357PathwayDopamine Activation of Neurological Reward SystemIn the nervous system, dopamine acts as a neurotransmitter with roles in motor control, motivation, arousal, cognition, and reward. The mesolimbic pathway is the main pathway associated with reward, and the dopaminergic neurons of this pathway are found in the substantia nigra (SNc) and ventral tegmental area (VTA) of the midbrain. Dopamine acts on different G protein-coupled receptor subtyes. The D1-class (D1 and D5) receptors stimulate cAMP production by activating adenylyl cyclase, which activates the reward pathway. The D2-class (D2, D3, and D4) subtypes act oppositely, inhibiting cAMP production by inhibiting adenylyl cyclase. The differing distributions of the receptor subtypes mean that complex outputs often produce a synergistic effect, despite the receptor subtypes having opposite molecular effects (PMID: 20925949, 21303898).SignalingPW000440TopPathwayVisualizationContext45616593358#000099PathwayVisualization340357Dopamine Activation of Neurological Reward SystemIn the nervous system, dopamine acts as a neurotransmitter with roles in motor control, motivation, arousal, cognition, and reward. The mesolimbic pathway is the main pathway associated with reward, and the dopaminergic neurons of this pathway are found in the substantia nigra (SNc) and ventral tegmental area (VTA) of the midbrain. Dopamine acts on different G protein-coupled receptor subtyes. The D1-class (D1 and D5) receptors stimulate cAMP production by activating adenylyl cyclase, which activates the reward pathway. The D2-class (D2, D3, and D4) subtypes act oppositely, inhibiting cAMP production by inhibiting adenylyl cyclase. The differing distributions of the receptor subtypes mean that complex outputs often produce a synergistic effect, despite the receptor subtypes having opposite molecular effects (PMID: 20925949, 21303898).Signaling1671Reward SystemSubPathway1114922ProteinComplex22801072648975Wise RA, Rompre PP: Brain dopamine and reward. Annu Rev Psychol. 1989;40:191-225. doi: 10.1146/annurev.ps.40.020189.001203.357Pathway28010812383780Schultz W: Getting formal with dopamine and reward. Neuron. 2002 Oct 10;36(2):241-63.357Pathway2801099716927Wise RA: Drug-activation of brain reward pathways. Drug Alcohol Depend. 1998 Jun-Jul;51(1-2):13-22.357Pathway3NeuronCL:00005401CellCL:00000002Platelet CL:00002335HepatocyteCL:00001824Cardiomyocyte CL:00007468Beta cellCL:00006397Epithelial CellCL:00000661Homo sapiens9606EukaryoteHuman4Arabidopsis thaliana3702EukaryoteThale cress12Mus musculus10090EukaryoteMouse2Bacteria2ProkaryoteBacteria5Bos taurus9913EukaryoteCattle17Rattus norvegicus10116EukaryoteRat6Caenorhabditis elegans6239EukaryoteRoundworm3Escherichia coli562Prokaryote24Solanum lycopersicum4081EukaryoteTomato18Saccharomyces cerevisiae4932EukaryoteYeast21Xenopus laevis8355EukaryoteAfrican clawed frog49Bathymodiolus platifrons220390EukaryoteDeep sea mussel60Nitzschia sp.0001EukaryoteNitzschia410Drosophila melanogaster7227EukaryoteFruit fly19Schizosaccharomyces pombe4896Eukaryote25Escherichia coli (strain K12)83333Prokaryote23Pseudomonas aeruginosa287Prokaryote51Picea sitchensis3332EukaryoteSitka spruce56Andro6666Eukaryote5CytoplasmGO:00057371CytosolGO:000582910Cell MembraneGO:000588611Extracellular SpaceGO:00056153Mitochondrial MatrixGO:000575914Mitochondrial Outer MembraneGO:00057412MitochondrionGO:000573915NucleusGO:00056344PeroxisomeGO:000577713Endoplasmic ReticulumGO:00057837Endoplasmic Reticulum MembraneGO:000578927Peroxisome MembraneGO:000577831Periplasmic SpaceGO:000562035ChloroplastGO:000950712Mitochondrial Inner MembraneGO:000574332Inner MembraneGO:007025825Golgi apparatusGO:000579426Golgi apparatus membraneGO:00001393Sympathetic Nervous SystemBTO:00018324Adrenal MedullaBTO:000004971824BrainBTO:000014289162Endothelium BTO:00003931LiverBTO:00007597297Nervous SystemBTO:000148418PancreasBTO:000098825IntestineBTO:00006488Blood VesselBTO:000110274115cardiocyteBTO:000153932Adrenal CortexBTO:0000045193513PW_BS000019204111PW_BS0000202441011PW_BS0000242111PW_BS0000027413PW_BS000074711113PW_BS00007115111PW_BS00001529341PW_BS00002434141121PW_BS000028360410121PW_BS0000281321121PW_BS00013298112PW_BS000098184121PW_BS00002443441051PW_BS000115124151PW_BS000124469410171PW_BS0001151181171PW_BS00011851541061PW_BS000115388161PW_BS0001128511PW_BS0000084311PW_BS00000414101PW_BS000014731013PW_BS00007385241011PW_BS000085103331PW_BS0001031553241PW_BS0001551613181PW_BS0001611783211PW_BS000178222341PW_BS0000241151012PW_BS0001152111018PW_BS0000241985181PW_BS0000242905491PW_BS000024151141PW_BS00015111PW_BS0000011333121PW_BS0001331115121PW_BS0001113683601PW_BS0000283081011PW_BS0000241644PW_BS000164253541PW_BS000024406351PW_BS000115122551PW_BS000122405105PW_BS0001151203171PW_BS0001201355171PW_BS0001353761017PW_BS0000534793101PW_BS0001152975101PW_BS000024501361PW_BS000115205561PW_BS00002416212PW_BS000016221411PW_BS00002213121PW_BS0000133211515PW_BS0000325411PW_BS000005397113PW_BS0000393211PW_BS000003181311PW_BS000018101711PW_BS00001049711PW_BS0000495811411PW_BS000058592711PW_BS00005927151PW_BS00002746114PW_BS00004629111PW_BS0000296618518PW_BS00006672513PW_BS000072612517PW_BS0000615181PW_BS000051231511PW_BS000023311511PW_BS000031918511PW_BS000091541315PW_BS000054892PW_BS000089261115PW_BS000026711PW_BS000007971521PW_BS000097100521PW_BS0001001041431PW_BS000104101531PW_BS0001011122121PW_BS000112117131PW_BS00011712915121PW_BS00012910813PW_BS00010814315191PW_BS0001431465191PW_BS000146107313PW_BS0001071471241PW_BS00014716611PW_BS000166188118PW_BS0000241601181PW_BS00016019914181PW_BS000024206261PW_BS00002421013181PW_BS0000242137181PW_BS0000242164181PW_BS0000242171518PW_BS00002421815181PW_BS0000241632181PW_BS0001631901118PW_BS0000242253541PW_BS0000242771218PW_BS00002417018PW_BS0001702811251PW_BS0000242851041PW_BS000024226441PW_BS0000242231241PW_BS000024315123PW_BS0000243221231PW_BS0000243183123PW_BS00002413412121PW_BS00013432914121PW_BS0000283331212PW_BS0000283361121PW_BS00002833217121PW_BS000028350114121PW_BS00002812815121PW_BS0001283511512PW_BS00002835325127PW_BS00002833527121PW_BS00002813013121PW_BS0001303317121PW_BS0000283344121PW_BS0000281192171PW_BS000119943PW_BS000094109323PW_BS000109407251PW_BS0001153821451PW_BS000100412125PW_BS000115429151PW_BS0001151231751PW_BS00012343311451PW_BS000115408451PW_BS0001154101551PW_BS0001151251351PW_BS000125383751PW_BS0001004222751PW_BS000115435155PW_BS00011539914171PW_BS0001134461217PW_BS0001154641171PW_BS00011544717171PW_BS000115468114171PW_BS0001153744171PW_BS00005344415171PW_BS00011513613171PW_BS0001363987171PW_BS00011347225177PW_BS00011537527171PW_BS0000534701517PW_BS0001152991101PW_BS0000244812101PW_BS00011548414101PW_BS00011548515101PW_BS00011530013101PW_BS0000244957101PW_BS0001154781010PW_BS00011549127101PW_BS0001154991510PW_BS0001153891461PW_BS0001125161561PW_BS0001153951361PW_BS000113390761PW_BS000112209106PW_BS0000245082761PW_BS000115517156PW_BS000115215114PW_BS000021432511PW_BS000043562611PW_BS00005621425181PW_BS0000242491341PW_BS0000242881441PW_BS00002435625121PW_BS000028372102PW_BS0000284192551PW_BS00011545525171PW_BS0001154824101PW_BS00011549025101PW_BS000115502461PW_BS0001155072561PW_BS00011530635511PW_BS000024171211PW_BS0000173841251PW_BS0001003911261PW_BS00011212112171PW_BS000121599856PW_BS000501608321PW_BS0005016651818PW_BS00050852DopamineHMDB0000073Dopamine is a member of the catecholamine family of neurotransmitters in the brain and is a precursor to epinephrine (adrenaline) and norepinephrine (noradrenaline). Dopamine is synthesized in the body (mainly by nervous tissue and adrenal glands) first by the hydration of the amino acid tyrosine to DOPA by tyrosine hydroxylase and then by the decarboxylation of DOPA by aromatic-L-amino-acid decarboxylase. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (dopamine receptors) mediates its action, which plays a major role in reward-motivated behaviour. Dopamine has many other functions outside the brain. In blood vessels, dopamine inhibits norepinephrine release and acts as a vasodilator (at normal concentrations); in the kidneys, it increases sodium excretion and urine output; in the pancreas, it reduces insulin production; in the digestive system, it reduces gastrointestinal motility and protects intestinal mucosa; and in the immune system, it reduces the activity of lymphocytes. Parkinson's disease, a degenerative condition causing tremor and motor impairment, is caused by a loss of dopamine-secreting neurons in an area of the midbrain called the substantia nigra. There is evidence that schizophrenia involves altered levels of dopamine activity, and most antipsychotic drugs used to treat this are dopamine antagonists, which reduce dopamine activity. Attention deficit hyperactivity disorder, bipolar disorder, and addiction are also characterized by defects in dopamine production or metabolism. It has been suggested that animals derived their dopamine-synthesizing machinery from bacteria via horizontal gene transfer that may have occurred relatively late in evolutionary time. This is perhaps a result of the symbiotic incorporation of bacteria into eukaryotic cells that gave rise to mitochondria. Dopamine is elevated in the urine of people who consume bananas. When present in sufficiently high levels, dopamine can be a neurotoxin and a metabotoxin. A neurotoxin is a compound that disrupts or attacks neural tissue. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of dopamine are associated with neuroblastoma, Costello syndrome, leukemia, phaeochromocytoma, aromatic L-amino acid decarboxylase deficiency, and Menkes disease (MNK). High levels of dopamine can lead to hyperactivity, insomnia, agitation and anxiety, depression, delusions, excessive salivation, nausea, and digestive problems.51-61-6C0375868118243DOPAMINE661DB00988NCCC1=CC(O)=C(O)C=C1C8H11NO2InChI=1S/C8H11NO2/c9-4-3-6-1-2-7(10)8(11)5-6/h1-2,5,10-11H,3-4,9H2VYFYYTLLBUKUHU-UHFFFAOYSA-N4-(2-aminoethyl)benzene-1,2-diol153.1784153.078978601-1.313dopamine01FDB0121632-(3,4-dihydroxyphenyl)ethylamine;3,4-dihydroxyphenethylamine;3,4-dihydroxyphenylethylamine;3-hydroxytyramine;4-(2-aminoethyl)-1,2-benzenediol;4-(2-aminoethyl)-pyrocatechol;4-(2-aminoethyl)catechol;4-(2-aminoethyl)pyrocatechol;Deoxyepinephrine;Dopamin;Dopamine;Dopaminum;Dopastat;Dophamine;Dynatra;Hydroxytyramin;Hydroxytyramine;Intropin;Oxytyramine;Revivan;A-(3,4-dihydroxyphenyl)-b-aminoethane;Alpha-(3,4-dihydroxyphenyl)-beta-aminoethane;4-(2-aminoethyl)benzene-1,2-diol;DopaminaPW_C000052LDP40019694202017242080231877431887141611577043293777623417911236079138132800509880051184121606434121637124124164469124195118127575515127611388936Guanosine diphosphateHMDB0001201Guanosine 5'-(trihydrogen diphosphate). A guanine nucleotide containing two phosphate groups esterified to the sugar moiety. It is an ester of pyrophosphoric acid with the nucleoside guanosine. GDP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase guanine. GDP is the product of GTP dephosphorylation by GTPases, e.g. the G-proteins that are involved in signal transduction.146-91-8C00035897717552GDP-4-DEHYDRO-6-DEOXY-D-MANNOSE8630NC1=NC2=C(N=CN2[C@@H]2O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]2O)C(=O)N1C10H15N5O11P2InChI=1S/C10H15N5O11P2/c11-10-13-7-4(8(18)14-10)12-2-15(7)9-6(17)5(16)3(25-9)1-24-28(22,23)26-27(19,20)21/h2-3,5-6,9,16-17H,1H2,(H,22,23)(H2,19,20,21)(H3,11,13,14,18)/t3-,5-,6-,9-/m1/s1QGWNDRXFNXRZMB-UUOKFMHZSA-N[({[(2R,3S,4R,5R)-5-(2-amino-6-oxo-6,9-dihydro-3H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]phosphonic acid443.2005443.024329371-2.007{[(2R,3S,4R,5R)-5-(2-amino-6-oxo-3H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy(hydroxy)phosphoryl}oxyphosphonic acid0-3FDB0224875'-gdp;Gdp;Guanosine 5'-(trihydrogen pyrophosphate);Guanosine 5'-diphosphate;Guanosine 5'-pyrophosphate;Guanosine mono(trihydrogen diphosphate);Guanosine pyrophosphate;Guanosine-5'-diphosphate;Guanosine-diphosphate;Ppg;Guanosine diphosphate;Guanosine 5'-diphosphoric acidPW_C000936GDP83823841762142391241547350078553821036041155610116164881787476222117541151177121111823198127272901339515169322177142133775461117795213280023368800803088012216489115253119983406120068122121205124121847405122766120122820135123775118124400376125363479125445297126905501126984205414Adenosine triphosphateHMDB0000538Adenosine triphosphate (ATP) is a nucleotide consisting of a purine base (adenine) attached to the first carbon atom of ribose (a pentose sugar). Three phosphate groups are esterified at the fifth carbon atom of the ribose. ATP is incorporated into nucleic acids by polymerases in the processes of DNA replication and transcription. ATP contributes to cellular energy charge and participates in overall energy balance, maintaining cellular homeostasis. ATP can act as an extracellular signaling molecule via interactions with specific purinergic receptors to mediate a wide variety of processes as diverse as neurotransmission, inflammation, apoptosis, and bone remodelling. Extracellular ATP and its metabolite adenosine have also been shown to exert a variety of effects on nearly every cell type in human skin, and ATP seems to play a direct role in triggering skin inflammatory, regenerative, and fibrotic responses to mechanical injury, an indirect role in melanocyte proliferation and apoptosis, and a complex role in Langerhans cell-directed adaptive immunity. During exercise, intracellular homeostasis depends on the matching of adenosine triphosphate (ATP) supply and ATP demand. Metabolites play a useful role in communicating the extent of ATP demand to the metabolic supply pathways. Effects as different as proliferation or differentiation, chemotaxis, release of cytokines or lysosomal constituents, and generation of reactive oxygen or nitrogen species are elicited upon stimulation of blood cells with extracellular ATP. The increased concentration of adenosine triphosphate (ATP) in erythrocytes from patients with chronic renal failure (CRF) has been observed in many studies but the mechanism leading to these abnormalities still is controversial. (PMID: 15490415, 15129319, 14707763, 14696970, 11157473).56-65-5C00002595715422ATP5742DB00171NC1=NC=NC2=C1N=CN2[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1OC10H16N5O13P3InChI=1S/C10H16N5O13P3/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(26-10)1-25-30(21,22)28-31(23,24)27-29(18,19)20/h2-4,6-7,10,16-17H,1H2,(H,21,22)(H,23,24)(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1ZKHQWZAMYRWXGA-KQYNXXCUSA-N({[({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)phosphonic acid507.181506.995745159-2.057adenosine triphosphate0-3FDB0218135'-(tetrahydrogen triphosphate) adenosine;5'-atp;Atp;Adenosine 5'-triphosphate;Adenosine 5'-triphosphorate;Adenosine 5'-triphosphoric acid;Adenosine triphosphate;Adenylpyrophosphorate;Adenylpyrophosphoric acid;Adephos;Adetol;Adynol;Atipi;Atriphos;Cardenosine;Fosfobion;Glucobasin;Myotriphos;Phosphobion;Striadyne;Triadenyl;Triphosphaden;Triphosphoric acid adenosine ester;Adenosine-5'-triphosphate;H4atp;Adenosine triphosphoric acid;Adenosine-5'-triphosphoric acidPW_C000414ATP9221460826616414224781373332799593439976321051821121021464921561421605824055924342727264628122930296631637236166136175143992344743147689148645450328950352651557520597521510052501045291101531311153461125390103540611754301185443120554212955561325569133560313556211085846143585414658761075897147592415160481556109161623016664931786839188687016069761997157205718420672092107225213722921172981987302216739021774082187432163748122274991908186225118472771190317012010281120391641217828512578226126912901326422315327308423263154262132242694318770282537721813477233329774683337763233678037332780413507816812878214351782403537841133578494115788501307886533178919334800283688004618480674119856291948261241132349411328238811628010911991412211999240612015440712024538212036241212124642912139212312139743312147140812197441012206512512207938312208340512240242212244443512291939912300944612381646412395144712395646812402937412452744412461613612463039812463437612494347212497237512501147012530429712537147912539229912551548112559548412612348512622030012623449512624047812654749112659649912691350112712338912773151612778139512779639012780120912811950812816751741cAMPHMDB0000058cAMP or cyclic AMP is an adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. cAMP is synthesized from ATP by adenylate cyclase. Adenylate cyclase is located at the cell membranes. Adenylate cyclase is activated by the hormones glucagon and adrenaline and by G protein. Liver adenylate cyclase responds more strongly to glucagon, and muscle adenylate cyclase responds more strongly to adrenaline. cAMP decomposition into AMP is catalyzed by the enzyme phosphodiesterase.60-92-4C00575607617489CAMP5851DB02527NC1=NC=NC2=C1N=CN2[C@@H]1O[C@@H]2COP(O)(=O)O[C@H]2[C@H]1OC10H12N5O6PInChI=1S/C10H12N5O6P/c11-8-5-9(13-2-12-8)15(3-14-5)10-6(16)7-4(20-10)1-19-22(17,18)21-7/h2-4,6-7,10,16H,1H2,(H,17,18)(H2,11,12,13)/t4-,6-,7-,10-/m1/s1IVOMOUWHDPKRLL-KQYNXXCUSA-N(4aR,6R,7R,7aS)-6-(6-amino-9H-purin-9-yl)-2,7-dihydroxy-hexahydro-2lambda5-furo[3,2-d][1,3,2]dioxaphosphinin-2-one329.2059329.052519653-1.963(4aR,6R,7R,7aS)-6-(6-aminopurin-9-yl)-2,7-dihydroxy-tetrahydro-4H-2lambda5-furo[3,2-d][1,3,2]dioxaphosphinin-2-one0-1FDB001497Cyclic AMP;3'5'-cyclic amp;6-(6-amino-9h-purin-9-yl)tetrahydro-4h-furo[3,2-d][1,3,2]dioxaphosphinine-2,7-diol 2-oxide;Acrasin;Adenosine 3',5'-cyclic monophosphate;Adenosine 3',5'-cyclic phosphate;Adenosine 3',5'-cyclophosphate;Adenosine 3',5'-monophosphate;Adenosine 3,5'-cyclic monophosphorate;Adenosine 3,5'-cyclic monophosphoric acid;Adenosine cyclic monophosphate;Adenosine cyclic-monophosphate;Adenosine-cyclic-phosphate;Adenosine-cyclic-phosphoric-acid;Cyclic 3',5'-amp;Cyclic 3',5'-adenylate;Cyclic 3',5'-adenylic acid;Cyclic amp;Cyclic adenosine 3',5'-phosphate;Camp;Adenosine 3',5'-phosphate;Adenosine-3',5'-cyclic-monophosphate;Cyclic adenylic acid;Adenosine 3',5'-cyclic monophosphoric acid;Adenosine 3',5'-cyclic phosphoric acid;Adenosine 3',5'-phosphoric acid;Adenosine-3',5'-cyclic-monophosphoric acid;Cyclic adenylatePW_C000041cAMP2671647529353910002119168417414118301987870911180044184121904122124457135423MagnesiumHMDB0000547Magnesium salts are essential in nutrition, being required for the activity of many enzymes, especially those concerned with oxidative phosphorylation. Physiologically, it exists as an ion in the body. It is a component of both intra- and extracellular fluids and is excreted in the urine and feces. Deficiency causes irritability of the nervous system with tetany, vasodilatation, convulsions, tremors, depression, and psychotic behavior. Magnesium ion in large amounts is an ionic laxative, and magnesium sulfate (Epsom salts) is sometimes used for this purpose. So-called "milk of magnesia" is a water suspension of one of the few insoluble magnesium compounds, magnesium hydroxide; the undissolved particles give rise to its appearance and name. Milk of magnesia is a mild base, and is commonly used as an antacid.22537-22-0C003058881842013-HYDROXY-MAGNESIUM-PROTOPORP865DB01378[Mg++]MgInChI=1S/Mg/q+2JLVVSXFLKOJNIY-UHFFFAOYSA-Nmagnesium(2+) ion24.30523.9850418980magnesium(2+) ion22FDB003518Magnesium;Magnesium ions;Magnesium ion;Magnesium, doubly charged positive ion;Magnesium, ion (mg(2+));Mg(2+);Mg2+PW_C000423Mg2+86822742681647627272681158191888322936399833992211167461483491529431764142124102411592942233126293373745403147749148695449745652531045329111535611253761035906147593415160381556094161625016664841786594164688116069791997170205719420672272137233211725021473102167313198747322211763132118432101231222512324249125132881258122612729290152752851533730877137133772363297793733678393334784173357848911578522331785363567857413080020368800451848004837280623118806541358086515809652538184151938323839490027108596223110559390115687398119974406120070122120247382120702407120981408121181124121265429121319419121924125122086405122408422122759120122921399123307119123546374123835464123889455124477136124637376124978375125447297125598484125669479125777481125921482125947299125973495126000490126243478126553491126753300127125389127164501127380502127407388127451507127804209128125508128347395986Guanosine triphosphateHMDB0001273Guanosine triphosphate (GTP) is a guanine nucleotide containing three phosphate groups esterified to the sugar moiety. GTP functions as a carrier of phosphates and pyrophosphates involved in channeling chemical energy into specific biosynthetic pathways. GTP activates the signal transducing G proteins which are involved in various cellular processes including proliferation, differentiation, and activation of several intracellular kinase cascades. Proliferation and apoptosis are regulated in part by the hydrolysis of GTP by small GTPases Ras and Rho. Another type of small GTPase, Rab, plays a role in the docking and fusion of vesicles and may also be involved in vesicle formation. In addition to its role in signal transduction, GTP also serves as an energy-rich precursor of mononucleotide units in the enzymatic biosynthesis of DNA and RNA.86-01-1C00044683015996GTP6569NC1=NC2=C(N=CN2[C@@H]2O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]2O)C(=O)N1C10H16N5O14P3InChI=1S/C10H16N5O14P3/c11-10-13-7-4(8(18)14-10)12-2-15(7)9-6(17)5(16)3(27-9)1-26-31(22,23)29-32(24,25)28-30(19,20)21/h2-3,5-6,9,16-17H,1H2,(H,22,23)(H,24,25)(H2,19,20,21)(H3,11,13,14,18)/t3-,5-,6-,9-/m1/s1XKMLYUALXHKNFT-UUOKFMHZSA-N({[({[(2R,3S,4R,5R)-5-(2-amino-6-oxo-6,9-dihydro-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)phosphonic acid523.1804522.990659781-1.708triphosphate, guanosine0-3FDB0225275'-gtp;Gtg;Gtp;Guanosine 5'-(tetrahydrogen triphosphate);Guanosine 5'-triphosphate;Guanosine 5'-triphosphorate;Guanosine 5'-triphosphoric acid;Guanosine triphosphate;Guanosine mono(tetrahydrogen triphosphate) (ester);H4gtp;Guanosine-5'-triphosphatePW_C000986GTP81824041939240911441537350068553841036043155610316164901787478222117531151176919811981151127252906932717696222577144133775441117795113280025368800883088012116489113253119985406120066122121204124122768120122818135123774118125365479125443297126480299126907501126982205128051388170PyrophosphateHMDB0000250The anion, the salts, and the esters of pyrophosphoric acid are called pyrophosphates. The pyrophosphate anion is abbreviated PPi and is formed by the hydrolysis of ATP into AMP in cells. This hydrolysis is called pyrophosphorolysis. The pyrophosphate anion has the structure P2O74-, and is an acid anhydride of phosphate. It is unstable in aqueous solution and rapidly hydrolyzes into inorganic phosphate. Pyrophosphate is an osteotoxin (arrests bone development) and an arthritogen (promotes arthritis). It is also a metabotoxin (an endogenously produced metabolite that causes adverse health affects at chronically high levels). Chronically high levels of pyrophosphate are associated with hypophosphatasia. Hypophosphatasia (also called deficiency of alkaline phosphatase or phosphoethanolaminuria) is a rare, and sometimes fatal, metabolic bone disease. Hypophosphatasia is associated with a molecular defect in the gene encoding tissue non-specific alkaline phosphatase (TNSALP). TNSALP is an enzyme that is tethered to the outer surface of osteoblasts and chondrocytes. TNSALP hydrolyzes several substances, including inorganic pyrophosphate (PPi) and pyridoxal 5'-phosphate (PLP), a major form of vitamin B6. When TSNALP is low, inorganic pyrophosphate (PPi) accumulates outside of cells and inhibits the formation of hydroxyapatite, one of the main components of bone, causing rickets in infants and children and osteomalacia (soft bones) in adults. Vitamin B6 must be dephosphorylated by TNSALP before it can cross the cell membrane. Vitamin B6 deficiency in the brain impairs synthesis of neurotransmitters which can cause seizures. In some cases, a build-up of calcium pyrophosphate dihydrate crystals in the joints can cause pseudogout.14000-31-8C0001364410218361PPI559142DB04160[O-]P([O-])(=O)OP([O-])([O-])=OO7P2InChI=1S/H4O7P2/c1-8(2,3)7-9(4,5)6/h(H2,1,2,3)(H2,4,5,6)/p-4XPPKVPWEQAFLFU-UHFFFAOYSA-J(phosphonooxy)phosphonic acid173.9433173.9119253784pyrophosphoric acid0-3FDB021918(4-)diphosphoric acid ion;(p2o74-)diphosphate;Diphosphate;Diphosphoric acid;Ppi;Pyrometaphosphate;Pyrophosphate;Pyrophosphate tetraanion;Pyrophosphate(4-) ion;[o3popo3](4-);Diphosphat;P2o7(4-);Pyrophosphat;Pyrophosphate ion;Phosphonato phosphoric acid;Pyrophosphoric acid;Pyrophosphoric acid ionPW_C000170Ppi1223546384292373532882221217316204924105928152941751448685450348952521045294101540911754241035433118545812055481115559132558413356061355655108587910762391666978199707318871341637272160731219873182138275151828321011869161120022221204116412315225123232491251228812579226126952901521930615375183476017425613154269731877235329773171287763533678416335789283317915311279950134799581308004737280417170856301947863849481412594819382986782231106343911132703951132753891155271361155323991199341221200171241200324061203304101209364071212614291213411211214863831224074221229854441235021191238314641240443981249773751253242971253952991254104791255974841256564851258764811265524911268692051269353881269505011273372061281245084885D(1A) dopamine receptorP21728This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclaseHMDBP10808DRD15q35.1BC074979131917341622498714135587599864Adenylate cyclase type 2Q08462This is a membrane-bound, calmodulin-insensitive adenylyl cyclase.
HMDBP00921ADCY25p15.3AB02898314.6.1.138292417314136381741315cAMP-dependent protein kinase catalytic subunit betaP22694Mediates 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 fluxHMDBP01415PRKACB1p36.1AY92736612.7.11.1138372385323419983618GβP62873Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 is a guanine nucleotide-binding protein (G protein) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein- effector interactionHMDBP08398GNB11p36.33BC0058881381224138144157735010855161869324170006308135590599136006608136181661361876651601Guanine nucleotide-binding protein G(s) subunit alpha isoforms shortP63092Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(s) protein is involved in hormonal regulation of adenylate cyclase:it activates the cyclase in response to beta-adrenergic stimuliHMDBP01781GNAS20q13.3M14631138102413914415873501185516281355885993625Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12Q9UBI6Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein- effector interactionHMDBP08405GNG121p31.3AF188181138112413714415673500985787D(1A) dopamine receptor1PW_P00078789248851922cAMP-dependent protein kinase catalytic subunit beta1PW_P0009221047131513744231122Adenylate cyclase type 21PW_P000122140864157423246524121Guanine nucleotide-binding protein alpha1PW_P00012113916011464201970falsePW_R001970Right7152411Compoundfalse7153411Compoundfalse71549221ProteinComplexfalse18169222.7.11.11596falsePW_R000596Right25164141Compoundfalse2517411Compoundfalse42001701Compoundtrue801224.6.1.11994121207PW_T000207242521Compound152Right1737872013-09-16T11:49:41-06:002013-09-16T11:49:41-06:0014837452153false51522010regular10010083755223true10010010regular100100838993653false41560010regular50308394414281false201068010regular200190839541281false260568010regular200190840241281false2895121010regular200190840342329false2400117010regular10025840442329false2760105510regular100251137052153false98042510regular100100113715223true10010010regular1001001137898654false90076010regular50301137993653false90064510regular50301138098654false166074010regular50301138193653false128077510regular503011382170143false248068010regular10010011383423149false234250010regular100251138498654false218552510regular50304316488580false4604758subunitregular20013043518642false18605158subunitregular150704352131522false244011858subunitregular150704353131522false263010308subunitregular150705959488580false9555058subunitregular2001305972361898false5655958subunitregular15070597316011497false4355958subunitregular1507059743625142false5056558subunitregular15070597516011497false9206208subunitregular150705976361898false10506208subunitregular1507059773625142false10056708subunitregular150705978488580false12504958subunitregular2001305979361898false3259808subunitregular1507059803625142false3259258subunitregular15070598116011497false16757458subunitregular150705982864142false23125158subunitregular15070598316011497false22025258subunitregular1507035827873404294431636059223402432943521567840312761Cofactor36069223402433043531568840412763Cofactor4910787340593059594920122340145943598223421138317779Cofactor4921121340145944598312711M565 320 C565 364 564 457 565 500 83false18trueM 427.20000707617737 362.18750178972437 L 435 375 L 442.19595247413 361.8387588734929false12712M111 112 C134 128 174 155 198 172 5true1812757M1825 780 C1890 743 1964 697 2046 614 C2104 545 2105 488 2277 525 83false18trueM 1670.0004720509992 410.119001290498 L 1685 410 L 1677.3971778848452 397.0695283966395falsefalsefalse12758M2277 525 C2066 422 1935 486 1935 515 83false18trueM 1770.018399017441 415.74271932746143 L 1785 415 L 1776.8659857032571 402.39691262347264false12759M2705 870 C2705 900 2705 1000 2705 1030 83false1812760M2895 1305 C2759 1298 2705 1130 2705 1100 83false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false12761M2490 1225 L2490 1275 L2540 1225 z10true1812762M2590 1220 C2689 1236 2705 1130 2705 1100 83false1812763M2275 1050 L2275 1100 L2325 1050 z10true1812765M2515 1255 C2516 1278 2442 1358 2442 1390 83false18trueM 1920.3427211552848 1261.5582501740396 L 1927 1275 L 1935.3122573982391 1262.5137524874197false17750M696 683 C736 684 845 683 899 683 83false18trueM 720.0644009829867 408.6115180941069 L 735 410 L 728.7346610946918 396.37115087758207false17751M111 112 C134 128 174 155 198 172 5true1817769M925 675 C940 708 946 724 925 760 5false18trueM 839.9468550441649 556.261556296296 L 825 555 L 831.3808877211858 568.5751343230784false17772M1080 670 C1307 682 1058 1039 475 1015 5false18trueM 1562.3134879461163 688.0032750737846 L 1575 680 L 1561.725704445686 673.0147958128115false17773M1080 670 C1136 680 1572 790 1675 780 5false18trueM 1560.0644009829866 678.6115180941069 L 1575 680 L 1568.7346610946918 666.3711508775821false17774M1155 575 C1178 599 1246 611 1290 565 5false18trueM 1176.4405683624252 479.57156293667333 L 1180 465 L 1165.6009405052098 469.20322324716284false17775M1080 670 C1234 699 1281 758 1305 775 5false18trueM 1150.0644009829866 663.6115180941069 L 1165 665 L 1158.7346610946918 651.3711508775821false17776M2110 680 C2122 620 2171 558 2202 560 5false1817777M2705 680 C2682 560 2438 533 2462 550 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false17778M2530 680 C2516 588 2438 533 2462 550 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false17779M250 250 L250 300 L300 250 z10true182501340197028087839512759Left8088840212760Right342360512762Right25481816360632683405961410779839417776Left10780839517777Right107811138217778Right3440804920344119944921323207340729837412711Left730837512712Right20835821734212073409091137017750Left9101137117751Right2744910173753671340217false2367139016regular435360512765Left338389651137866113796711380681138169113847712757781275818517769186177721871777318817774189177751643512359722459732559742659752759762859772959783059793159803259815758917251300.60.6021650040018743812709361.01.00290484497577M345 650 C345 600 395 550 445 550 C1257 550 2314 550 3126 550 C3176 550 3226 600 3226 650 C3226 886 3226 1192 3226 1428 C3226 1478 3176 1528 3126 1528 C2314 1528 1257 1528 445 1528 C395 1528 345 1478 345 1428 C345 1192 345 886 345 650 1true62881.0978.049515Regulatory Subunit27951175201.01.01601549615Regulatory Subunit24901000201.01.01601549715Activation23751275201.01.01601549815Activation2040465201.01.01601549915Activation480365201.01.01601550015Activation2640915201.01.01601550115Intracellular Space415820201.01.01601550215Extracellular Space105825201.01.0160152911825230281405325815594429771154