 - Excitatory Amino Acid Agonists (RS)-AMPA ((±)-AMPA) is a glutamate analogue and a potent and selective excitatory neurotransmitter L-glutamic acid agonist. (RS)-AMPA does not interfere with binding sites for kainic acid or NMDA receptors[1][2].

Tetrahydrodeoxycorticosterone

C21H34O3 (334.2508)

The neurosteroid allotetrahydrodeoxycorticosterone (THDOC) is an allosteric modulator of the GABA(A) receptor. Although the role of THDOC within the brain is undefined, recent studies indicate that stress induces THDOC to levels that can activate GABA(A) receptors. These results might have significant implications for human stress-sensitive conditions such as epilepsy, post-traumatic stress disorder and depression. (PMID 12628349) [HMDB] The neurosteroid allotetrahydrodeoxycorticosterone (THDOC) is an allosteric modulator of the GABA(A) receptor. Although the role of THDOC within the brain is undefined, recent studies indicate that stress induces THDOC to levels that can activate GABA(A) receptors. These results might have significant implications for human stress-sensitive conditions such as epilepsy, post-traumatic stress disorder and depression. (PMID 12628349). D002491 - Central Nervous System Agents > D002492 - Central Nervous System Depressants > D000777 - Anesthetics D002492 - Central Nervous System Depressants > D014149 - Tranquilizing Agents > D014151 - Anti-Anxiety Agents D002491 - Central Nervous System Agents > D011619 - Psychotropic Drugs > D014149 - Tranquilizing Agents D006730 - Hormones, Hormone Substitutes, and Hormone Antagonists > D006728 - Hormones D018377 - Neurotransmitter Agents > D000081227 - Neurosteroids 3α,21-Dihydroxy-5α-pregnan-20-one (THDOC), an endogenous neurosteroid, is a positive modulator of GABAA receptors. 3α,21-Dihydroxy-5α-pregnan-20-one potentiates neuronal response to low concentrations of GABA at α4β1δ GABAA receptors in vitro.

Gabazine

C15H17N3O3 (287.127)

D018377 - Neurotransmitter Agents > D018682 - GABA Agents > D018756 - GABA Antagonists

Neuromedin K

C55H79N13O14S2 (1209.5311)

D018377 - Neurotransmitter Agents > D015320 - Tachykinins

DL-Glutamate

C5H9NO4 (147.0532)

DL-Glutamate, also known as E or DL-glutamic acid, belongs to the class of organic compounds known as glutamic acid and derivatives. Glutamic acid and derivatives are compounds containing glutamic acid or a derivative thereof resulting from reaction of glutamic acid at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon). DL-Glutamate exists in all living organisms, ranging from bacteria to humans. DL-Glutamate is found, on average, in the highest concentration within a few different foods, such as red bell peppers, milk (cow), and wheats and in a lower concentration in eggplants, romaine lettuces, and nanking cherries. DL-Glutamate has also been detected, but not quantified, in a few different foods, such as apples, broccoli, and lettuces. Glutamic acid (abbreviated as Glu or E) is one of the 20 proteinogenic amino acids. It is a non-essential amino acid. Glutamic acid is found in many foods, some of which are garden onion, orange bell pepper, oat, and cucumber. D018377 - Neurotransmitter Agents > D018846 - Excitatory Amino Acids DL-Glutamic acid is the conjugate acid of Glutamic acid, which acts as a fundamental metabolite. Comparing with the second phase of polymorphs α and β L-Glutamic acid, DL-Glutamic acid presents better stability[1]. DL-Glutamic acid is the conjugate acid of Glutamic acid, which acts as a fundamental metabolite. Comparing with the second phase of polymorphs α and β L-Glutamic acid, DL-Glutamic acid presents better stability[1].

3,5-Dihydroxyphenylglycine

C8H9NO4 (183.0532)

D018377 - Neurotransmitter Agents > D018683 - Excitatory Amino Acid Agents > D018691 - Excitatory Amino Acid Antagonists D018377 - Neurotransmitter Agents > D018683 - Excitatory Amino Acid Agents > D018690 - Excitatory Amino Acid Agonists DHPG ((RS)-3,5-DHPG) is an amino acid, which acts as a selective and potent agonist of group I mGluR (mGluR 1 and mGluR 5), shows no effect on Group II or Group III mGluRs[1]. DHPG ((RS)-3,5-DHPG) is also an effective antagonist of mGluRs linked to phospholipase D[2].

Kynurenic acid

C10H7NO3 (189.0426)

MS2 deconvoluted using MS2Dec from all ion fragmentation data, MetaboLights identifier MTBLS1040; HCZHHEIFKROPDY-UHFFFAOYSA-N_STSL_0005_Kynurenic acid_2000fmol_180410_S2_LC02_MS02_66; Spectrum acquired as described in Naz et al 2017 PMID 28641411. Preparation and submission to MassBank of North America by Chaleckis R. and Tada I. MS2 deconvoluted using CorrDec from all ion fragmentation data, MetaboLights identifier MTBLS1040; Spectrum acquired as described in Naz et al 2017 PMID 28641411. Preparation and submission to MassBank of North America by Chaleckis R. and Tada I. D018377 - Neurotransmitter Agents > D018683 - Excitatory Amino Acid Agents > D018691 - Excitatory Amino Acid Antagonists relative retention time with respect to 9-anthracene Carboxylic Acid is 0.374 relative retention time with respect to 9-anthracene Carboxylic Acid is 0.376 relative retention time with respect to 9-anthracene Carboxylic Acid is 0.370 relative retention time with respect to 9-anthracene Carboxylic Acid is 0.372 Kynurenic acid, an endogenous tryptophan metabolite, is a broad-spectrum antagonist targeting NMDA, glutamate, α7 nicotinic acetylcholine receptor. Kynurenic acid is also an agonist of GPR35/CXCR8. Kynurenic acid, an endogenous tryptophan metabolite, is a broad-spectrum antagonist targeting NMDA, glutamate, α7 nicotinic acetylcholine receptor. Kynurenic acid is also an agonist of GPR35/CXCR8. Kynurenic acid, an endogenous tryptophan metabolite, is a broad-spectrum antagonist targeting NMDA, glutamate, α7 nicotinic acetylcholine receptor. Kynurenic acid is also an agonist of GPR35/CXCR8. Transtorine is a quinoline alkaloid, found from Ephedra transitoria, with antibacterial activity[1]. Transtorine is a quinoline alkaloid, found from Ephedra transitoria, with antibacterial activity[1].