118661PathwayMemantine Action PathwayMemantine is an N-methyl-D-aspartate (NMDA) receptor antagonist, also know by the brand names Axura, Ebixa, Marixino, Namenda, Namenda 49 Titration Pack, and Namzaric, which is used to treat and manage moderate to severe dementia. Glutamate is a neurotransmitter in the brain that leads to neuronal excitabiity and excessive stimulation in Alzheimer's Disease, so the inhibition of it helps with Alzheimer's Disease. Memantine has also shown minimal activity for GABA, benzodiazepine, dopamine, adrenergic, histamine, and glycine receptors. It has also shwon minimal activity on voltage-dependent Ca2+, Na+, or K+ channels.
Memantine inhibits the influx of calcium caused by chronic NMDA receptor activation by glutamate. The Memantine binds to NMDA receptors, which prevents glutamate from activating the receptor which further prevents the influx of calcium. This leads to an improvement of Alzheimer's dementia symptoms, such as increased cognition. At lower concentrations, often used in clinical settings, it can also enhance neuronal synaptic plasticity in the brain, improve memory, and act as a neuroprotectant against the destruction of neurons.
Despite the antagonistic effects against NMDA receptors, Memantine has not been proven to prevent or retard the neurodegeneration seen in patients diagnosed with Alzheimer's disease. It only treats symptoms of Alzheimer's disease.Drug ActionPW127790CenterPathwayVisualizationContext12806623503500#000099PathwayVisualization118496118661Memantine PathwayMemantine is an N-methyl-D-aspartate (NMDA) receptor antagonist, also know by the brand names Axura, Ebixa, Marixino, Namenda, Namenda 49 Titration Pack, and Namzaric, which is used to treat and manage moderate to severe dementia. Glutamate is a neurotransmitter in the brain that leads to neuronal excitabiity and excessive stimulation in Alzheimer's Disease, so the inhibition of it helps with Alzheimer's Disease. Memantine has also shown minimal activity for GABA, benzodiazepine, dopamine, adrenergic, histamine, and glycine receptors. It has also shwon minimal activity on voltage-dependent Ca2+, Na+, or K+ channels.
Memantine inhibits the influx of calcium caused by chronic NMDA receptor activation by glutamate. The Memantine binds to NMDA receptors, which prevents glutamate from activating the receptor which further prevents the influx of calcium. This leads to an improvement of Alzheimer's dementia symptoms, such as increased cognition. At lower concentrations, often used in clinical settings, it can also enhance neuronal synaptic plasticity in the brain, improve memory, and act as a neuroprotectant against the destruction of neurons.
Despite the antagonistic effects against NMDA receptors, Memantine has not been proven to prevent or retard the neurodegeneration seen in patients diagnosed with Alzheimer's disease. It only treats symptoms of Alzheimer's disease.Drug1120171DepolarizationSubPathway122474353Compound7891201737SubPathway122476500Compound78934128610029935Cacabelos R, Takeda M, Winblad B: The glutamatergic system and neurodegeneration in dementia: preventive strategies in Alzheimer's disease. Int J Geriatr Psychiatry. 1999 Jan;14(1):3-47. doi: 10.1002/(sici)1099-1166(199901)14:1<3::aid-gps897>3.0.co;2-7.118661Pathway34128714530799Rogawski MA, Wenk GL: The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease. CNS Drug Rev. 2003 Fall;9(3):275-308. doi: 10.1111/j.1527-3458.2003.tb00254.x.118661Pathway34128816906789Robinson DM, Keating GM: Memantine: a review of its use in Alzheimer's disease. Drugs. 2006;66(11):1515-34. doi: 10.2165/00003495-200666110-00015.118661Pathway34128911026482Rogawski MA: Low affinity channel blocking (uncompetitive) NMDA receptor antagonists as therapeutic agents--toward an understanding of their favorable tolerability. Amino Acids. 2000;19(1):133-49. doi: 10.1007/s007260070042.118661Pathway34129011403963118661Pathway34129128922160Kishi T, Matsunaga S, Oya K, Nomura I, Ikuta T, Iwata N: Memantine for Alzheimer's Disease: An Updated Systematic Review and Meta-analysis. J Alzheimers Dis. 2017;60(2):401-425. doi: 10.3233/JAD-170424.118661Pathway34129226310825Lee SH, Kim SH, Noh YH, Choi BM, Noh GJ, Park WD, Kim EJ, Cho IH, Bae CS: Pharmacokinetics of Memantine after a Single and Multiple Dose of Oral and Patch Administration in Rats. Basic Clin Pharmacol Toxicol. 2016 Feb;118(2):122-7. doi: 10.1111/bcpt.12479. Epub 2015 Sep 28.118661Pathway34129329126136Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.118661Pathway1CellCL:00000005HepatocyteCL:00001824CardiomyocyteCL:00007463NeuronCL:00005407Epithelial CellCL:00000666MyocyteCL:000018712AstrocyteCL:00001272Platelet CL:00002338Beta cellCL:000063932Acinar CellCL:000062223T CellCL:000008426Endothelial cellCL:00001151Homo sapiens9606EukaryoteHuman3Escherichia coli562Prokaryote24Solanum lycopersicum4081EukaryoteTomato4Arabidopsis thaliana3702EukaryoteThale cress18Saccharomyces cerevisiae4932EukaryoteYeast49Bathymodiolus platifrons220390EukaryoteDeep sea mussel23Pseudomonas aeruginosa287Prokaryote12Mus musculus10090EukaryoteMouse17Rattus norvegicus10116EukaryoteRat5Bos taurus9913EukaryoteCattle10Drosophila melanogaster7227EukaryoteFruit fly6Caenorhabditis elegans6239EukaryoteRoundworm2Bacteria2ProkaryoteBacteria19Schizosaccharomyces pombe4896Eukaryote21Xenopus laevis8355EukaryoteAfrican clawed frog25Escherichia coli (strain K12)83333Prokaryote60Nitzschia sp.0001EukaryoteNitzschia4157Acinetobacter baumannii 107673Prokaryote5CytoplasmGO:00057373Mitochondrial MatrixGO:00057591CytosolGO:000582911Extracellular SpaceGO:000561531Periplasmic SpaceGO:00056202MitochondrionGO:000573935ChloroplastGO:000950732Inner MembraneGO:00702586LysosomeGO:00057644PeroxisomeGO:000577710Cell MembraneGO:000588616Lysosomal LumenGO:00432027Endoplasmic Reticulum MembraneGO:000578918Melanosome MembraneGO:003316213Endoplasmic ReticulumGO:000578325Golgi ApparatusGO:000579414Mitochondrial Outer MembraneGO:000574112Mitochondrial Inner MembraneGO:000574320Endoplasmic Reticulum LumenGO:000578821SynapseGO:004520215NucleusGO:000563436MembraneGO:001602053Endoplasmic Reticulum BodyGO:001016834Plant-Type VacuoleGO:000032540PeriplasmGO:004259724Mitochondrial Intermembrane SpaceGO:000575819Sarcoplasmic ReticulumGO:001652922post-synaptic membraneGO:004521154Endocytic VesicleGO:003013955Exocytic VesicleGO:007038267Exocytic Vesicle membraneGO:001250665Presynaptic membraneGO:00427341LiverBTO:00007597294Adrenal MedullaBTO:000004971825IntestineBTO:000064828StomachBTO:0001307155267Nervous SystemBTO:00014848Blood VesselBTO:0001102741111HeartBTO:000056273106KidneyBTO:00006717189MuscleBTO:00008871411824BrainBTO:000014289162Endothelium BTO:00003935cardiocyteBTO:000153918PancreasBTO:000098847Spinal cordBTO:000127926LungBTO:00007633Sympathetic Nervous SystemBTO:000183214EyeBTO:00004391532422BladderBTO:000012348Salivary 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(Gln) is one of the 20 amino acids encoded by the standard genetic code. Its side chain is an amide; it is formed by replacing a side-chain hydroxyl of glutamic acid with an amine functional group. glutamine is found in foods high in proteins, such as fish, red meat, beans, and dairy products. glutamine is a supplement that is used in weightlifting, bodybuilding, endurance and other sports, as well as by those who suffer from muscular cramps or pain particularly elderly people. The main use of glutamine within the diet of either group is as a means of replenishing the body's stores of amino acids that have been used during exercise or everyday activities. Studies which are looking into problems with excessive consumption of glutamine thus far have proved inconclusive. However, normal supplementation is healthy mainly because glutamine is supposed to be supplemented after prolonged periods of exercise (for example, a workout or exercise in which amino acids are required for use) and replenishes amino acid stores; this being the main reason glutamine is recommended during fasting or for people who suffer from physical trauma, immune deficiencies, or cancer. There is a significant body of evidence that links glutamine-enriched diets with intestinal effects; aiding maintenance of gut barrier function, intestinal cell proliferation and differentiation, as well as generally reducing septic morbidity and the symptoms of Irritable Bowel Syndrome. The reason for such "cleansing" properties is thought to stem from the fact that the intestinal extraction rate of glutamine is higher than that for other amino acids, and is therefore thought to be the most viable option when attempting to alleviate conditions relating to the gastrointestinal tract. These conditions were discovered after comparing plasma concentration within the gut between glutamine-enriched and non glutamine-enriched diets. However, even though glutamine is thought to have "cleansing" properties and effects, it is unknown to what extent glutamine has clinical benefits, due to the varied concentrations of glutamine in varieties of food. It is also known that glutamine has various effects in reducing healing time after operations. Hospital waiting times after abdominal surgery are reduced by providing parenteral nutrition regimens containing amounts of glutamine to patients. Clinical trials have revealed that patients on supplementation regimes containing glutamine have improved nitrogen balances, generation of cysteinyl-leukotrienes from polymorphonuclear neutrophil granulocytes and improved lymphocyte recovery and intestinal permeability (in postoperative patients) - in comparison to those who had no glutamine within their dietary regime; all without any side-effects. (http://en.wikipedia.org/wiki/glutamine).56-85-9C00064596118050GLN5746DB00130N[C@@H](CCC(N)=O)C(O)=OC5H10N2O3InChI=1S/C5H10N2O3/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H2,7,8)(H,9,10)/t3-/m0/s1ZDXPYRJPNDTMRX-VKHMYHEASA-N(2S)-2-amino-4-carbamoylbutanoic acid146.1445146.069142196-0.173L-glutamine00FDB012164(2s)-2,5-diamino-5-oxopentanoate;(2s)-2,5-diamino-5-oxopentanoic acid;(2s)-2-amino-4-carbamoylbutanoate;(2s)-2-amino-4-carbamoylbutanoic acid;(s)-2,5-diamino-5-oxopentanoate;(s)-2,5-diamino-5-oxopentanoic acid;2-aminoglutaramic acid;Cebrogen;Glavamin;Glumin;Glutamic acid 5-amide;Glutamic acid amide;Glutamine;L-(+)-glutamine;L-2-aminoglutaramic acid;L-2-aminoglutaramidic acid;L-glutamic acid 5-amide;L-glutamic acid gamma-amide;L-glutamid;L-glutamide;L-glutamin;L-glutamine;L-glutaminsaeure-5-amid;Levoglutamid;Levoglutamida;Levoglutamide;Levoglutamidum;Levoglutamina;Polyglutamine;Stimulina;Gamma-glutamine;Q;Glutamate 5-amide;Glutamate amidePW_C000500Gln61844342701230211556581075659108606815768461666847383902251179319812692290423523184235331577016253772961117733313378395132791641147926411680652135113207941162071091200381221203484061212194091219611241229981201237891371245141181254162971256684791263592991268124831269562051271635011277183881284112081420WaterHMDB0002111Water is a chemical substance that is essential to all known forms of life. It appears colorless to the naked eye in small quantities, though it is actually slightly blue in color. It covers 71% of Earth's surface. Current estimates suggest that there are 1.4 billion cubic kilometers (330 million m3) of it available on Earth, and it exists in many forms. It appears mostly in the oceans (saltwater) and polar ice caps, but it is also present as clouds, rain water, rivers, freshwater aquifers, lakes, and sea ice. Water in these bodies perpetually moves through a cycle of evaporation, precipitation, and runoff to the sea. Clean water is essential to human life. In many parts of the world, it is in short supply. From a biological standpoint, water has many distinct properties that are critical for the proliferation of life that set it apart from other substances. It carries out this role by allowing organic compounds to react in ways that ultimately allow replication. All known forms of life depend on water. Water is vital both as a solvent in which many of the body's solutes dissolve and as an essential part of many metabolic processes within the body. Metabolism is the sum total of anabolism and catabolism. In anabolism, water is removed from molecules (through energy requiring enzymatic chemical reactions) in order to grow larger molecules (e.g. starches, triglycerides and proteins for storage of fuels and information). In catabolism, water is used to break bonds in order to generate smaller molecules (e.g. glucose, fatty acids and amino acids to be used for fuels for energy use or other purposes). Water is thus essential and central to these metabolic processes. Water is also central to photosynthesis and respiration. Photosynthetic cells use the sun's energy to split off water's hydrogen from oxygen. Hydrogen is combined with CO2 (absorbed from air or water) to form glucose and release oxygen. All living cells use such fuels and oxidize the hydrogen and carbon to capture the sun's energy and reform water and CO2 in the process (cellular respiration). Water is also central to acid-base neutrality and enzyme function. An acid, a hydrogen ion (H+, that is, a proton) donor, can be neutralized by a base, a proton acceptor such as hydroxide ion (OH-) to form water. Water is considered to be neutral, with a pH (the negative log of the hydrogen ion concentration) of 7. Acids have pH values less than 7 while bases have values greater than 7. Stomach acid (HCl) is useful to digestion. However, its corrosive effect on the esophagus during reflux can temporarily be neutralized by ingestion of a base such as aluminum hydroxide to produce the neutral molecules water and the salt aluminum chloride. Human biochemistry that involves enzymes usually performs optimally around a biologically neutral pH of 7.4. (Wikipedia).7732-18-5C0000196215377937OH2OInChI=1S/H2O/h1H2XLYOFNOQVPJJNP-UHFFFAOYSA-Nwater18.015318.0105646861water00FDB013390Dihydrogen oxide;Steam;[oh2];Acqua;Agua;Aqua;Bound water;Dihydridooxygen;Eau;H2o;Hoh;Hydrogen hydroxide;WasserPW_C001420H2O558949109513941513162144811352615624286521069120770338231883821094311377491465541590432018242532222678602727462778172805293143703164723634614598364727374941935030275156751959752141005227945236103529710553191115343113535511254021105470123548312554921265507127553413055371145541129559113556081185622108569165759140577810158411435853146587710758909559101475940151603215560591576087161612316361331596215162181666477178650718066001526713117684018868881607162205718120771932067211211722821372382147243215729519873502167388210740121274672227492224750019075881708201225823722684141629265261185027711922164120112811221328512250286122642871232724912520227126326512693290127052911271529213007298130193001302530113037302132612231332729415340308423273154269531843691322769142937701925377102132771311337721513477378331773973327747133377516115775363347762833677722337777593417781634377982347780713297823535278242353782703567911336080014368800393708059122880656119938303839479438411055739011063939111584439811987923211991512211996340612000840712004640812011312412036541212043040512043840912060641512079441412115842512124042912135112112138141912160743412211838212238443612275312012279737412280444312301244612306437612307213712313144712314213612316244812323145112338445012373046012381046412394045512416546912467039912493847112494547212530529712535347912538648112542448212548029912568248312570747812574548712605449012623849512627348412676448012689650112696350212701738812717720812719920912722750412750650712757651512783638912808239512817651314067479014067583414075518595L-Glutamic acidHMDB0000148Glutamic 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 Alzheimer's 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).56-86-0C000253303216015GLT30572DB00142N[C@@H](CCC(O)=O)C(O)=OC5H9NO4InChI=1S/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)/t3-/m0/s1WHUUTDBJXJRKMK-VKHMYHEASA-N(2S)-2-aminopentanedioic acid147.1293147.053157781-0.263L-glutamic acid0-1FDB012535(2s)-2-aminopentanedioate;(2s)-2-aminopentanedioic acid;(s)-(+)-glutamate;(s)-(+)-glutamic acid;(s)-2-aminopentanedioate;(s)-2-aminopentanedioic acid;(s)-glutamate;(s)-glutamic acid;1-amino-propane-1,3-dicarboxylate;1-amino-propane-1,3-dicarboxylic acid;1-aminopropane-1,3-dicarboxylate;1-aminopropane-1,3-dicarboxylic acid;2-aminoglutarate;2-aminoglutaric acid;2-aminopentanedioate;2-aminopentanedioic acid;Aciglut;Aminoglutarate;Aminoglutaric acid;E;Glt;Glu;Glusate;Glut;Glutacid;Glutamicol;Glutamidex;Glutaminate;Glutaminic acid;Glutaminol;Glutaton;L-(+)-glutamate;L-(+)-glutamic acid;L-glu;L-glutamate;L-glutaminate;L-glutaminic acid;L-a-aminoglutarate;L-a-aminoglutaric acid;L-alpha-aminoglutarate;L-alpha-aminoglutaric acid;A-aminoglutarate;A-aminoglutaric acid;A-glutamate;A-glutamic acid;Alpha-aminoglutarate;Alpha-aminoglutaric acid;Alpha-glutamate;Alpha-glutamic acid;Acide glutamique;Acido glutamico;Acidum glutamicum;Glutamate;Glutamic acid;L-glutaminsaeurePW_C000095Glu162443658119113841641496991105421448501456261462545323111534411354151175439118556513256311075632108585910560061476071157619194653185683818768441887092727093717165205718220775142247518151820822583732201179219811855161120042221262131126832891269729042348315423493184284532077020253773321337752511277971346779773277798134778291345806491351200231241200401221200864071203474061206921261208164181211474231211534241211574251228331191229971201232994431234014541237194581237254591237294601254012991254182971254574811256674791257693011258024891269413881269952061271625011272575061407388414073959735AmmoniaHMDB0000051Ammonia is a colourless alkaline gas and is one of the most abundant nitrogen-containing compounds in the atmosphere. It is an irritant with a characteristic pungent odor that is widely used in industry. Inasmuch as ammonia is highly soluble in water and, upon inhalation, is deposited in the upper airways, occupational exposures to ammonia have commonly been associated with sinusitis, upper airway irritation, and eye irritation. Acute exposures to high levels of ammonia have also been associated with diseases of the lower airways and interstitial lung. Small amounts of ammonia are naturally formed in nearly all tissues and organs of the vertebrate organism. Ammonia is both a neurotoxin and a metabotoxin. In fact, it is the most common endogenous neurotoxin. A neurotoxin is a compound that causes damage to neural tissue and neural cells. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Ammonia is recognized to be central in the pathogenesis of a brain condition known as hepatic encephalopathy, which arises from various liver diseases and leads to a build up ammonia in the blood (hyperammonemia). More than 40% of people with cirrhosis develop hepatic encephalopathy. Part of the neurotoxicity of ammonia arises from the fact that it easily crosses the blood-brain barrier and is absorbed and metabolized by the astrocytes, a population of cells in the brain that constitutes 30% of the cerebral cortex. Astrocytes use ammonia when synthesizing glutamine from glutamate. The increased levels of glutamine lead to an increase in osmotic pressure in the astrocytes, which become swollen. There is increased activity of the inhibitory gamma-aminobutyric acid (GABA) system, and the energy supply to other brain cells is decreased. This can be thought of as an example of brain edema. The source of the ammonia leading to hepatic encephalopathy is not entirely clear. The gut produces ammonia, which is metabolized in the liver, and almost all organ systems are involved in ammonia metabolism. Colonic bacteria produce ammonia by splitting urea and other amino acids, however this does not fully explain hyperammonemia and hepatic encephalopathy. The alternative explanation is that hyperammonemia is the result of the intestinal breakdown of amino acids, especially glutamine. The intestines have significant glutaminase activity, predominantly located in the enterocytes. On the other hand, intestinal tissues only have a little glutamine synthetase activity, making it a major glutamine-consuming organ. In addition to the intestine, the kidney is an important source of blood ammonia in patients with liver disease. Ammonia is also taken up by the muscle and brain in hepatic coma, and there is confirmation that ammonia is metabolized in muscle. Excessive formation of ammonia in the brains of Alzheimer's disease patients has also been demonstrated, and it has been shown that some Alzheimer's disease patients exhibit elevated blood ammonia concentrations. Ammonia is the most important natural modulator of lysosomal protein processing. Indeed, there is strong evidence for the involvement of aberrant lysosomal processing of beta-amyloid precursor protein (beta-APP) in the formation of amyloid deposits. Inflammatory processes and activation of microglia are widely believed to be implicated in the pathology of Alzheimer's disease. Ammonia is able to affect the characteristic functions of microglia, such as endocytosis, and cytokine production. Based on these facts, an ammonia-based hypothesis for Alzheimer's disease has been suggested (PMID: 17006913, 16167195, 15377862, 15369278). Chronically high levels of ammonia in the blood are associated with nearly twenty different inborn errors of metabolism including: 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, 3-methyl-crotonylglycinuria, argininemia, argininosuccinic aciduria, beta-ketothiolase deficiency, biotinidase deficiency, carbamoyl phosphate synthetase deficiency, carnitine-acylcarnitine translocase deficiency, citrullinemia type I, hyperinsulinism-hyperammonemia syndrome, hyperornithinemia-hyperammonemia-homocitrullinuria syndrome, isovaleric aciduria, lysinuric protein intolerance, malonic aciduria, methylmalonic aciduria, methylmalonic aciduria due to cobalamin-related disorders, propionic acidemia, pyruvate carboxylase deficiency, and short chain acyl CoA dehydrogenase deficiency (SCAD deficiency). Many of these inborn errors of metabolism are associated with urea cycle disorders or impairment of amino acid metabolism. High levels of ammonia in the blood (hyperammonemia) lead to the activation of NMDA receptors in the brain. This results in the depletion of brain ATP, which in turn leads to the release of glutamate. Ammonia also leads to the impairment of mitochondrial function and calcium homeostasis, thereby decreasing ATP synthesis. Excess ammonia also increases the formation of nitric oxide (NO), which in turn reduces the activity of glutamine synthetase, and thereby decreases the elimination of ammonia in the brain (PMID: 12020609). As a neurotoxin, ammonia predominantly affects astrocytes. Disturbed mitochondrial function and oxidative stress, factors implicated in the induction of the mitochondrial permeability transition, appear to be involved in the mechanism of ammonia neurotoxicity. Ammonia can also affect the glutamatergic and GABAergic neuronal systems, the two prevailing neuronal systems of the cortical structures. All of these effects can lead to irreversible brain damage, coma, and/or death. Infants with urea cycle disorders and hyperammonemia initially exhibit vomiting and increasing lethargy. If untreated, seizures, hypotonia (poor muscle tone, floppiness), respiratory distress (respiratory alkalosis), and coma can occur. Adults with urea cycle disorders and hyperammonemia will exhibit episodes of disorientation, confusion, slurred speech, unusual and extreme combativeness or agitation, stroke-like symptoms, lethargy, and delirium. Ammonia also has toxic effects when an individual is exposed to ammonia solutions. Acute exposure to high levels of ammonia in air may be irritating to skin, eyes, throat, and lungs and cause coughing and burns. Lung damage and death may occur after exposure to very high concentrations of ammonia. Swallowing concentrated solutions of ammonia can cause burns in the mouth, throat, and stomach. Splashing ammonia into eyes can cause burns and even blindness.7664-41-7C0001422216134AMMONIA217NH3NInChI=1S/H3N/h1H3QGZKDVFQNNGYKY-UHFFFAOYSA-Nammonia17.030517.0265491011ammonia01FDB003908Ammonia anhydrous;Ammonia inhalant;Ammonia solution strong [usan];Ammonia water;Ammoniak;Liquid ammonia;Am-fol;Ammonia;Ammonia (conc 20% or greater);Ammonia gas;Ammonia solution;Ammonia solution strong (nf);Ammonia water (jp15);Ammoniac [french];Ammoniaca [italian];Ammoniacum gummi;Ammoniak [german];Ammoniak kconzentrierter;Ammoniakgas;Ammonium ion;Amoniak [polish];Anhydrous ammonia;Aromatic ammonia vaporole;Azane;Nh(3);Nh3;Nitro-sil;Primaeres amin;Sekundaeres amin;Spirit of hartshorn;Tertiaeres amin;[nh3];Ammoniac;Amoniaco;R-717;Ammonia solution strongPW_C000035NH39791125133814244382479135501414685425332225723533811160161477022160717720511786198118482771188521512708291127182927696622577046294773291337734313277469333774991137753933477597115779853477799311278072329792442938065013580657119116203109119921122120049408120053126120136407120343406120363412120462405121046124121161425122119382122800374122805443122993120123010446123096376123610118123733460124671399125311297125427482125431301125502481125663479125708478126102299126274484126966502126970207127039206127158501127200209127600388127837389353CalciumHMDB0000464Calcium is essential for the normal growth and maintenance of bones and teeth, and calcium requirements must be met throughout life. Requirements are greatest during periods of growth, such as childhood, during pregnancy and when breast-feeding. Long-term calcium deficiency can lead to osteoporosis, in which the bone deteriorates and there is an increased risk of fractures. Adults need between 1,000 and 1,300 mg of calcium in their daily diet. Calcium is essential for living organisms, particularly in cell physiology, and is the most common metal in many animals. Physiologically, it exists as an ion in the body. Calcium combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Calcium is an important component of a healthy diet. A deficit can affect bone and tooth formation, while overretention can cause kidney stones. Vitamin D is needed to absorb calcium. Dairy products, such as milk and cheese, are a well-known source of calcium. However, some individuals are allergic to dairy products and even more people, particularly those of non-European descent, are lactose-intolerant, leaving them unable to consume dairy products. Fortunately, many other good sources of calcium exist. These include: seaweeds such as kelp, wakame and hijiki; nuts and seeds (like almonds and sesame); beans; amaranth; collard greens; okra; rutabaga; broccoli; kale; and fortified products such as orange juice and soy milk. Calcium has also been found to assist in the production of lymphatic fluids.14127-61-8C0007627129108CA%2b2266DB01373[Ca++]CaInChI=1S/Ca/q+2BHPQYMZQTOCNFJ-UHFFFAOYSA-Ncalcium(2+) ion40.07839.9625911550calcium(2+) ion22FDB003513Ca;Calcium element;Ca(2+);Ca2+;Calcium ion;Calcium, doubly charged positive ionPW_C000353Ca2+276163038553146012941159932199735104631163461164471478491491421552432116582138172796182937931597131607239422941866647821048222853401115780101717920572322117258160728119011774213118371981184221012198164122152851528815115350308693361773893317760011578154132782663567852634578724130789081148041374805892288182651120220122120465405121049124121300418121377419121850383121923125122370409122895135123099376123613118123870454123936455124403398124476136124924137125571297125711478125981489126009299126050490126533495127203209127434506127460388127502507128105390140676790140677834140695509474MemantineHMDB0015177Memantine is an amantadine derivative with low to moderate-affinity for NMDA receptors. It is a noncompetitive NMDA receptor antagonist that binds preferentially to NMDA receptor-operated cation channels. It blocks the effects of excessive levels of glutamate that may lead to neuronal dysfunction. It is under investigation for the treatment of Alzheimer's disease, but there has been no clinical support for the prevention or slowing of disease progression.19982-08-2C137364054643123914DB01043CC12CC3CC(C)(C1)CC(N)(C3)C2C12H21NInChI=1S/C12H21N/c1-10-3-9-4-11(2,6-10)8-12(13,5-9)7-10/h9H,3-8,13H2,1-2H3BUGYDGFZZOZRHP-UHFFFAOYSA-N3,5-dimethyladamantan-1-amine179.3018179.167399677-3.601memantine01Memantina [inn-spanish];Memantine [inn];Memantinum [inn-latin];1,3-dimethyl-5-adamantanamine;1-amino-3,5-dimethyladamantane;3,5-dimethyl-1-adamantanamine;3,5-dimethyl-1-aminoadamantane;3,5-dimethyltricyclo(3.3.1.1(3,7))decan-1-amine;Memantina;MemantinumPW_C009474Memanti23976Glutaminase kidney isoform, mitochondrialO94925
Catalyzes the first reaction in the primary pathway for the renal catabolism of glutamine. Plays a role in maintaining acid-base homeostasis. Regulates the levels of the neurotransmitter glutamate, the main excitatory neurotransmitter in the brain (PubMed:30575854, PubMed:30239721, PubMed:30970188).
GLS13.5.1.21427431044142803789143076601439102614391213145691391520Glutamate [NMDA] receptor subunit epsilon-1Q12879NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Activation requires binding of agonist to both types of subunitsHMDBP01642GRIN2A16p13.2U09002132777313215814140060787141872965142019228145694381515Glutamate [NMDA] receptor subunit zeta-1Q05586NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. Is involved in the cell surface targeting of NMDA receptorsHMDBP01635GRIN19q34.3L05666132767313215914140061787141873965142018228145695381521Glutamate [NMDA] receptor subunit epsilon-3Q14957NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycineHMDBP01643GRIN2C17q25AC06887411321601414006278714046573141874965145696381522Glutamate [NMDA] receptor subunit epsilon-2Q13224NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycineHMDBP01644GRIN2B12p12U2886216590891321611414006378714046673141875965145697381523Glutamate [NMDA] receptor subunit epsilon-4O15399NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycineHMDBP01645GRIN2D19q13.1-qterAC00840311321621414006478714046773141876965145698383065Glutamate [NMDA] receptor subunit 3AQ8TCU5NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. May play a role in the development of dendritic spines. May play a role in PPP2CB-NMDAR mediated signaling mechanismHMDBP07845GRIN3A9q31.1AB075853132787313216314140065787141877965142020228145699381519Glutamate [NMDA] receptor subunit 3BO60391NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycineHMDBP01639GRIN3B19p13.3AC0045281132164141400667871404687314159381014159485141878965145700382382Vesicular glutamate transporter 3Q8NDX2Mediates the uptake of glutamate into synaptic vesicles at presynaptic nerve terminals of excitatory neural cells. May also mediate the transport of inorganic phosphate.
HMDBP03945SLC17A812q23.1CH4710541141035870141869866145618144814569211192712Voltage-dependent P/Q-type calcium channel subunit alpha-1AO00555Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents. P/Q-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by the funnel toxin (Ftx) and by the omega-agatoxin- IVA (omega-Aga-IVA). They are however insensitive to dihydropyridines (DHP), and omega-conotoxin-GVIA (omega-CTx-GVIA)HMDBP07491CACNA1A19p13AC0987811939399423885032281363727413952945139530511397057781399054814063271406447871409973081410007314134852141932671419692142866103314287010551428981058143428114414558813671455961449145602136114564310001456491453145693111815529Glutaminase 1PW_P0155292570123976142744104410783NMDA Receptor1PW_P0107831928315201928415151928515211928615221928715231928830651928915191321571414965Vesicular Glutamate Transporter1PW_P0149652498823821262Voltage-dependent P/Q-type calcium channel subunit alpha-1A1PW_P0002622812712218411falsePW_R218411Right8420795001Compoundfalse84208014201Compoundfalse842081951Compoundfalse842082351Compoundfalse207831155293.5.1.214050PW_T014050144743531Compound84789Right5019107832022-02-09T15:53:01-07:002022-02-09T15:53:01-07:0096514087PW_T014087Active14511951Compound789866Right5048149652022-02-25T11:47:16-07:002022-02-25T11:47:16-07:0086614046PW_T01404614470951Compound866950Right13624PW_T013624140313531Compound788789Right47252622021-05-04T19:45:41-06:002021-05-04T19:45:41-06:0078715395PW_T015394Diffusion1584494741Compound51950Right3357ActivationPW_I003357671395Compound1671410783ProteinComplex13971ActivationPW_I0039717941353Compound1794295Compound14558InhibitionPW_I00455891159474Compound1911610783ProteinComplex1319856850078981false269166110regular2001903198569142078949false499159710regular787831985709578981false904166110regular20019031985713578963false764159710regular787831985753538451false2032148710regular7878319857635378951false2785148710regular787831985839586681false1369166110regular20019031985849595081false1969166110regular200190319858735378851false132592010regular7878319858835378951false1325138310regular787831986399474950157false2025123110regular2001903205470947451158false45527010regular30028032054719474950158false112527010regular3002801243107239767892false59817218subunitregular150701243110152096576false236014318subunitregular150701243111151576true252014668subunitregular150701243112152176true251014668subunitregular150701243113152296576false236015518subunitregular150701243114152376true264014668subunitregular150701243115306596576false232514918subunitregular150701243116151976true277014668subunitregular150701243121238286676false116917218subunitregular1507012431232712103376false128910938subunitregular15070977187155291184967891236555124310797719010783118496123655812431101236559124311112365601243112123656112431131236562124311412365631243115123656412431169771941496511849612365691243121977196262118496123657112431234387455M469 1756 C508 1755 560 1757 598 1756 5false184387456M538 1675 C537 1723 556 1754 598 1756 5false184387457M904 1756 C860 1757 801 1755 748 1756 5false18trueM 3130.9468550441647 13.26155629629604 L 3116 12 L 3122.380887721186 25.575134323078345false4387458M803 1675 C802 1729 795 1753 748 1756 5false18trueM 3130.9468550441647 13.26155629629604 L 3116 12 L 3122.380887721186 25.575134323078345false4387465M2110 1526 C2187 1525 2250 1524 2325 1526 83false184387466M2785 1526 C2668 1525 2530 1526 2475 1526 83false18trueM 1438.9468550441647 2504.261556296296 L 1424 2503 L 1430.380887721186 2516.575134323078false4387475M1104 1756 C1134 1756 1139 1756 1169 1756 83false184387476M1369 1756 C1339 1756 1349 1756 1319 1756 83false18trueM 25.946855044164835 3985.261556296296 L 11 3984 L 17.380887721185843 3997.575134323078false4387477M1569 1756 C1599 1756 1444 651 1474 651 83true184387478M1969 1756 C1939 1756 1599 1756 1569 1756 83false18trueM 249.94685504416483 3622.261556296296 L 235 3621 L 241.38088772118584 3634.575134323078false4387481M1364 998 C1364 1028 1364 1063 1364 1093 83false184387482M1364 1383 C1364 1353 1364 1193 1364 1163 83false18trueM 795.9468550441649 4560.2615562962965 L 781 4559 L 787.3808877211858 4572.575134323079false4387497M2169 1756 C2210 1759 2400 1591 2400 1561 149true184387498M2435 1621 C2436 1732 2245 1757 2169 1756 149false16trueM 1179.9468550441647 3977.261556296296 L 1165 3976 L 1171.380887721186 3989.575134323078false4387501M1403 1422 C1403 1452 1469 1631 1469 1661 149true184387502M1640 1748 C1640 1718 1642 1450 1642 1420 C1554 1421 1483 1420 1403 1422 149false18trueM 241.94685504416483 4272.2615562962965 L 227 4271 L 233.38088772118584 4284.575134323079false4387508M2863 1526 C2893 1526 3123 1526 3153 1526 5false18trueM 2248.0644009829866 3822.611518094107 L 2263 3824 L 2256.734661094692 3810.3711508775823false4387510M369 1661 C369 1631 371 1576 371 1546 5false18trueM 25.946855044164835 4669.2615562962965 L 11 4668 L 17.380887721185843 4681.575134323079false4387665M2125 1421 C2125 1451 2400 1461 2400 1491 148true184387666M2400 1491 C2400 1461 2355 1328 2225 1326 148false18falsetrueM 993.565967322979 2567.686421973218 L 985 2580 L 976.434032677021 2592.3135780267824403364M755 410 C785 410 1095 410 1125 410 83true184403365M1125 410 C1095 410 785 410 755 410 83false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false937415118496218411789380430931985684387455Left380431031985694387456Left380431131985704387457Right380431231985714387458Right8899322078319771871075401405011849621589431985754387465Left21589531985764387466Right5198997719050191075451408711849621590431985704387475Left21590531985834387476Right5199397719450481075461404611849621590631985834387477Left21590731985844387478Right1075481362411849621591031985874387481Left21591131985884387482Right5199597719647251091611539511849621896632054704403364Left21896732054714403365Right159663357118496965563731985844387497Left205049771904387498Right159683971118496866564031985884387501Left564131985834387502Right159904558118496950564431986394387665Left205459771904387666Right12039912017111849614false3153149114regular11792531985764387508Left12040112017311849614false296147616regular11792731985684387510Right488832262213791.01.00252400274488833233014921.31.301747102101488836226617120.60.601747102101488837317414811.01.0017471021014888389691251.71.7021650040048883918646191.11.1-9021334273148884025856221.11.1-902133427314929181053601.31.302217256109494084695350.80.865299861647477731M206 1374 C306 1374 839 1370 939 1370 C1039 1370 1039 1118 1339 1118 C1639 1118 1789 1381 1794 1681 C1789 1981 1641 2230 1341 2230 C1041 2230 1042 2023 942 2023 C842 2023 304 2018 204 2018 1false61590.01112.0477732M3401 1173 C3301 1173 3009 1174 2909 1174 C2809 1174 2533 933 2338 1033 C2233 1083 2404 1116 2404 1616 C2404 2116 2280 2160 2380 2210 C2580 2310 2781 1877 2886 1877 C2981 1877 3303 1883 3398 1883 1false61063.01177.0477737M1243 1692 C1243 1642 1293 1592 1343 1592 C1402 1592 1480 1592 1539 1592 C1589 1592 1639 1642 1639 1692 C1639 1733 1639 1785 1639 1826 C1639 1876 1589 1926 1539 1926 C1480 1926 1402 1926 1343 1926 C1293 1926 1243 1876 1243 1826 C1243 1785 1243 1733 1243 1692 238true6396.0334.0479157M929 123 C929 237 930 741 928 824 1false61.0701.0897650235Cytosol24421163201.91.92001589765515Mematine binds to the Glutamate NMDA receptor which prevents Glutamate from binding and activating the receptor. This prevents depolarization1777917202.82.816015897656235Postsynaptic Neuron29331091201.91.92001589765715Blocking the Glutamate NMDA receptor prevents depolarization of the neuron that is caused by an influx of calcium.29641181202.52.516015897658235Presynaptic Neuron3441288201.91.920015897660235Cytosol8491415201.91.92001589766215Glutamate can be synthesized in the neuron or often is synthesized in adjacent glial cells4691756202.52.51601589766815Glutamate would bind to the subunit epsilon-2 receptor, however since Mematine bound to the glutamate receptor, glutamate is unable to bind in order to open the calcium channel so calcium is unable to enter the neuron18631823202.52.516015897670235Synaptic Vesicle12731528201.61.620015897672235Synapse1705832202.22.220015902155235Blood-Brain Barrier76085201.61.620015902156235Diffusion800355201.31.32001528365626024332038793399225444319613752836571489410186324334016153941538372