366PathwayIntracellular Signalling Through LHCGR Receptor and Luteinizing Hormone/ChoriogonadotropinThe luteinizing hormone/choriogonadotropin receptor (LHCGR) is a transmembrane G protein-coupled receptor located most prominently in the ovary and testis but also found in organs such as the uterus, breasts, prostate, and seminal vesicles. As its name suggests, the receptor is activated by both luteinizing hormone (LH) and chorionic gonadotropins (e.g. hCG) and plays an important role in the regulation of reproduction. In the ovaries, activation of LHCGR by follicle-stimulating hormone (FSH) leads to follicular maturation and ovulation. In the testis, LHCGR activation is essential for testosterone production and spermatogenesis. The LHCGR receptor activates G(s) proteins which leads to the activation of adenylyl cyclase and produces the secondary messenger cAMP. cAMP then activates protein kinase A (PKA) which phosphorylates downstream effectors that lead to a specific cellular response. Specifically, LHCGR upregulates the mitochondrial enzyme P450scc (cholesterol side-chain cleavage enzyme) which increases the production of steroid hormones such as testosterone and estrogen.ProteinPW000450TopPathwayVisualizationContext46622503000#000099PathwayVisualization350366Intracellular Signalling Through LHCGR Receptor and Luteinizing Hormone/ChoriogonadotropinThe luteinizing hormone/choriogonadotropin receptor (LHCGR) is a transmembrane G protein-coupled receptor located most prominently in the ovary and testis but also found in organs such as the uterus, breasts, prostate, and seminal vesicles. As its name suggests, the receptor is activated by both luteinizing hormone (LH) and chorionic gonadotropins (e.g. hCG) and plays an important role in the regulation of reproduction. In the ovaries, activation of LHCGR by follicle-stimulating hormone (FSH) leads to follicular maturation and ovulation. In the testis, LHCGR activation is essential for testosterone production and spermatogenesis. The LHCGR receptor activates G(s) proteins which leads to the activation of adenylyl cyclase and produces the secondary messenger cAMP. cAMP then activates protein kinase A (PKA) which phosphorylates downstream effectors that lead to a specific cellular response. Specifically, LHCGR upregulates the mitochondrial enzyme P450scc (cholesterol side-chain cleavage enzyme) which increases the production of steroid hormones such as testosterone and estrogen.Protein1689Follicular Maturation and OvulationSubPathway114141Compound2690Testosterone Production and Support spematogenesisSubPathway114241Compound211037719343Kremer H, Kraaij R, Toledo SP, Post M, Fridman JB, Hayashida CY, van Reen M, Milgrom E, Ropers HH, Mariman E, et al.: Male pseudohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene. Nat Genet. 1995 Feb;9(2):160-4. doi: 10.1038/ng0295-160.366Pathway1104Krauss, G. Biochemistry of signal transduction and regulation. (3rd ed.) (2003) Weinheim; New York : Wiley-VCH366Pathway1CellCL:00000003NeuronCL:00005402Platelet CL:00002335HepatocyteCL:00001824CardiomyocyteCL:00007468Beta cellCL:00006397Epithelial CellCL:000006621Theca CellCL:000050322Granulosa CellCL:000050120Leydig CellCL:000017814Parietal CellCL:000016219Sertoli CellCL:00002166MyocyteCL:00001871Homo sapiens9606EukaryoteHuman3Escherichia coli562Prokaryote24Solanum lycopersicum4081EukaryoteTomato18Saccharomyces cerevisiae4932EukaryoteYeast21Xenopus laevis8355EukaryoteAfrican clawed frog4Arabidopsis thaliana3702EukaryoteThale cress12Mus musculus10090EukaryoteMouse49Bathymodiolus platifrons220390EukaryoteDeep sea mussel60Nitzschia sp.0001EukaryoteNitzschia45Bos taurus9913EukaryoteCattle17Rattus norvegicus10116EukaryoteRat10Drosophila melanogaster7227EukaryoteFruit fly6Caenorhabditis elegans6239EukaryoteRoundworm2Bacteria2ProkaryoteBacteria19Schizosaccharomyces pombe4896Eukaryote25Escherichia coli (strain K12)83333Prokaryote23Pseudomonas aeruginosa287Prokaryote51Picea sitchensis3332EukaryoteSitka spruce29Saccharomyces cerevisiae (strain ATCC 204508 / S288c)559292EukaryoteBaker's yeast56Andro6666Eukaryote157Acinetobacter baumannii 107673Prokaryote5CytoplasmGO:00057373Mitochondrial MatrixGO:00057591CytosolGO:000582910Cell MembraneGO:000588635ChloroplastGO:000950714Mitochondrial Outer MembraneGO:00057412MitochondrionGO:000573915NucleusGO:00056344PeroxisomeGO:000577713Endoplasmic ReticulumGO:00057837Endoplasmic Reticulum MembraneGO:000578927Peroxisome MembraneGO:000577831Periplasmic SpaceGO:000562011Extracellular SpaceGO:000561512Mitochondrial Inner MembraneGO:000574332Inner MembraneGO:007025825Golgi ApparatusGO:000579426Golgi Apparatus MembraneGO:000013919Sarcoplasmic ReticulumGO:001652934Plant-Type VacuoleGO:000032537Basolateral cell membraneGO:001632365Presynaptic membraneGO:004273424BrainBTO:000014289162Endothelium BTO:00003931LiverBTO:00007597297Nervous SystemBTO:000148418PancreasBTO:000098825IntestineBTO:00006488Blood VesselBTO:000110274115cardiocyteBTO:000153935OvaryBTO:000097534TestisBTO:000136328StomachBTO:00013071552632Adrenal CortexBTO:00000459MuscleBTO:00008871411826LungBTO:000076338Myenteric PlexusBTO:00024366KidneyBTO:000067171814EyeBTO:00004391532411HeartBTO:000056273104Adrenal MedullaBTO:00000497188511PW_BS0000084311PW_BS0000042111PW_BS00000214101PW_BS000014731013PW_BS00007385241011PW_BS000085103331PW_BS0001031553241PW_BS0001551613181PW_BS0001611783211PW_BS000178222341PW_BS0000241151012PW_BS0001151985181PW_BS000024151141PW_BS0001512905491PW_BS00002411PW_BS0000012253541PW_BS0000241333121PW_BS0001331115121PW_BS0001111321121PW_BS0001323683601PW_BS0000283081011PW_BS0000241644PW_BS000164253541PW_BS000024406351PW_BS000115122551PW_BS000122124151PW_BS0001241203171PW_BS0001201355171PW_BS0001351181171PW_BS0001184793101PW_BS0001152975101PW_BS0000242991101PW_BS000024501361PW_BS000115205561PW_BS000024388161PW_BS0001122111018PW_BS000024405105PW_BS0001153761017PW_BS00005316212PW_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_BS0000242771218PW_BS00002417018PW_BS0001702811251PW_BS0000242851041PW_BS000024226441PW_BS0000242231241PW_BS000024315123PW_BS0000243221231PW_BS0000243183123PW_BS00002413412121PW_BS00013432914121PW_BS0000283331212PW_BS0000283361121PW_BS00002833217121PW_BS000028350114121PW_BS00002812815121PW_BS0001283511512PW_BS00002835325127PW_BS00002833527121PW_BS00002813013121PW_BS0001303317121PW_BS0000283344121PW_BS000028184121PW_BS0000241192171PW_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_BS0001154812101PW_BS00011548414101PW_BS00011548515101PW_BS00011530013101PW_BS0000244957101PW_BS0001154781010PW_BS00011549127101PW_BS0001154991510PW_BS0001153891461PW_BS0001125161561PW_BS0001153951361PW_BS000113390761PW_BS000112209106PW_BS0000245082761PW_BS000115517156PW_BS0001158911421PW_BS000552215114PW_BS0000212491341PW_BS0000242881441PW_BS00002430635511PW_BS000024171211PW_BS000017372102PW_BS0000283841251PW_BS0001003911261PW_BS00011212112171PW_BS000121432511PW_BS000043562611PW_BS00005621425181PW_BS00002435625121PW_BS00002815111PW_BS0000154192551PW_BS00011545525171PW_BS0001154824101PW_BS00011549025101PW_BS000115502461PW_BS0001155072561PW_BS000115471914PW_BS0000476131PW_BS00000621217181PW_BS0000242273441PW_BS000024241529PW_BS00002425715291PW_BS00002430412PW_BS00002429341PW_BS00002429817101PW_BS0000245131761PW_BS00011594835121PW_BS00056394935122PW_BS00056394734120PW_BS000563599856PW_BS0005017772837114PW_BS00052148113PW_BS000048658285114PW_BS000508898283715714PW_BS00055289928515714PW_BS00055294634119PW_BS00056378924113PW_BS000524113881016PW_BS000581122432111PW_BS000588122632151PW_BS0005881230321171PW_BS0005881234321121PW_BS000588608321PW_BS0005016651818PW_BS0005085602410171PW_BS000204787241013PW_BS000524509516PW_BS0000505291016PW_BS0000527413PW_BS0000741033246513PW_BS000577183261011PW_BS000024107338113PW_BS00057879271PW_BS00052767181018PW_BS0000678346111PW_BS000549105014516PW_BS000577101111114PW_BS0005771014111014PW_BS00057710569116PW_BS000578204111PW_BS0000202441011PW_BS000024986Guanosine 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_C000986GTP81824041939240911441537350068553841036043155610316164901787478222117531151176919811981151127252906932717696222577144133775441117795113280025368800883088012116489113253119985406120066122121204124122768120122818135123774118125365479125443297126480299126907501126982205128051388936Guanosine 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_C000414ATP9221460826616414224781373332799593439976321051821121021464921561421605824055924342727264628122930296631637236166136175143992344743147689148645450328950352651557520597521510052501045291101531311153461125390103540611754301185443120554212955561325569133560313556211085846143585414658761075897147592415160481556109161623016664931786839188687016069761997157205718420672092107225213722921172981987302216739021774082187432163748122274991908186225118472771190317012010281120391641217828512578226126912901326422315327308423263154262132242694318770282537721813477233329774683337763233678037332780413507816812878214351782403537841133578494115788501307886533178919334800283688004618480674119856291948261241132349411328238811628010911991412211999240612015440712024538212036241212124642912139212312139743312147140812197441012206512512207938312208340512240242212244443512291939912300944612381646412395144712395646812402937412452744412461613612463039812463437612494347212497237512501147012530429712537147912539229912551548112559548412612348512622030012623449512624047812654749112659649912691350112712338912773151612778139512779639012780120912811950812816751714077089141cAMPHMDB0000058cAMP 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.60-92-4C00575607617489CAMP5851DB02527[H][C@@]12COP(O)(=O)O[C@@]1([H])[C@@H](O)[C@@H](O2)N1C=NC2=C1N=CN=C2NC10H12N5O6PInChI=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_C000041cAMP2671647529353910002119168417414118301987870911180044184121904122124457135170PyrophosphateHMDB0000250The 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.14000-31-8C0001364410218361PPI559142DB04160OP(O)(=O)OP(O)(O)=OH4O7P2InChI=1S/H4O7P2/c1-8(2,3)7-9(4,5)6/h(H2,1,2,3)(H2,4,5,6)XPPKVPWEQAFLFU-UHFFFAOYSA-N(phosphonooxy)phosphonic acid177.9751177.9432255064pyrophosphoric 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_C000170Ppi122354638429237353288222121731620492410592815294175144868545034895252104529410154091175424103543311854581205548111555913255841335606135565510858791076239166697819970731887134163727216073121987318213827515182832101186916112002222120411641231522512323249125122881257922612695290152193061537518347601742561315426973187723532977317128776353367841633578928331791531127995013479958130800473728041717085630194786384948141259481938298678223110634391113270395113275389115527136115532399119934122120017124120032406120330410120936407121261429121341121121486383122407422122985444123502119123831464124044398124977375125324297125395299125410479125597484125656485125876481126552491126869205126935388126950501127337206128124508140772891423MagnesiumHMDB0000547Magnesium 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+868227426816476272726811581918883229363998339922111674614834915294317641421241024115929422331262933737454031477491486954497456525310453291115356112537610359061475934151603815560941616250166648417865941646881160697919971702057194206722721372332117250214731021673131987473222117631321184321012312225123242491251328812581226127292901527528515337308771371337723632977937336783933347841733578489115785223317853635678574130800203688004518480048372806231188065413580865158096525381841519383238394900271085962231105593901156873981199744061200701221202473821207024071209814081211811241212654291213194191219241251220864051224084221227591201229213991233071191235463741238354641238894551244771361246373761249783751254472971255984841256694791257774811259214821259472991259734951260004901262434781265534911267533001271253891271645011273805021274073881274515071278042091281255081283473951407738911104PhosphateHMDB0001429Phosphate 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-85871032OP(O)(O)=OH3O4PInChI=1S/H3O4P/c1-5(2,3)4/h(H3,1,2,3,4)NBIIXXVUZAFLBC-UHFFFAOYSA-Nphosphoric acid97.995297.9768950963phosphoric 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_C001104Pi24484881458181883129803176314176749250010272947273746312929316672363661385123424922447531503127515875207975216100531711153511125381103544712055431295573133560513556251085693658481435855146591114759411516040155610016162941076487178669110167141176842188688916071612057189206721221173061987389210740221274361637475222819622582582271011824110134257117481321176111511773213119041701192716412014281127282901326322334819174225530442350315424353184369232277018253771942937721713477940336779661307804833278057329782453537866933180022368892793089383138394796384110558390110640391113235941158453981162061091199824061200691221206994071210571241212161251212684291213521211214091231214233821218524051233041191236211181237861361238384641239684471239813991244053761249484721253624791254462971257744811259542991262214781265943001266042981267234841269045011274133881277832091281663951281775131283153895776Glycoprotein hormones alpha chainP012151419015419228076623141476948141481949141907515778Lutropin subunit betaP01229LHB141941541952807652380947217141470511414719471414759481813Lutropin-choriogonadotropic hormone receptorP22888Receptor for lutropin-choriogonadotropic hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclaseHMDBP02152LHCGR2p21X847581419728510141414789481414799471601Guanine 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 stimuliHMDBP01781GNAS20q13.3M1463113810241391441587350118551628135588599139731777139935431399874814036365814089089814089389914148394914148794614322978914330611381441767214434112241443481226144359123014437012343625Guanine 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 interactionHMDBP08405GNG121p31.3AF18818113811241371441567350098513973377714036165814089289814089589914148594914148994614434212241443491226144360123014437112343618GβP62873Guanine 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 interactionHMDBP08398GNB11p36.33BC005888138122413814415773501085516186932417000630813559059913600660813618166136187665138502560139732777140362658140534787140891898140894899141375501414235214148494914148894614250374142960103314330711381443431224144350122614436112301443721234864Adenylate cyclase type 2Q08462This is a membrane-bound, calmodulin-insensitive adenylyl cyclase.
HMDBP00921ADCY25p15.3AB02898314.6.1.13829241731413638174139735777139845481405377891406011831408998981414959481429831073143085787144285814433812241443561226144367123014437812341315cAMP-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 fluxHMDBP01415PRKACB1p36.1AY92736612.7.11.1138372385323419981397207921398914814097331415049481415219491415377891415569471415629461416422614192065814194067141947661422008341427851050142814101114282310141441837214433912241443511226144362123014437312345766Ethylene-responsive transcription factor ESR1Q9SAD4ESR11385223419821802Cyclic AMP-responsive element-binding protein 1P16220This protein binds the cAMP response element (CRE), a sequence present in many viral and cellular promoters. CREB stimulates transcription on binding to the CRE. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. Implicated in synchronization of circadian rhythmicityHMDBP02133CREB12q34X5554513857239802311597427141623263900Serine/threonine-protein phosphatase PP1-alpha catalytic subunitP62136Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development.
HMDBP08684PPP1CA11q13J0475913.1.3.163854233858280267814302010563627Guanine nucleotide-binding protein G(T) subunit gamma-T1P63211Guanine 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 interactionHMDBP08407GNGT17q21.3BC029367151608135589599136222141397347771000Glycoprotein hormones alpha chain1PW_P0010001140577611001Lutropin subunit beta1PW_P0010011142577811002Lutropin-choriogonadotropic hormone receptor1PW_P001002114318131121Guanine nucleotide-binding protein alpha1PW_P0001211391601146420120Guanine nucleotide-binding protein gamma-beta1PW_P000120137362711383618146324115Guanine nucleotide-binding protein alpha-beta-gamma1PW_P000115130160111313627113236181454245520122Adenylate cyclase type 21PW_P000122140864157423246524922cAMP-dependent protein kinase catalytic subunit beta1PW_P0009221047131513744231923Ethylene-responsive transcription factor ESR11PW_P000923104857661925Cyclic AMP-responsive element-binding protein 11PW_P000925105018021924Serine/threonine-protein phosphatase PP1-alpha catalytic subunit1PW_P0009241049390012130falsePW_R002130Right757810021ProteinComplexfalse75799861Compoundfalse75801211ProteinComplexfalse758110021ProteinComplexfalse75829361Compoundfalse75831201ProteinComplexfalse1993115596falsePW_R000596Right25164141Compoundfalse2517411Compoundfalse42001701Compoundtrue801224.6.1.119941211958PW_R001958Right71211211ProteinComplexfalse71221221ProteinComplexfalse71231211ProteinComplexfalse71241221ProteinComplexfalse1970falsePW_R001970Right7152411Compoundfalse7153411Compoundfalse71549221ProteinComplexfalse18169222.7.11.111990falsePW_R001990Right71939231ProteinComplexfalse71949231ProteinComplexfalse719511041Compoundtrue18349222.7.11.112000falsePW_R002000Right72169251ProteinComplexfalse72179251ProteinComplexfalse721811041Compoundtrue18459222.7.11.111996falsePW_R001996Right72069231ProteinComplexfalse720711041Compoundtrue72089231ProteinComplexfalse18419243.1.3.161999falsePW_R001999Right72139251ProteinComplexfalse721411041Compoundtrue72159251ProteinComplexfalse18449243.1.3.16212PW_T00021224710001ProteinComplex152Right24810011ProteinComplex152Right17710022013-09-17T12:28:36-06:002013-09-17T12:28:36-06:00148581986254false63566010regular50308582936253false101563010regular5030858398629false129559510regular10035858493653false65549510regular50308585414242false165554010regular5030858641281false218558510regular2001908587170245false207356810regular6343858842329false190038510regular100258589986254false174539510regular5030859042329false148039519regular10025859141281false2415112510regular200190859242329false2095117010regular10025859342329false224096019regular1002585941104246false1563153010regular444385951104246false1343153510regular44431152693653false24049510regular503045815776152false7053258subunitregular150704582577622true4154558subunitregular1507045835778152false7052608subunitregular150704584577822true4954558subunitregular15070458518131480false6653758subunitregular20013045971601298false12706258subunitregular1507045981813280false11003708subunitregular20013045993625297false1009408subunitregular150704600361822false1008758subunitregular1507046011601298false6754908subunitregular1507046023625297false7455508subunitregular150704603361822false8154908subunitregular150704604864299false18754008subunitregular1507046051601298false17604008subunitregular150704606864299false14554058subunitregular150704607131526false206011808subunitregular160804608131526false22059708subunitregular160804609576622false139512408subunitregular150704610576622false151015658subunitregular150704611180222false139513508subunitregular150704612180222false129015608subunitregular150704613390022false74211658subunitregular1507060655776152false3251708subunitregular150706066577622true-502908subunitregular1507060675778152false3251058subunitregular150706068577822true302908subunitregular15070606918131480false2953858subunitregular200130607016011498false2554958subunitregular15070607136182false4004958subunitregular15070607236251497false3255558subunitregular150703783100035015455845813784100035024559458237851001350154560458337861001350245614584378710023504562458537961213502457445971632858313168Cofactor379710023502457545983798120350245764599457746003799115350245784601457946024580460338001223502458146041633858813175Cofactor38011213502458246051634858913176Cofactor38021223502458346061635859013180Cofactor38039223502458446071636859213184Cofactor38049223502458546081637859313186Cofactor380592335024586460938069233502458746103807925350245884611380892535024589461238099243502459046134967100035015599660654968100035025997606649691001350155998606749701001350259996068497110023506000606913150M512 582 C535 582 632 583 675 583 149false18trueM 482.5 372.0096189432334 L 490 385 L 497.5 372.0096189432334false13151M490 455 C490 425 790 520 790 490 5true1813152M780 330 C780 360 770 370 770 400 5true1813153M570 455 C570 425 790 520 790 490 5true1813165M660 660 C688 630 719 588 680 525 5false18trueM 743.2145356150122 532.0976086451407 L 730 525 L 730.4605584146942 539.992927864385false13166M1040 630 C1040 586 850 550 820 550 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false13167M865 445 C895 445 785 525 815 525 5true1813168M935 710 L935 760 L985 710 z10true1813169M1270 660 C1131 661 1110 572 820 550 5false18trueM 1107.0096189432334 597.5 L 1120 590 L 1107.0096189432334 582.5false13170M1140 440 C1058 522 888 480 865 445 5false18trueM 835.7946268841059 468.83554477691416 L 830 455 L 820.9153801900482 466.9360664755451false13171M250 975 C606 985 1298 630 820 550 5false18trueM 1105.1924390042777 501.0051891007868 L 1095 490 L 1090.565446167406 504.32950565462136false13172M1680 540 C1679 481 1713 435 1760 435 5false1813173M2285 585 C2283 491 2136 435 2025 435 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false13174M2104.5 568 C2101.5 502 2097 436 2025 435 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false13175M275 280 L275 330 L325 280 z10true1813176M275 435 L275 485 L325 435 z10true1813177M1420 660 C1450 660 1685 269 1835 400 149false1813178M1835 400 C1784 354 1657 299 1530 405 149false18trueM 1517.9903810567666 407.5 L 1505 415 L 1517.9903810567666 422.5false13179M1760 435 C1730 435 1473.5 438 1497.5 455 5true1813180M100 150 L100 200 L150 150 z10true1813181M1455 440 C1425 440 1473.5 438 1497.5 455 5true1813182M2285 775 C2285 805 2285 940 2285 970 149false18falsefalse13183M2415 1220 C2299 1219 2285 1080 2285 1050 149false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false13184M100 150 L100 200 L150 150 z10true1813185M2220 1220 C2271 1220 2285 1080 2285 1050 149false18trueM 1902.7418178388511 1177.0850724474867 L 1890 1185 L 1903.2254372490156 1192.0772741625822false13186M100 150 L100 200 L150 150 z10true1813187M2385 680 C2557 682 2467 563 2650 560 5false18trueM 2242.0096189432334 582.5 L 2255 575 L 2242.0096189432334 567.5false13188M2385 680 C2415 680 2620 680 2650 680 5false18trueM 2312.0096189432334 712.5 L 2325 705 L 2312.0096189432334 697.5false13189M1563 1551.5 C1533 1551.5 1870 1185 1840 1185 5true18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false13190M1545 1275 C1578 1273 2012 1223 2060 1220 5false1813191M1660 1600 C1711 1554 2003 1276 2060 1220 5false18trueM 1463.2648480723726 1422.4823210481895 L 1455 1435 L 1469.973052004872 1435.8987289131883false13192M1343 1556.5 C1313 1556.5 1870 1185 1840 1185 5true18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false13193M1545 1385 C1685 1354 2070 1273 2140 1260 5false1813194M1440 1595 C1628 1507 2020 1315 2140 1260 5false18trueM 1483.065138803188 1697.3527261401791 L 1475 1710 L 1489.9854298528178 1710.6609781586978false13195M1607 1551.5 C1637 1551.5 712 1200 742 1200 5true1813196M1395 1275 C1236 1244 990 1213 892 1200 5false18trueM 1297.1804171038148 1282.7883434931848 L 1310 1275 L 1296.84530523341 1267.7920872925756false13197M1510 1600 C1480 1576 968.5 1249 892 1200 5false1813198M1387 1556.5 C1417 1556.5 712 1200 742 1200 5true1813199M1395 1385 C1222 1325 885 1238 817 1235 5false18trueM 1317.9903810567666 1577.5 L 1305 1585 L 1317.9903810567666 1592.5false13200M1290 1595 C1244 1560 904 1305 817 1235 5false1817948M400 240 C400 270 400 380 400 410 149false18trueM 452.5 372.0096189432334 L 460 385 L 467.5 372.0096189432334false17949M25 290 C25 260 420 530 420 500 5true1817950M400 175 C400 205 400 380 400 410 5true1817951M105 290 C105 260 420 530 420 500 5true182564350213028193858113165Left8194858213166Right504378713167Left505379613169Right506379713170Right507379813171Right259719933799256535059628195858513172Left8196858613173Right8197858713174Right2598803800259919943801256635019582508379613177Left509380013178Left510380113179Right511380213181Right2567350197028198858613182Left8199859113183Right512380313185Right2600181638042568350199028200859413189Right513380513190Left514380613191Right2601183438032569350200028201859513192Right515380713193Left516380813194Right2602184538032570350199628202859413195Left517380513196Left518380613197Right2603184138092571350199928203859513198Left519380713199Left520380813200Right26041844380933521235023378313150Left24378413151Right25378513152Left26378613153Right218378717743921235055496717948Left56496817949Right57496917950Left58497017951Right2884971177768689350217false265052516regular725858613187Left769690350217false265064516regular726858613188Left3985848311526636070646071656072185769116614610.20.2065430001764483744195010511.01.0-1552149024048374527713352.22.2031432726748374642016241.61.6-13023280360585M127 525 C127 475 177 425 227 425 C999 425 2003 425 2775 425 C2825 425 2875 475 2875 525 C2875 979 2875 1569 2875 2023 C2875 2073 2825 2123 2775 2123 C2003 2123 999 2123 227 2123 C177 2123 127 2073 127 2023 C127 1569 127 979 127 525 1true62748.01698.0476297M1027 1175 C1027 1125 1077 1075 1127 1075 C1336 1075 1609 1075 1818 1075 C1868 1075 1918 1125 1918 1175 C1918 1388 1918 1665 1918 1878 C1918 1928 1868 1978 1818 1978 C1609 1978 1336 1978 1127 1978 C1077 1978 1027 1928 1027 1878 C1027 1665 1027 1388 1027 1175 93true6891.0903.0476298M1125 1277 C1125 1227 1175 1177 1225 1177 C1376 1177 1572 1177 1723 1177 C1773 1177 1823 1227 1823 1277 C1823 1428 1823 1623 1823 1774 C1823 1824 1773 1874 1723 1874 C1572 1874 1376 1874 1225 1874 C1175 1874 1125 1824 1125 1774 C1125 1623 1125 1428 1125 1277 93true6698.0697.0527235Regulatory Subunit2345985201.01.020015528235Regulatory Subunit25451090201.01.020015531235Regulatory Subunit7501110201.01.020015532235Activation1570250201.31.320015533235Activation295285201.01.020015534235Activation2150815201.31.320015535235Activation2405635201.01.020015449483235Nucleus1261991201.91.920015449924235Transcription13241627201.61.6200152829627621563100210461948200339#FFF9C94946957