64631PathwayNitric Oxide Signaling PathwayNitric oxide (NO) is a neurotransmitter that synthesized from L-arginine with faciltation of nitric oxide synthase (NOS). Nitric oxide is essential and required in central nervous system (CNS) and peripheral nervous system (PNS). Nitric oxide has several important functions such as immune responses, blood flow regulation and modulation of neurotransmission. Nitric oxide also participates in controlling sleep, adjusting body temperature, neurosecretion as well as synaptic modulation and plasticity in CNS. While in PNS, nitric oxide participates in visceral smooth muscle relaxation as well as vasodilation mediation.ProteinPW064769CenterPathwayVisualizationContext6504530003000#000099PathwayVisualization6451564631Nitric Oxide Signaling PathwayNitric oxide (NO) is a neurotransmitter that synthesized from L-arginine with faciltation of nitric oxide synthase (NOS). Nitric oxide is essential and required in central nervous system (CNS) and peripheral nervous system (PNS). Nitric oxide has several important functions such as immune responses, blood flow regulation and modulation of neurotransmission. Nitric oxide also participates in controlling sleep, adjusting body temperature, neurosecretion as well as synaptic modulation and plasticity in CNS. While in PNS, nitric oxide participates in visceral smooth muscle relaxation as well as vasodilation mediation.Protein122990826597676Zhang B, Bailey WM, Kopper TJ, Orr MB, Feola DJ, Gensel JC: Azithromycin drives alternative macrophage activation and improves recovery and tissue sparing in contusion spinal cord injury. J Neuroinflammation. 2015 Nov 24;12:218. doi: 10.1186/s12974-015-0440-3.64631Pathway2299091381738Katusic ZS: Role of nitric oxide signal transduction pathway in regulation of vascular tone. Int Angiol. 1992 Jan-Mar;11(1):14-9.64631Pathway229925https://cgap.nci.nih.gov/Pathways/BioCarta/h_nos1Pathway64631Pathway27952119273051Bryan NS, Bian K, Murad F: Discovery of the nitric oxide signaling pathway and targets for drug development. Front Biosci (Landmark Ed). 2009 Jan 1;14:1-18.64631Pathway27952210713088Godber BL, Doel JJ, Sapkota GP, Blake DR, Stevens CR, Eisenthal R, Harrison R: Reduction of nitrite to nitric oxide catalyzed by xanthine oxidoreductase. J Biol Chem. 2000 Mar 17;275(11):7757-63.64631Pathway2Platelet CL:00002331CellCL:00000004Cardiomyocyte CL:00007463NeuronCL:00005408Beta cellCL:00006395HepatocyteCL:00001827Epithelial CellCL:00000666MyocyteCL:00001871Homo sapiens9606EukaryoteHuman12Mus musculus10090EukaryoteMouse3Escherichia coli562Prokaryote6Caenorhabditis elegans6239EukaryoteRoundworm18Saccharomyces cerevisiae4932EukaryoteYeast4Arabidopsis thaliana3702EukaryoteThale cress5Bos taurus9913EukaryoteCattle17Rattus norvegicus10116EukaryoteRat10Drosophila melanogaster7227EukaryoteFruit fly2Bacteria2ProkaryoteBacteria19Schizosaccharomyces pombe4896Eukaryote24Solanum lycopersicum4081EukaryoteTomato21Xenopus laevis8355EukaryoteAfrican clawed frog49Bathymodiolus platifrons220390EukaryoteDeep sea mussel23Pseudomonas aeruginosa287Prokaryote60Nitzschia sp.0001EukaryoteNitzschia429Saccharomyces cerevisiae (strain ATCC 204508 / S288c)559292EukaryoteBaker's yeast25Escherichia coli (strain K12)83333Prokaryote62Acinetobacter baylyi (strain ATCC 33305 / BD413 / ADP1)62977Prokaryote5CytoplasmGO:000573710Cell MembraneGO:00058861CytosolGO:000582911Extracellular SpaceGO:000561519sarcoplasmic reticulumGO:00165292MitochondrionGO:00057397Endoplasmic Reticulum MembraneGO:000578924Mitochondrial Intermembrane SpaceGO:000575825Golgi apparatusGO:000579414Mitochondrial Outer MembraneGO:000574112Mitochondrial Inner MembraneGO:000574313Endoplasmic ReticulumGO:00057836LysosomeGO:000576416Lysosomal LumenGO:004320236MembraneGO:00160204PeroxisomeGO:000577720Endoplasmic Reticulum LumenGO:00057888Smooth Endoplasmic Reticulum GO:00057903Mitochondrial MatrixGO:000575931Periplasmic SpaceGO:000562035ChloroplastGO:000950734Plant-Type VacuoleGO:000032539Mitochondrial membraneGO:003196615NucleusGO:000563432Inner MembraneGO:00702582Endothelium BTO:00003935cardiocyteBTO:00015391LiverBTO:000075972918PancreasBTO:00009888Blood VesselBTO:0001102741125IntestineBTO:00006489MuscleBTO:00008871411816212PW_BS0000168511PW_BS00000814101PW_BS0000142111PW_BS00000215111PW_BS000015215114PW_BS0000213551914PW_BS0000353211PW_BS00000346114PW_BS000046471914PW_BS00004749711PW_BS000049422411PW_BS000042432511PW_BS0000435811411PW_BS000058171211PW_BS000017181311PW_BS0000189611PW_BS000009711113PW_BS00007172513PW_BS00007229111PW_BS0000296618518PW_BS000066101711PW_BS0000102811611PW_BS0000281115121PW_BS000111101531PW_BS000101205561PW_BS0000242111018PW_BS0000241601181PW_BS0001601901118PW_BS0000242137181PW_BS0000241985181PW_BS00002421013181PW_BS0000241644PW_BS0001642851041PW_BS000024151141PW_BS0001513081011PW_BS00002411PW_BS0000013317121PW_BS0000281151012PW_BS0001151321121PW_BS00013235625121PW_BS00002834524121PW_BS00002813013121PW_BS0001301141112PW_BS0001147413PW_BS000074228361PW_BS0000245181PW_BS000051122551PW_BS000122405105PW_BS000115124151PW_BS0001244182451PW_BS0001154192551PW_BS000115383751PW_BS0001001251351PW_BS000125409115PW_BS0001151355171PW_BS0001353761017PW_BS0000531181171PW_BS00011845424171PW_BS00011545525171PW_BS0001153987171PW_BS00011313613171PW_BS0001361371117PW_BS0001372975101PW_BS0000244781010PW_BS00011548924101PW_BS0001152991101PW_BS00002449025101PW_BS0001154957101PW_BS000115209106PW_BS0000245062461PW_BS000115388161PW_BS0001125072561PW_BS000115390761PW_BS0001125411PW_BS0000053612011PW_BS000036111811PW_BS000011261115PW_BS0000264311PW_BS000004311511PW_BS000031951721PW_BS0000951231751PW_BS00012312915121PW_BS00012914117191PW_BS00014178811PW_BS0000781613181PW_BS00016129817101PW_BS00002430013101PW_BS00002429341PW_BS0000242491341PW_BS00002433217121PW_BS0000283361121PW_BS0000283344121PW_BS0000281333121PW_BS0001331122121PW_BS00011213412121PW_BS000134408451PW_BS000115407251PW_BS000115429151PW_BS000115406351PW_BS0001153841251PW_BS00010044717171PW_BS0001153744171PW_BS0000531192171PW_BS0001194641171PW_BS0001151203171PW_BS00012012112171PW_BS0001214824101PW_BS0001154812101PW_BS0001154793101PW_BS00011548012101PW_BS000115502461PW_BS000115206261PW_BS0000243951361PW_BS000113501361PW_BS0001153911261PW_BS000112221411PW_BS00002213121PW_BS0000136131PW_BS000006103331PW_BS0001031021231PW_BS000102126651PW_BS00012612711651PW_BS0001271553241PW_BS00015515612241PW_BS00015616212181PW_BS0001621783211PW_BS00017817912211PW_BS000179107313PW_BS0001071632181PW_BS000163222341PW_BS0000242231241PW_BS000024224241PW_BS0000242164181PW_BS0000242156181PW_BS0000242253541PW_BS0000242273441PW_BS000024226441PW_BS0000242916491PW_BS0000242924491PW_BS0000243016101PW_BS000024302116101PW_BS0000243183123PW_BS0000241136121PW_BS000113337116121PW_BS00002832914121PW_BS0000283583912PW_BS0000283683601PW_BS00002836912601PW_BS0000283821451PW_BS0001004436171PW_BS000115448116171PW_BS00011539914171PW_BS00011348414101PW_BS000115207661PW_BS0000243891461PW_BS000112612517PW_BS000061231511PW_BS00002327151PW_BS000027711PW_BS000007971521PW_BS000097100521PW_BS00010010813PW_BS00010814315191PW_BS0001431465191PW_BS0001461471241PW_BS000147117131PW_BS000117188118PW_BS00002421217181PW_BS000024241529PW_BS00002425715291PW_BS00002417018PW_BS0001702811251PW_BS0000242905491PW_BS00002430412PW_BS000024315123PW_BS0000243221231PW_BS000024253541PW_BS00002435325127PW_BS000028943PW_BS000094109323PW_BS00010947225177PW_BS0001155131761PW_BS00011521815181PW_BS00002412815121PW_BS0001284101551PW_BS00011544415171PW_BS00011548515101PW_BS0001155161561PW_BS000115731013PW_BS000073509516PW_BS0000506531624PW_BS000508231391PW_BS00002465413621PW_BS000508353CalciumHMDB0000464Calcium 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+2761630385531460129411599321997351046311634611644714784914914215524321165821381727961829379315971316072394229418666478210482228534011157801017179205723221172581607281190117742131183719811842210121981641221528515288151153503086933617738933177600115781541327826635678526345787241307890811480413748058922881826511202201221204654051210491241213004181213774191218503831219231251223704091228951351230993761236131181238704541239364551244033981244761361249241371255712971257114781259814891260092991260504901265334951272032091274345061274603881275025071281053901799HemeHMDB0003178Heme is the color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic subunit; these are known as hemoproteins.14875-96-8C0003217627HEME_A24604415DB02577CC1=C(CCC(O)=O)C2=CC3=[N+]4C(=CC5=C(C)C(C=C)=C6C=C7C(C)=C(C=C)C8=[N+]7[Fe--]4(N2C1=C8)N56)C(C)=C3CCC(O)=OC34H32FeN4O4InChI=1S/C34H34N4O4.Fe/c1-7-21-17(3)25-13-26-19(5)23(9-11-33(39)40)31(37-26)16-32-24(10-12-34(41)42)20(6)28(38-32)15-30-22(8-2)18(4)27(36-30)14-29(21)35-25;/h7-8,13-16H,1-2,9-12H2,3-6H3,(H4,35,36,37,38,39,40,41,42);/q;+2/p-2/b25-13-,26-13-,27-14-,28-15-,29-14-,30-15-,31-16-,32-16-;KABFMIBPWCXCRK-RGGAHWMASA-L4,20-bis(2-carboxyethyl)-10,15-diethenyl-5,9,14,19-tetramethyl-2lambda5,22,23lambda5,25-tetraaza-1-ferraoctacyclo[11.9.1.1^{1,8}.1^{3,21}.0^{2,6}.0^{16,23}.0^{18,22}.0^{11,25}]pentacosa-2,4,6,8,10,12,14,16(23),17,19,21(24)-undecaene-2,23-bis(ylium)-1,1-diuide616.487616.177297665-5.4824,20-bis(2-carboxyethyl)-10,15-diethenyl-5,9,14,19-tetramethyl-2lambda5,22,23lambda5,25-tetraaza-1-ferraoctacyclo[11.9.1.1^{1,8}.1^{3,21}.0^{2,6}.0^{16,23}.0^{18,22}.0^{11,25}]pentacosa-2,4,6,8,10,12,14,16(23),17,19,21(24)-undecaene-2,23-bis(ylium)-1,1-diuide0-2FDB016272(protoporphyrinato)iron;Ferroheme;Ferroheme b;Ferroprotoheme;Ferroprotoporphyrin;Ferroprotoporphyrin ix;Ferrous protoheme;Ferrous protoheme ix;Haem;Hem;Heme;Iron protoporphyrin;Iron protoporphyrin ix;Iron(ii) protoporphyrin ix;Protoferroheme;Protohaem;Protoheme;Protoheme ix;Reduced hematinPW_C001799Heme247163081032486082766512443135449141336196318280629293893238113367263421143734440433148232851709554721235485125551712958301416246786283165971517044160706016173262131183519811898211120651641300929813021300422781776915293769312497735111177364130773673317739833277517115776293367781333478380133786021327896311279932134120431405120603408120955407121085383121658429121746124121910122122570406122691384123065376123133447123144136123228374123521119123650398124216464124297118124463135125142120125277121125742482125896481126196299126499297126512495126718479126827480127224502127357206127632388128070205128083395128086390128309501128434391964FADHMDB0001248FAD, also known as flavitan or adeflavin, belongs to the class of organic compounds known as flavin nucleotides. These are nucleotides containing a flavin moiety. Flavin is a compound that contains the tricyclic isoalloxazine ring system, which bears 2 oxo groups at the 2- and 4-positions. FAD is a drug which is used to treat eye diseases caused by vitamin b2 deficiency, such as keratitis and blepharitis. FAD is slightly soluble (in water) and a moderately acidic compound (based on its pKa). FAD has been found in human liver and muscle tissues, and has also been detected in multiple biofluids, such as feces and blood. Within the cell, FAD is primarily located in the cytoplasm, mitochondria, endoplasmic reticulum and peroxisome. FAD exists in all living organisms, ranging from bacteria to humans. In humans, FAD is involved in the risedronate action pathway, the ibandronate action pathway, the valine, leucine and isoleucine degradation pathway, and the pyrimidine metabolism pathway. FAD is also involved in several metabolic disorders, some of which include the oncogenic action OF L-2-hydroxyglutarate in hydroxygluaricaciduria pathway, gaba-transaminase deficiency, 4-hydroxybutyric aciduria/succinic semialdehyde dehydrogenase deficiency, and the saccharopinuria/hyperlysinemia II pathway. FAD is a condensation product of riboflavin and adenosine diphosphate. The coenzyme of various aerobic dehydrogenases, e.g., D-amino acid oxidase and L-amino acid oxidase. (Lehninger, Principles of Biochemistry, 1982, p972).146-14-5C0001664397516238FAD559059DB03147CC1=CC2=C(C=C1C)N(C[C@H](O)[C@H](O)[C@H](O)CO[P@](O)(=O)O[P@@](O)(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC3=C1N=CN=C3N)C1=NC(=O)NC(=O)C1=N2C27H33N9O15P2InChI=1S/C27H33N9O15P2/c1-10-3-12-13(4-11(10)2)35(24-18(32-12)25(42)34-27(43)33-24)5-14(37)19(39)15(38)6-48-52(44,45)51-53(46,47)49-7-16-20(40)21(41)26(50-16)36-9-31-17-22(28)29-8-30-23(17)36/h3-4,8-9,14-16,19-21,26,37-41H,5-7H2,1-2H3,(H,44,45)(H,46,47)(H2,28,29,30)(H,34,42,43)/t14-,15+,16+,19-,20+,21+,26+/m0/s1VWWQXMAJTJZDQX-UYBVJOGSSA-N{[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}[({[(2R,3S,4S)-5-{7,8-dimethyl-2,4-dioxo-2H,3H,4H,10H-benzo[g]pteridin-10-yl}-2,3,4-trihydroxypentyl]oxy}(hydroxy)phosphoryl)oxy]phosphinic acid785.5497785.157134455-2.279flavine-adenine dinucleotide0-3FDB0225111h-purin-6-amine flavin dinucleotide;1h-purin-6-amine flavine dinucleotide;Adenine-flavin dinucleotide;Adenine-flavine dinucleotide;Adenine-riboflavin dinuceotide;Adenine-riboflavin dinucleotide;Adenine-riboflavine dinucleotide;Fad;Flamitajin b;Flanin f;Flavin adenine dinucleotide;Flavin adenine dinucleotide oxidized;Flavin-adenine dinucleotide;Flavine adenosine diphosphate;Flavine-adenine dinucleotide;Flavitan;Flaziren;Isoalloxazine-adenine dinucleotide;Riboflavin 5'-adenosine diphosphate;Riboflavin-adenine dinucleotide;Riboflavine-adenine dinucleotide;AdeflavinPW_C000964FAD99911451868192321642531762828825188402118814148942161229162249213358253622372326460236468831474113475810488165268103528510253351115496126551112756131186030155605415660821616116162639016475178649917966661077039163717520573212137465222748722390762241181821611887215118992111229622512328249124431511251922712595226127102911272029213029301130413024362331877080293771261337715213477501113775071127751811577541334776151327772633778054329783753457893033179222336792723588001236880034369807141191199584061199993841200514081201074071204324051204531221204901241212784291212984181214173821214893831227481201227761211228023741228234431230663761230871351231664481238494641238684541239763991240473981253484791253784801254294821254744811256972971259794891261072991262774841268915011269203911269685021269872071270112061273102091274325061276023881278403891170Flavin MononucleotideHMDB0001520Flavin mononucleotide (FMN), or riboflavin-5?-phosphate, is a biomolecule produced from riboflavin (vitamin B2) by the enzyme riboflavin kinase and functions as prosthetic group of various oxidoreductases including NADH dehydrogenase as well as cofactor in biological blue-light photo receptors. During the catalytic cycle, the reversible interconversion of oxidized (FMN), semiquinone (FMNH) and reduced (FMNH2) forms occurs in the various oxidoreductases. FMN is a stronger oxidizing agent than NAD and is particularly useful because it can take part in both one- and two-electron transfers. Flavin mononucleotide is also used as an orange-red food colour additive. It is the principal form in which riboflavin is found in cells and tissues.146-17-8C0006164397617621FMN559060DB03247CC1=CC2=C(C=C1C)N(C[C@H](O)[C@H](O)[C@H](O)COP(O)(O)=O)C1=NC(=O)NC(=O)C1=N2C17H21N4O9PInChI=1S/C17H21N4O9P/c1-7-3-9-10(4-8(7)2)21(15-13(18-9)16(25)20-17(26)19-15)5-11(22)14(24)12(23)6-30-31(27,28)29/h3-4,11-12,14,22-24H,5-6H2,1-2H3,(H,20,25,26)(H2,27,28,29)/t11-,12+,14-/m0/s1FVTCRASFADXXNN-SCRDCRAPSA-N{[(2R,3S,4S)-5-{7,8-dimethyl-2,4-dioxo-2H,3H,4H,10H-benzo[g]pteridin-10-yl}-2,3,4-trihydroxypentyl]oxy}phosphonic acid456.3438456.104614802-2.836riboflavin 5'-phosphate0-3FDB001984Fmn;Flanin;Flavine mononucleotide;Flavol;Riboflavin;Riboflavin 5'-monophosphate;Riboflavin 5'-phosphate;Riboflavin mononucleotide;Riboflavin monophosphate;Riboflavin phosphate;Riboflavin-5'-phosphate na;Riboflavin-5-phosphate;Riboflavine 5'-monophosphate;Riboflavine 5'-phosphate;Riboflavine dihydrogen phosphate;Riboflavine monophosphate;Riboflavine phosphate;Riboflavine-5'-phosphate;Vitamin b2 phosphate;Flavin mononucleotide;Riboflavin 5'-(dihydrogen phosphate)PW_C001170FlvnMnt5398119014169224961315772101119002111231322577519115775901117873013212043340512045412212192912412306737612308813512448211812569829712610429912719020512731220912768638819TetrahydrobiopterinHMDB0000027Tetrahydrobiopterin or BH4 is a cofactor in the synthesis of nitric oxide. In fact it is used by all three human nitric-oxide synthases (NOS) eNOS, nNOS, and iNOS as well as the enzyme glyceryl-ether monooxygenase. It is also essential in the conversion of phenylalanine to tyrosine by the enzyme phenylalanine-4-hydroxylase; the conversion of tyrosine to L-dopa by the enzyme tyrosine hydroxylase; and conversion of tryptophan to 5-hydroxytryptophan via tryptophan hydroxylase. Specifically, tetrahydrobiopterin is a cofactor for tryptophan 5-hydroxylase 1, tyrosine 3-monooxygenase, and phenylalanine hydroxylase all of which are essential for the formation of the neurotransmitters dopamine, noradrenaline and adrenaline. Tetrahydrobiopterin has been proposed to be involved in promotion of neurotransmitter release in the brain and the regulation of human melanogenesis. A defect in BH4 production and/or a defect in the enzyme dihydropteridine reductase (DHPR) causes phenylketonuria type IV, as well as dopa-responsive dystonias. BH4 is also implicated in Parkinson's disease, Alzheimer's disease and depression. Tetrahydrobiopterin is present in probably every cell or tissue of higher animals. On the other hand, most bacteria, fungi and plants do not synthesize tetrahydrobiopterin. -- Wikipedia.17528-72-2C00272112515372TETRA-H-BIOPTERIN1093DB00360CC(O)C(O)C1CNC2=C(N1)C(=O)N=C(N)N2C9H15N5O3InChI=1S/C9H15N5O3/c1-3(15)6(16)4-2-11-7-5(12-4)8(17)14-9(10)13-7/h3-4,6,12,15-16H,2H2,1H3,(H4,10,11,13,14,17)FNKQXYHWGSIFBK-UHFFFAOYSA-N2-amino-6-(1,2-dihydroxypropyl)-1,4,5,6,7,8-hexahydropteridin-4-one241.2471241.117489371-2.046tetrahydrobiopterin00FDB021880(1r,2s)-(2-amino-3,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)-1,2-propandiol;2-amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydoro-4(1h)-5,6,7,8-tetrahydro-2-amino-6-(1,2-dihydroxypropyl)-4(1h)-pteridinone;2-amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(1h)-pteridinone;5,6,7,8-erythro-tetrahydrobiopterin;5,6,7,8-tetra-h-biopterin;5,6,7,8-tetrahydro-2-amino-6-(1,2-dihydroxypropyl)-4(1h)-pteridinone;5,6,7,8-tetrahydrobiopterin;L-erythro-2-amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(3h)-pteridinon;Tetra-h-biopterin;Tetra-hydro-biopterin;Tetrahydrobiopterin;2-amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydoro-4(1h)-pteridinone;Bh4PW_C000019BH419572408584800144803144962311190121177520115786631321204344051216161241230683761241741181264932991275853881104PhosphateHMDB0001429Phosphate is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry, biogeochemistry and ecology. Phosphate (Pi) is an essential component of life. In biological systems, phosphorus is found as a free phosphate ion in solution and is called inorganic phosphate, to distinguish it from phosphates bound in various phosphate esters. Inorganic phosphate is generally denoted Pi and at physiological (neutral) pH primarily consists of a mixture of HPO<sup>2-</sup><sub>4</sub> and H<sub>2</sub>PO<sup>-</sup><sub>4</sub> ions. phosphates are most commonly found in the form of adenosine phosphates, (AMP, ADP and ATP) and in DNA and RNA and can be released by the hydrolysis of ATP or ADP. Similar reactions exist for the other nucleoside diphosphates and triphosphates. Phosphoanhydride bonds in ADP and ATP, or other nucleoside diphosphates and triphosphates, contain high amounts of energy which give them their vital role in all living organisms. Phosphate must be actively transported into cells against its electrochemical gradient. In vertebrates, two unrelated families of Na+-dependent Pi transporters carry out this task. Remarkably, the two families transport different Pi species: whereas type II Na+/Pi cotransporters (SCL34) prefer divalent HPO4(2), type III Na+/Pi cotransporters (SLC20) transport monovalent H2PO4. The SCL34 family comprises both electrogenic and electroneutral members that are expressed in various epithelia and other polarized cells. Through regulated activity in apical membranes of the gut and kidney, they maintain body Pi homeostasis, and in salivary and mammary glands, liver, and testes they play a role in modulating the Pi content of luminal fluids. Phosphate levels in the blood play an important role in hormone signaling and in bone homeostasis. In classical endocrine regulation, low serum phosphate induces the renal production of the seco-steroid hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3).This active metabolite of vitamin D acts to restore circulating mineral (i.e. phosphate and calcium) levels by increasing absorption in the intestine, reabsorption in the kidney, and mobilization of calcium and phosphate from bone. Thus, chronic renal failure is associated with hyperparathyroidism, which in turn contributes to osteomalacia (softening of the bones). Another complication of chronic renal failure is hyperphosphatemia (low levels of phosphate in the blood). Hyperphosphatemia (excess levels of phosphate in the blood) is a prevalent condition in kidney dialysis patients and is associated with increased risk of mortality. Hypophosphatemia (hungry bone syndrome) has been associated to postoperative electrolyte aberrations and after parathyroidectomy. (PMID: 17581921, 11169009, 11039261, 9159312, 17625581)Fibroblast growth factor 23 (FGF-23) has recently been recognized as a key mediator of phosphate homeostasis, its most notable effect being promotion of phosphate excretion. FGF-23 was discovered to be involved in diseases such as autosomal dominant hypophosphatemic rickets, X-linked hypophosphatemia, and tumor-induced osteomalacia in which phosphate wasting was coupled to inappropriately low levels of 1,25(OH)2D3. FGF-23 is regulated by dietary phosphate in humans. In particular it was found that phosphate restriction decreased FGF-23, and phosphate loading increased FGF-23.14265-44-2C00009106118367CPD-85871032[O-]P([O-])([O-])=OO4PInChI=1S/H3O4P/c1-5(2,3)4/h(H3,1,2,3,4)/p-3NBIIXXVUZAFLBC-UHFFFAOYSA-Kphosphoric acid94.971494.953423phosphoric acid0-2DBMET00532FDB022617Nfb orthophosphate;O-phosphoric acid;Ortho-phosphate;Orthophosphate (po43-);Orthophosphate(3-);Phosphate;Phosphate (po43-);Phosphate anion(3-);Phosphate ion (po43-);Phosphate ion(3-);Phosphate trianion;Phosphate(3-);Phosphoric acid ion(3-);Pi;[po4](3-);Orthophosphate;Phosphate ion;Po4(3-);Phosphoric acid;Orthophosphoric acid;Phosphoric acid ionPW_C001104Pi2448488145818188312980317631417674925001027294727374631292931667236366138512342492244753150312751587520797521610053171115351112538110354471205543129557313356051355625108569365848143585514659111475941151604015561001616294107648717866911016714117684218868891607161205718920672122117306198738921074022127436163747522281962258258227101182411013425711748132117611151177321311904170119271641201428112728290132632233481917422553044235031542435318436923227701825377194293772171347794033677966130780483327805732978245353786693318002236889279308938313839479638411055839011064039111323594115845398116206109119982406120069122120699407121057124121216125121268429121352121121409123121423382121852405123304119123621118123786136123838464123968447123981399124405376124948472125362479125446297125774481125954299126221478126594300126604298126723484126904501127413388127783209128166395128177513128315389723CitrullineHMDB0000904Citrulline is an amino acid made from ornithine and carbamoyl phosphate in one of the central reactions in the urea cycle. It is also produced from arginine as a by-product of the reaction catalyzed by NOS family (NOS). In this reaction, arginine is first oxidized into N(omega)-hydroxyarginine, which is then further oxidized to citrulline concomitant with the release of nitric oxide (EC 1.14.13.39). Citrulline's name is derived from citrullus, the Latin word for watermelon, from which it was first isolated.372-75-8C00327699209816349L-CITRULLINE9367DB00155N[C@@H](CCCNC(N)=O)C(O)=OC6H13N3O3InChI=1S/C6H13N3O3/c7-4(5(10)11)2-1-3-9-6(8)12/h4H,1-3,7H2,(H,10,11)(H3,8,9,12)/t4-/m0/s1RHGKLRLOHDJJDR-BYPYZUCNSA-N(2S)-2-amino-5-(carbamoylamino)pentanoic acid175.1857175.095691297-0.904L-citrulline00FDB011841(2s)-2-amino-5-(carbamoylamino)pentanoate;(2s)-2-amino-5-(carbamoylamino)pentanoic acid;(s)-2-amino-5-ureidopentanoate;(s)-2-amino-5-ureidopentanoic acid;(s)-2-amino-5-(aminocarbonyl)aminopentanoate;(s)-2-amino-5-(aminocarbonyl)aminopentanoic acid;2-amino-5-uredovalerate;2-amino-5-uredovaleric acid;2-amino-5-ureidovalerate;2-amino-5-ureidovaleric acid;A-amino-d-ureidovalerate;A-amino-d-ureidovaleric acid;Amino-ureidovalerate;Amino-ureidovaleric acid;Cir;Cit;Cytrulline;D-ureidonorvaline;Dl-citrulline;Gammaureidonorvaline;H-cit-oh;L(+)-2-amino-5-ureidovalerate;L(+)-2-amino-5-ureidovaleric acid;L(+)-citrulline;L-2-amino-5-ureido-valerate;L-2-amino-5-ureido-valeric acid;L-2-amino-5-ureidovalerate;L-2-amino-5-ureidovaleric acid;L-citrulline;L-cytrulline;L-n5-carbamoyl-ornithine;N()-carbamylornithine;N(5)-(aminocarbonyl)-dl-ornithine;N(delta)-carbamylornithine;N-carbamylornithine;N5-(aminocarbonyl)-l-ornithine;N5-(aminocarbonyl)ornithine;N5-(aminocarbonyl)-ornithine;N5-carbamoyl-l-ornithine;N5-carbamoylornithine;N5-carbamylornithine;N<sup>5</sup>-(aminocarbonyl)ornithine;Nd-carbamylornithine;Ndelta-carbamy-ornithine;Ndelta-carbamylornithine;Ngamma-carbamylornithine;Sitrulline;Ureidonorvaline;Ureidovalerate;Ureidovaleric acid;Alpha-amino-delta-ureidovalerate;Alpha-amino-delta-ureidovaleric acid;Alpha-amino-gamma-ureidovalerate;Alpha-amino-gamma-ureidovaleric acid;Delta-ureidonorvaline;Citrulline;N(5)-(aminocarbonyl)-l-ornithine;A-amino-delta-ureidovalerate;A-amino-delta-ureidovaleric acid;α-amino-δ-ureidovalerate;α-amino-δ-ureidovaleric acid;δ-ureidonorvaline;N(δ)-carbamylornithine;A-amino-δ-ureidovalerate;A-amino-δ-ureidovaleric acidPW_C000723Citruln7281304411844198118811611270029077464111774951331200801221204034061228281351230461201254522971269912051867Nitric oxideHMDB0003378The biologically active molecule nitric oxide (NO) is a simple, membrane-permeable gas with unique chemistry. It is formed by the conversion of L-arginine to L-citrulline, with the release of NO. The enzymatic oxidation of L-arginine to L-citrulline takes place in the presence of oxygen and NADPH using flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), heme, thiol, and tetrahydrobiopterin as cofactors. The enzyme responsible for the generation of NO is nitric oxide synthase (E.C. 1.7.99.7; NOS). Three NOS isoforms have been described and shown to be encoded on three distinct genes: neuronal NOS (nNOS, NOS type I), inducible NOS (NOS type II), and endothelial NOS (eNOS, NOS type III). Two of them are constitutively expressed and dependent on the presence of calcium ions and calmodulin to function (nNOS and eNOS), while iNOS is considered non-constitutive and calcium-independent. However, experience has shown that constitutive expression of nNOS and eNOS is not as rigid as previously thought (i.e. either present or absent), but can be dynamically controlled during development and in response to injury. Functionally, NO may act as a hormone, neurotransmitter, paracrine messenger, mediator, cytoprotective molecule, and cytotoxic molecule. NO has multiple cellular molecular targets. It influences the activity of transcription factors, modulates upstream signaling cascades, mRNA stability and translation, and processes the primary gene products. In the brain, many processes are linked to NO. NO activates its receptor, soluble guanylate cyclase by binding to it. The stimulation of this enzyme leads to increased synthesis of the second messenger, cGMP, which in turn activates cGMP-dependent kinases in target cells. NO exerts a strong influence on glutamatergic neurotransmission by directly interacting with the N-methyl-D-aspartate (NMDA) receptor. Neuronal NOS is connected to NMDA receptors (see below) and sharply increases NO production following activation of this receptor. Thus, the level of endogenously produced NO around NMDA synapses reflects the activity of glutamate-mediated neurotransmission. However, there is recent evidence showing that non-NMDA glutamate receptors (i.e. AMPA and type I metabotropic receptors) also contribute to NO generation. Besides its influence on glutamate, NO is known to have effects on the storage, uptake and/or release of most other neurotransmitters in the CNS (acetylcholine, dopamine, noradrenaline, GABA, taurine, and glycine) as well as of certain neuropeptides. Finally, since NO is a highly diffusible molecule, it may reach extrasynaptic receptors at target cell membranes that are some distance away from the place of NO synthesis. NO is thus capable of mediating both synaptic and nonsynaptic communication processes. NO is a potent vasodilator (a major endogenous regulator of vascular tone), and an important endothelium-dependent relaxing factor. NO is synthesized by NO synthases (NOS) and NOS are inhibited by asymmetrical dimethylarginine (ADMA). ADMA is metabolized by dimethylarginine dimethylaminohydrolase (DDAH) and excreted in the kidneys. Lower ADMA levels in pregnant women compared to non-pregnant controls suggest that ADMA has a role in vascular dilatation and blood pressure changes. Several studies show an increase in ADMA levels in pregnancies complicated with preeclampsia. Elevated ADMA levels in preeclampsia are seen before clinical symptoms have developed; these findings suggest that ADMA has a role in the pathogenesis of preeclampsia. In some pulmonary hypertensive states such as ARDS, the production of endogenous NO may be impaired. Nitric oxide inhalation selectively dilates the pulmonary circulation. Significant systemic vasodilation does not occur because NO is inactivated by rapidly binding to hemoglobin. In an injured lung with pulmonary hypertension, inhaled NO produces local vasodilation of well-ventilated lung units and may "steal" blood flow away from unventilated regions. This reduces intrapulmonary shunting and may improve systemic arterial oxygenation. Nitric oxide is a chemical mediator fundamental in the maintenance of adequate tissue perfusion and effective cardiovascular function. The use of nitrates is well established as pharmacological agents but it is only recently that it has been recognized that they act as a source of nitric oxide (PMID: 16966108, 8752507, 17181668, 16005189). Nitric oxide is used as a food additive (EAFUS: Everything Added to Food in the United States).10102-43-9C0053314506816480NITRIC-OXIDE127983DB00435[N]=ONOInChI=1S/NO/c1-2MWUXSHHQAYIFBG-UHFFFAOYSA-Nnitroso30.006129.9979886270nitric oxide00FDB021825Mononitrogen monoxide;Nitric oxide;Nitrogen monoxide;Nitrogen oxide;Nitrogen protoxide;Nitrosyl hydride;Nitrosyl radical;Nitroxide radical;Nitroxyl;(no)(.);[no];Edrf;Endothelium-derived relaxing factor;Monoxido de nitrogeno;Monoxyde d'azote;Nitrogen monooxide;Nitrosyl;No;(.)no;No(.);Oxido de nitrogeno(ii);Oxido nitrico;Oxyde azotique;Oxyde nitrique;Stickstoff(ii)-oxid;StickstoffmonoxidPW_C001867NO4795144799141189621177514115803318120428405123062376396L-ArginineHMDB0000517Arginine is an essential amino acid that is physiologically active in the L-form. In mammals, arginine is formally classified as a semi-essential or conditionally essential amino acid, depending on the developmental stage and health status of the individual. Infants are unable to effectively synthesize arginine, making it nutritionally essential for infants. Adults, however, are able to synthesize arginine in the urea cycle. Arginine can be considered to be a basic amino acid as the part of the side chain nearest to the backbone is long, carbon-containing, and hydrophobic, whereas the end of the side chain is a complex guanidinium group. With a pKa of 12.48, the guanidinium group is positively charged in neutral, acidic, and even most basic environments. Because of the conjugation between the double bond and the nitrogen lone pairs, the positive charge is delocalized. This group is able to form multiple H-bonds. L-Arginine is an amino acid that has numerous functions in the body. It helps dispose of ammonia, is used to make compounds such as nitric oxide, creatine, L-glutamate, and L-proline, and it can be converted into glucose and glycogen if needed. In large doses, L-arginine also stimulates the release of the hormones growth hormone and prolactin. Arginine is a known inducer of mTOR (mammalian target of rapamycin) and is responsible for inducing protein synthesis through the mTOR pathway. mTOR inhibition by rapamycin partially reduces arginine-induced protein synthesis (PMID: 20841502). Catabolic disease states such as sepsis, injury, and cancer cause an increase in arginine utilization, which can exceed normal body production, leading to arginine depletion. Arginine also activates AMP kinase (AMPK) which then stimulates skeletal muscle fatty acid oxidation and muscle glucose uptake, thereby increasing insulin secretion by pancreatic beta-cells (PMID: 21311355). Arginine is found in plant and animal proteins, such as dairy products, meat, poultry, fish, and nuts. The ratio of L-arginine to lysine is also important: soy and other plant proteins have more L-arginine than animal sources of protein.74-79-3C000622878216467ARG6082DB00125N[C@@H](CCCNC(N)=N)C(O)=OC6H14N4O2InChI=1S/C6H14N4O2/c7-4(5(11)12)2-1-3-10-6(8)9/h4H,1-3,7H2,(H,11,12)(H4,8,9,10)/t4-/m0/s1ODKSFYDXXFIFQN-BYPYZUCNSA-N(2S)-2-amino-5-carbamimidamidopentanoic acid174.201174.111675712-1.885L-arginine01DBMET00502FDB002257(s)-2-amino-5-[(aminoiminomethyl)amino]pentanoate;(s)-2-amino-5-[(aminoiminomethyl)amino]pentanoic acid;(s)-2-amino-5-[(aminoiminomethyl)amino]-pentanoate;(s)-2-amino-5-[(aminoiminomethyl)amino]-pentanoic acid;2-amino-5-guanidinovalerate;2-amino-5-guanidinovaleric acid;5-[(aminoiminomethyl)amino]-l-norvaline;Arginine;L-(+)-arginine;L-a-amino-d-guanidinovalerate;L-a-amino-d-guanidinovaleric acid;L-alpha-amino-delta-guanidinovalerate;L-alpha-amino-delta-guanidinovaleric acid;N5-(aminoiminomethyl)-l-ornithine;(2s)-2-amino-5-(carbamimidamido)pentanoic acid;(2s)-2-amino-5-guanidinopentanoic acid;(s)-2-amino-5-guanidinopentanoic acid;(s)-2-amino-5-guanidinovaleric acid;Arg;L-arg;L-arginin;R;(2s)-2-amino-5-(carbamimidamido)pentanoate;(2s)-2-amino-5-guanidinopentanoate;(s)-2-amino-5-guanidinopentanoate;(s)-2-amino-5-guanidinovaleratePW_C000396Arg1058344835620107562311711846198127322904253132242554318774671117809511279239293792401641200561221221424071228081351246941191254342971262994811269732051278632061155Inositol 1,4,5-trisphosphateHMDB0001498Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. (PubChem). Inositol 1,4,5-trisphosphate (InsP3) is traditionally considered to be the messenger that initiates the increase and spreading of the activating Ca2+ wave. In line with this hypothesis, recent evidence suggests that the penetrating sperm delivers into mammalian eggs a novel isoform of phospholipase C (PLC), which promotes the formation of InsP3. The mechanism by which the interacting sperm triggers the production of NAADP and subsequently that of InsP3 remains obscure. (PMID: 15362223).85166-31-0C0124543945616595inositol_1,4,5-trisphosphate388562O[C@@H]1[C@H](O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H](O)[C@@H]1OP(O)(O)=OC6H15O15P3InChI=1S/C6H15O15P3/c7-1-2(8)5(20-23(13,14)15)6(21-24(16,17)18)3(9)4(1)19-22(10,11)12/h1-9H,(H2,10,11,12)(H2,13,14,15)(H2,16,17,18)/t1-,2+,3+,4-,5-,6-/m1/s1MMWCIQZXVOZEGG-XJTPDSDZSA-N{[(1R,2S,3R,4R,5S,6R)-2,3,5-trihydroxy-4,6-bis(phosphonooxy)cyclohexyl]oxy}phosphonic acid420.0956419.962379346-1.459InsP30-6FDB0226571d-myo-inositol 1,4,5-trisphosphate;D-myo-inositol 1,4,5-trisphosphate;Inositol 1,4,5-trisphosphate;1,4,5-insp3;D-myo-inositol-1,4,5-triphosphate;Ins(1,4,5)p3;Insp3;Ip3;1d-myo-inositol 1,4,5-trisphosphoric acid;D-myo-inositol 1,4,5-trisphosphoric acid;D-myo-inositol-1,4,5-triphosphoric acid;Inositol 1,4,5-trisphosphoric acidPW_C001155Inotp27416658220372325751427924673871607409218122142856934417816912878211132785161157999918800893088023781219754101224421241225114051245284441250091181250813761261244851265932991266644781277325161281653881282412099201NitroglycerinHMDB0014865Nitroglycerin is only found in individuals that have used or taken this drug. It is a volatile vasodilator which relieves angina pectoris by stimulating guanylate cyclase and lowering cytosolic calcium. [PubChem]Similar to other nitrites and organic nitrates, nitroglycerin is converted to nitric oxide (NO), an active intermediate compound which activates the enzyme guanylate cyclase. This stimulates the synthesis of cyclic guanosine 3',5'-monophosphate (cGMP) which then activates a series of protein kinase-dependent phosphorylations in the smooth muscle cells, eventually resulting in the dephosphorylation of the myosin light chain of the smooth muscle fiber. The subsequent release of calcium ions results in the relaxation of the smooth muscle cells and vasodilation.55-63-0C074554510287874354DB00727[O-][N+](=O)OCC(CO[N+]([O-])=O)O[N+]([O-])=OC3H5N3O9InChI=1S/C3H5N3O9/c7-4(8)13-1-3(15-6(11)12)2-14-5(9)10/h3H,1-2H2SNIOPGDIGTZGOP-UHFFFAOYSA-N1,3-bis(nitrooxy)propan-2-yl nitrate227.0865227.002578773-3.050nitroglycerin00Glyceryl trinitrate;Ng;Ntg;Nitroglycerin ointment;Nitroglycerine;Tng;Trinitroglycerin;1,2,3-propanetrioltrinitrate;1,2,3-propanetriyl nitrate;Glycerin trinitrate;Glycerol trinitrate;Glycerol, nitric acid triester;Minitran;Natispray;Nitro-dur;Nitroglycerol;Nitrolingual;Nitromist;Nitrostat;Propane-1,2,3-triyl trinitrate;Rectogesic;Transderm nitro;Trinitroglycerol;1,2,3-propanetrioltrinitric acid;1,2,3-propanetriyl nitric acid;Glycerin trinitric acid;Glycerol trinitric acid;Glycerol, nitrate triester;Glyceryl trinitric acid;Propane-1,2,3-triyl trinitric acidPW_C009201NitoGly104596Glyceryl 1,2-dinitrateGlyceryl 1,2-dinitrate has the chemical formula C3H6N2O7, and an average molecular weight of 182.088. Glyceryl 1,2-dinitrate is involved in the Nitric Oxide Signaling Pathway.79076OCC(CO[N+]([O-])=O)O[N+]([O-])=OC3H6N2O7InChI=1S/C3H6N2O7/c6-1-3(12-5(9)10)2-11-4(7)8/h3,6H,1-2H2GFVHBTOOPNJKLV-UHFFFAOYSA-N2,3-bis(nitrooxy)propan-1-ol182.088182.017500541-2.231glyceryl-1,2-dinitrate00PW_C104596G12D135491181706NitriteHMDB0002786Nitrite is a nitrite compound is either a salt or an ester of nitrous acid. Sodium nitrite is used for the curing of meat because it prevents bacterial growth and, in a reaction with the meat's myoglobin, gives the product a desirable dark red color. Nitrite can be reduced to nitric oxide or ammonia by many species of bacteria. Under hypoxic conditions, nitrite may release nitric oxide, which causes potent vasodilation. Several mechanisms for nitrite conversion to NO have been described including enzymatic reduction by xanthine oxidoreductase, the mitochondria, and NO synthase (NOS), as well as nonenzymatic acidic disproportionation. -- Wikipedia.14797-65-0C0008894616301NITRITE921ON=OHNO2InChI=1S/HNO2/c2-1-3/h(H,2,3)IOVCWXUNBOPUCH-UHFFFAOYSA-Nnitrous acid47.013447.0007282811nitrous acid00FDB023064Nitrite;Nitrite anion;Nitrite ion;Nitrogen dioxide;Nitrogen dioxide ion;Nitrogen peroxide ion;[no2](-);Nitrit;Nitrite(1-);Nitrous acid, ion(1-);No2(-)PW_C001706NO26513107651410867911174231931842320315437603221515Glutamate [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 receptorsHMDBP01635GRIN19q34.3L056661327673132159141520Glutamate [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 subunitsHMDBP01642GRIN2A16p13.2U090021327773132158143065Glutamate [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 mechanismHMDBP07845GRIN3A9q31.1AB07585313278731321631414387Disks large homolog 4P78352
Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B. Also regulates AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic density keeping the channels in an activated state in the presence of glutamate and preventing synaptic depression.
DLG4180248228802508871Nitric oxide synthase, brainP29475Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR.
HMDBP00928NOS112q24.2-q24.31U1730811.14.13.39408884802144804141597Calmodulin-1P0DP23
Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).
HMDBP01777CALM114q24-q31AC0732831998212774468026081360715013613565314388Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoformQ08209
Calcium-dependent, calmodulin-stimulated protein phosphatase. Many of the substrates contain a PxIxIT motif. This subunit may have a role in the calmodulin activation of calcineurin. Dephosphorylates DNM1L, HSPB1 and SSH1.
PPP3CA13.1.3.1680256228802572780259814389Protein kinase C alpha typeP17252
Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42 (PubMed:28028151). Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription.
PRKCA12.7.11.1380261880262278026323114390cAMP-dependent protein kinase catalytic subunit betaP22694
Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (PubMed:12420224, PubMed:21423175). Phosphorylates GPKOW which regulates its ability to bind RNA (PubMed:21880142).
PRKACB12.7.11.11802641480265278026682126Inositol 1,4,5-trisphosphate receptor type 1Q14643Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5- trisphosphateHMDBP02849ITPR13p26.1D26070196716279418850210800918136138654289Aldehyde dehydrogenase, mitochondrialP05091HMDBP00295ALDH212q24.2K0300111.2.1.3547413218187133009213549218176Xanthine dehydrogenase/oxidaseP47989Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro).
HMDBP00181XDH2p23.1U3948711.17.1.4; 1.17.3.26292818725374824003848319496431782Glutamate receptor ionotropic1PW_P0007828851515188615201887306517576Disks large homolog 41PW_P007576154591438780249228940Nitric-oxide synthase, brain1PW_P0009401065871238717991388964138911701390191223Calmodulin1PW_P00022324115977577Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform1PW_P00757715460143888025887578PKA-PKC1PW_P00757815461143891546214390270Inositol 1,4,5-trisphosphate receptor type 11PW_P00027028921264159Aldehyde dehydrogenase, mitochondrial1PW_P000159177289454543401Xanthine oxidase1PW_P003401101451761179133PW_R179133Right67576892011Compoundfalse6757691045961Compoundfalse67577017061Compoundfalse1690341591.2.1.3179134PW_R179134Right67577117061Compoundfalse67577218671Compoundfalse16903534011158PW_T001158Active13963531Compound158Right9777822018-06-18T15:19:52-06:002018-06-18T15:19:52-06:00228390ActivationPW_I0003907797576ProteinComplex1780940ProteinComplex1392ActivationPW_I000392783223ProteinComplex1784940ProteinComplex1391ActivationPW_I000391781940ProteinComplex17827577ProteinComplex1393ActivationPW_I0003937857578ProteinComplex1786940ProteinComplex1395ActivationPW_I0003957897577ProteinComplex1790940ProteinComplex1746ActivationPW_I0007461491723Compound11492940ProteinComplex1747ActivationPW_I0007471493940ProteinComplex114941867Compound1748ActivationPW_I0007481495940ProteinComplex11496396Compound1242ActivationPW_I0002424831155Compound1484270ProteinComplex115880533531551false122310010regular78781588054353851false122374310regular78781588055179989true60333010regular10025158805696489true60331010regular100251588057117089true60328010regular1003515880581989true60326010regular100251588064179989true54873510regular10025158806596489true54874010regular100251588066117089true54874510regular1003515880671989true54875010regular10025158808535351false143566010regular7878158808635351false108511010regular7878158808735351false134512010regular78781588089110446false65833510regular44431588090110446false87350810regular4443158809235351false129076510regular7878159027072383false79864010regular10010015902771867864false50981510regular7878159027839683false26881510regular10010026741771155183false219764310regular10012026741789201183false1160110110regular1001002674179104596183false745102910regular10011026741801706183false660115910regular100100594419151576false10482588subunitregular15070594420152076false11882588subunitregular15070594421306576false13232588subunitregular1507059442214387880false6582308subunitregular20013059442387182false6533608subunitregular15070594426159782false11638158subunitregular150705944281438882false6534958subunitregular150705944291438982false2333578subunitregular150705944301439082false2334078subunitregular1507059443587182false4736208subunitregular1507059444315972false14009458subunitregular150709462162126188false18976608subunitregular14085946217289188false91511148subunitregular140859462181762false6348198subunitregular15070482617782645155931085944195931095944205931105944214826187576645158593111594422482619940645158593112594423808515880552164737Cofactor808615880562164738Cofactor808715880572164739Cofactor808815880582164740Cofactor48262222364515859311559442648262475776451585931175944284826257578645158593118594429593119594430482628940645158593122594435809315880642164769Cofactor809415880652164770Cofactor809515880662164771Cofactor809615880672164772Cofactor801626270645151894228294621680162715964515189422839462178016283401645159422849462182164734M1262 178 C1262 208 1263 228 1263 258 83false18falsefalse2164735M1262 743 C1262 713 1263 358 1263 328 83false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false2164736M1261 846 C1231 846 1262 840.5 1237 851.5 149true12164737M408 325 L408 375 L458 325 z10true182164738M408 305 L408 355 L458 305 z10true182164739M408 275 L408 325 L458 275 z10true182164740M408 255 L408 305 L458 255 z10true182164741M1242 845 C1247 847 1219 879 1247 844 149true1trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false2164746M1163 850 C1075 851 1009 850.25 952 849.25 C952 721.25 953 461.25 952 394.25 C910 394.25 851 395 803 395 149false182164747M798 390 C821 388 939 392.25 954 391.25 149true18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false2164750M1247 857 C1247 887 1243 826.25 1243 856.25 149true12164751M728 495 C728 465 728 460 728 430 149false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false2164760M1240 849 C1270 849 1237.5 869.5 1233.5 839.5 149true12164761M653 395 C384 392 653 395 383 392 149false18trueM 25.946855044164835 59.26155629629604 L 11 58 L 17.380887721185843 71.57513432307834false2164768M1246 861 C1246 891 1245 801.75 1243 867.75 149true12164769M543 730 L543 780 L593 730 z10true182164770M543 735 L543 785 L593 735 z10true182164771M543 740 L543 790 L593 740 z10true182164772M543 745 L543 795 L593 745 z10true182164773M623 655 C640 656 688 657 728 656 C728 613 728 616 728 565 149false18trueM 25.946855044164835 123.26155629629604 L 11 122 L 17.380887721185843 135.57513432307834false2164774M308 477 C308 532 308 605 307 653 C369 654 409 654 473 655 149false18trueM 89.94685504416483 533.261556296296 L 75 532 L 81.38088772118584 545.5751343230784false2164789M1313 850 C1325 851 1446 851 1474 851 C1473 840 1474 739 1474 738 149false18trueM 1082.2063572806082 494.785281710068 L 1073.5 507 L 1088.4314349794556 508.4325674344643false2164795M803 530 C821 530 836 529.5 873 529.5 149false18trueM 567.2033013768963 703.2112415275712 L 582 700.75 L 572.4701530007222 689.1663038640356false2164796M1313 850 C1317 850 1473 849 1474 850 C1474 849 1476 946 1475 945 149false18trueM 974.9468550441649 471.261556296296 L 960 470 L 966.3808877211858 483.5751343230783false2165891M548 893 C549 893 548 964 548 976 149false18trueM 397.06440098298674 1245.611518094107 L 412 1247 L 405.73466109469183 1233.371150877582false2169933M798 690 C766 690 590 692 548 690 149false18trueM 687.5533425419412 903.9598072232907 L 678.5 892 L 672.6691743912362 905.8203282421289false2169934M623 655 C653 655 655.5 760 685.5 760 149true18trueM 128.44685504416483 614.511556296296 L 113.5 613.25 L 119.88088772118584 626.8251343230784false2169981M548 815 C548 785 548 720 548 690 149false18trueM 128.44685504416483 614.511556296296 L 113.5 613.25 L 119.88088772118584 626.8251343230784false2169982M598 700 C598 730 656 759 598 782 149true182169983M318 815 C318 776 317 743 318 689 C367 689 497 688 548 690 149false18trueM 128.44685504416483 614.511556296296 L 113.5 613.25 L 119.88088772118584 626.8251343230784false2169984M720 729 C720 759 623 732.5 623 762.5 149true183651249M1513 699 C1539 699 1759 698 1789 697 5false18trueM 1525.9903810567666 691.5 L 1513 699 L 1525.9903810567666 706.5false3651251M2297 703 C2327 703 1832 633 1862 633 149true183651252M2037 700 C2094 699 2137 704 2197 703 149false18trueM 637.9468550441649 356.261556296296 L 623 355 L 629.3808877211858 368.5751343230783false3651253M1160 1151 C1132 1151 1082 1154 1055 1154 5false183651254M845 1084 C905 1084 867 1084 915 1084 C916 1117 915 1131 915 1154 5false18trueM 35.946855044164835 362.261556296296 L 21 361 L 27.380887721185843 374.5751343230783false3651255M760 1209 C792 1209 874 1209 915 1209 C917 1185 914 1169 915 1154 5false18trueM 35.946855044164835 362.261556296296 L 21 361 L 27.380887721185843 374.5751343230783false3651256M710 1159 C711 1110 709 927 709 889 5false183651257M587 854 C639 854 613 853 634 854 5false18trueM 25.946855044164835 597.261556296296 L 11 596 L 17.380887721185843 609.5751343230784false7960026451517913318321798726741783651253Left321798826741793651254Right321798926741803651255Right75189716903480162779600364515179134321799026741803651256Left321799115902773651257Right751898169035801628229871158645154669715880532164734Left4669815880542164735Right22425482617977157039064515815764826182164736Left15774826192164741Right157339264515815824826222164746Left15834826192164747Right157539164515815864826192164750Left15874826242164751Right157639364515815884826252164760Left15894826192164761Right157839564515815924826242164768Left15934826282164773Right215874664515870915902702169933Left25464826282169934Right217874764515871015902772169981Right25854826282169982Left217974864515871115902782169983Right25864826282169984Left75822426451518175426741773651251Left89868016263651252Right839158808584015880868411588087843158808984415880908461588092635092164774635122164789635142164795635152164796635512165891681213651249133659444318592917225151.01.0023280360185930136210861.01.0021490240220366M125 389 C125 339 175 289 225 289 C835 289 1628 289 2238 289 C2288 289 2338 339 2338 389 C2338 702 2338 1108 2338 1421 C2338 1471 2288 1521 2238 1521 C1628 1521 835 1521 225 1521 C175 1521 125 1471 125 1421 C125 1108 125 702 125 389 1true12213.01232.024532615cCMP Regulation Long-Term Potentiation Neurotransmission463960201.01.01601524538115Extracellular228195201.31.31601524538215Cytoplasm223283201.31.31601544992715IP3 binds to receptors on the endoplasmic reticulum and causes Ca2+ release from intracellular stores1769733201.01.0160151802421479120063710111288128840#FFEBEB4651277