14PathwayCorticotropin Activation of Cortisol ProductionCorticotropin, also known as ACTH or adrenocorticotropic hormone, is a peptide tropic hormone synthesized by the anterior pituitary gland in response to the release of corticotropin-releasing hormone (CRH) from the hypothalamus. It is produced from the cleavage of pre-pro-opiomelanocortin by various endopeptidases, along with other physiologically active peptide fragments such as β-lipotropin, γ-lipotropin, melanocyte-stimulating hormone (MSH), and β-endorphin. As an essential component of the hypothalamic-pituitary-adrenal axis, corticotropin is primarily responsible for increasing the adrenal cortex production of cortisol in response to stress. The ACTH receptor activates G(s) proteins which lead to the activation of adenylyl cyclase which produces the secondary messenger cAMP. cAMP activates pKA (protein kinase A) which phosphorylates downstream effectors that lead to androgen and cortisol production.ProteinPW000442TopPathwayVisualizationContext45818574250#000099PathwayVisualization34214Corticotropin Activation of Cortisol ProductionCorticotropin, also known as ACTH or adrenocorticotropic hormone, is a peptide tropic hormone synthesized by the anterior pituitary gland in response to the release of corticotropin-releasing hormone (CRH) from the hypothalamus. It is produced from the cleavage of pre-pro-opiomelanocortin by various endopeptidases, along with other physiologically active peptide fragments such as β-lipotropin, γ-lipotropin, melanocyte-stimulating hormone (MSH), and β-endorphin. As an essential component of the hypothalamic-pituitary-adrenal axis, corticotropin is primarily responsible for increasing the adrenal cortex production of cortisol in response to stress. The ACTH receptor activates G(s) proteins which lead to the activation of adenylyl cyclase which produces the secondary messenger cAMP. cAMP activates pKA (protein kinase A) which phosphorylates downstream effectors that lead to androgen and cortisol production.Protein164890SubPathway1079922ProteinComplex2108045Compound10019175632Naville D, Barjhoux L, Jaillard C, Saez JM, Durand P, Begeot M: Stable expression of normal and mutant human ACTH receptor: study of ACTH binding and coupling to adenylate cyclase. Mol Cell Endocrinol. 1997 Apr 25;129(1):83-90.14Pathway1002Krauss, G. Biochemistry of signal transduction and regulation. (3rd ed.) (2003) Weinheim; New York : Wiley-VCH14Pathway1CellCL:00000003NeuronCL:00005402Platelet CL:00002335HepatocyteCL:00001824CardiomyocyteCL:00007468Beta cellCL:00006397Epithelial CellCL:000006614Parietal CellCL:000016222Granulosa CellCL:000050119Sertoli CellCL:00002166MyocyteCL:000018721Theca CellCL:000050320Leydig CellCL:00001781Homo 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 spruce56Andro6666Eukaryote157Acinetobacter 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:000013937Basolateral cell membraneGO:001632365Presynaptic membraneGO:004273424BrainBTO:000014289162Endothelium BTO:00003931LiverBTO:00007597297Nervous SystemBTO:000148418PancreasBTO:000098825IntestineBTO:00006488Blood VesselBTO:000110274115cardiocyteBTO:000153932Adrenal CortexBTO:000004528StomachBTO:00013071552635OvaryBTO:000097534TestisBTO:00013639MuscleBTO: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_BS0001151225321111PW_BS000588122432111PW_BS0005881229321151PW_BS000588122632151PW_BS000588409115PW_BS0001151223321011PW_BS0005881227321051PW_BS000588599856PW_BS0005017772837114PW_BS00052148113PW_BS000048658285114PW_BS000508898283715714PW_BS00055289928515714PW_BS00055294935122PW_BS00056394634119PW_BS00056378924113PW_BS000524113881016PW_BS000581608321PW_BS0005016651818PW_BS0005085602410171PW_BS000204787241013PW_BS000524509516PW_BS0000505291016PW_BS0000527413PW_BS0000741033246513PW_BS000577183261011PW_BS00002494835121PW_BS000563107338113PW_BS00057879271PW_BS00052794734120PW_BS00056367181018PW_BS0000678346111PW_BS000549105014516PW_BS000577101111114PW_BS0005771014111014PW_BS0005772541111PW_BS0000252441011PW_BS000024204111PW_BS000020986Guanosine 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+8682274268164762727268115819188832293639983399221116746148349152943176414212410241159294223312629337374540314774914869544974565253104532911153561125376103590614759341516038155609416162501666484178659416468811606979199717020571942067227213723321172502147310216731319874732221176313211843210123122251232424912513288125812261272929015275285153373087713713377236329779373367839333478417335784891157852233178536356785741308002036880045184800483728062311880654135808651580965253818415193832383949002710859622311055939011568739811997440612007012212024738212070240712098140812118112412126542912131941912192412512208640512240842212275912012292139912330711912354637412383546412388945512447713612463737612497837512544729712559848412566947912577748112592148212594729912597349512600049012624347812655349112675330012712538912716450112738050212740738812745150712780420912812550812834739514077389145CortisolHMDB0000063Cortisol is the main glucocorticoid secreted by the adrenal cortex and it is involved in the stress response. Its synthetic counterpart hydrocortisone is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. Hydrocortisone is synthesized from pregnenolone and is used as an immunosuppressive drug given by injection in the treatment of severe allergic reactions such as anaphylaxis and angioedema, in place of prednisolone in patients who need steroid treatment but cannot take oral medication, and peri-operatively in patients on long-term steroid treatment to prevent an Addisonian crisis. Cortisol increases blood pressure, blood sugar levels, may cause infertility in women, and suppresses the immune system. The amount of cortisol present in the serum undergoes diurnal variation, with the highest levels present in the early morning and lower levels in the evening, several hours after the onset of sleep. Cortisol is found to be associated with ACTH deficiency and glucocorticoid deficiency, which are inborn errors of metabolism. Cortisol binds to the cytosolic glucocorticoid receptor. After binding the receptor, the newly formed receptor-ligand complex translocates itself into the cell nucleus where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA-bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically, glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes and prevents phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In other words, the two main products of inflammation, prostaglandins and leukotrienes, are inhibited by the action of glucocorticoids. Glucocorticoids also stimulate the escape of lipocortin-1 into the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst, and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines, etc.) from neutrophils, macrophages, and mastocytes. Additionally, the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.50-23-7C007355754176505551DB00741[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12CC21H30O5InChI=1S/C21H30O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h9,14-16,18,22,24,26H,3-8,10-11H2,1-2H3/t14-,15-,16-,18+,19-,20-,21-/m0/s1JYGXADMDTFJGBT-VWUMJDOOSA-N(1S,2R,10S,11S,14R,15S,17S)-14,17-dihydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one362.4599362.20932407-3.263(1S,2R,10S,11S,14R,15S,17S)-14,17-dihydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one00FDB02188811-hydrocortisone;11-beta-hydrocortisone;11-beta-hydroxycortisone;11a-hydroxycorticosterone;11alpha-hydroxycorticosterone;11b,17,21-trihydroxyprogesterone;11b-hydrocortisone;11b-hydroxycortisone;11beta,17,21-trihydroxyprogesterone;11beta-hydrocortisone;11beta-hydroxycortisone;17-hydroxycorticosterone;17a-hydroxycorticosterone;17alpha-hydroxycorticosterone;4-pregnene-11alpha,21-triol 3,20-dione;4-pregnene-11b,17a,21-triol-3,20-dione;Acticort;Aeroseb hc;Aeroseb-hc;Ala-cort;Ala-scalp;Alacort;Algicirtis;Alphaderm;Amberin;Anflam;Anti-inflammatory hormone;Aquacort;Aquanil hc;Barseb hc;Basan-corti;Caldecort spray;Cetacort;Chronocort;Clear aid;Cleiton;Cobadex;Compound f;Cor-tar-quin;Cort-dome;Cort-quin;Cortanal;Cortenema;Cortesal;Corticreme;Cortifan;Cortifoam;Cortiment;Cortisol alcohol;Cortisolonum;Cortisporin;Cortisporin otico;Cortispray;Cortizol;Cortolotion;Cortonema;Cortoxide;Cremesone;Cremicort-h;Cutisol;Delacort;Derm-aid;Dermil;Dermolate;Dihydrocostisone;Dioderm;Dome-cort;Domolene-hc;Drotic;Ef corlin;Efcorbin;Efcortelan;Efcortelin;Eldercort;Epicort;Epiderm h;Esiderm h;Evacort;Ficortril;Fiocortril;Foille insetti;Genacort;Gyno-cortisone;H-cort;Hc;Heb cort;Heb-cort;Hidalone;Hidro-colisona;Hidrocortisona;Hycort;Hycortol;Hycortole;Hydracort;Hydrasson;Hydro-adreson;Hydro-colisona;Hydrocort;Hydrocortal;Hydrocorticosterone;Hydrocortisone;Hydrocortisone alcohol;Hydrocortisone base;Hydrocortisone free alcohol;Hydrocortisonum;Hydrocortistab;Hydrocortisyl;Hydrocortone;Hydroskin;Hydroxycortisone;Hysone;Hytisone;Hytone;Hytone lotion;Idrocortisone;Incortin-h;Incortin-hydrogen;Kendall's compound f;Komed hc;Kyypakkaus;Lacticare hc;Lacticare-hc;Lactisona;Lubricort;Maintasone;Medicort;Meusicort;Mildison;Milliderm;Neo-cort-dome;Neosporin-h ear;Nutracort;Nystaform-hc;Optef;Otalgine;Otic-neo-cort-dome;Otobiotic;Otocort;Otosone-f;Pediotic suspension;Penecort;Permicort;Polcort h;Preparation h hydrocortisone cream;Prepcort;Prestwick_265;Prevex hc;Proctocort;Proctofoam;Protocort;Racet;Rectoid;Reichstein's substance m;Remederm hc;Sanatison;Scalpicin capilar;Schericur;Scheroson f;Sigmacort;Signef;Stiefcorcil;Synacort;Systral hydrocort;Tarcortin;Timocort;Topicort;Transderma h;Traumaide;Uniderm;Vioform-hydrocortisone;Vosol hc;Vytone;ZenoxonePW_C000045HC227449789753311218143831243673985690CorticotropinP01189M2589613888153889214434412251443451224144352122914435312261443544091443551245689Adrenocorticotropic hormone receptorQ01718BC10416913916285061414433630814433712231443401224144346122614434712271601Guanine 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 stimuliHMDBP01781GNAS20q13.3M14631138102413914415873501185516281355885991397317771399354313998748140363658140890898140893899141483949141487946143229789143306113814417672144341122414434812263625Guanine 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 interactionHMDBP08405GNG121p31.3AF188181138112413714415673500985139733777140361658140892898140895899141485949141489946144342122414434912263618GβP62873Guanine 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 interactionHMDBP08398GNB11p36.33BC0058881381224138144157735010855161869324170006308135590599136006608136181661361876651385025601397327771403626581405347871408918981408948991413755014142352141484949141488946142503741429601033143307113814434312241443501226864Adenylate cyclase type 2Q08462This is a membrane-bound, calmodulin-insensitive adenylyl cyclase.
HMDBP00921ADCY25p15.3AB02898314.6.1.138292417314136381741397357771398454814053778914060118314089989814149594814298310731430857871442858144338122414435612261315cAMP-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 fluxHMDBP01415PRKACB1p36.1AY92736612.7.11.11383723853234199813972079213989148140973314150494814152194914153778914155694714156294614164226141920658141940671419476614220083414278510501428141011142823101414418372144339122414435112263627Guanine 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 interactionHMDBP08407GNGT17q21.3BC02936715160813558959913622214139734777118Corticotropin1PW_P0001181355690146125116Adrenocorticotropic hormone receptor1PW_P0001161335689145624121Guanine nucleotide-binding protein alpha1PW_P0001211391601146420115Guanine nucleotide-binding protein alpha-beta-gamma1PW_P000115130160111313627113236181454245520922cAMP-dependent protein kinase catalytic subunit beta1PW_P0009221047131513744231122Adenylate cyclase type 21PW_P0001221408641574232465242009falsePW_R002009Right72361161ProteinComplexfalse72379861Compoundfalse72381161ProteinComplexfalse72391211ProteinComplexfalse72401201ProteinComplexfalse72419361Compoundfalse1865115596falsePW_R000596Right25164141Compoundfalse2517411Compoundfalse42001701Compoundtrue801224.6.1.119941211970falsePW_R001970Right7152411Compoundfalse7153411Compoundfalse71549221ProteinComplexfalse18169222.7.11.11182PW_T0001822141181ProteinComplex152Right1371162013-09-11T15:55:50-06:002013-09-11T15:55:50-06:00147889986122454false114068010regular50307890936122453false150067510regular5030789998654false176056010regular50307900936122453false118555010regular50307903414122482false212070010regular300280790441122482false273070010regular3002807905170122445false265364310regular6343790798654false237051010regular5030790841122482false2380125010regular3002807909423209false3135134010regular10025791042312249false2830113019regular10025791145122482false3690125010regular30028011401936122453false51555010regular5030319015842312249false257950010regular100253772569012252false12604058subunitregular150703773569012242true5955758subunitregular1507037745689122380false12204407subunitregular2001303862568912242true1753408subunitregular1507038635689122380false15404408subunitregular20013038641601122497false17655808subunitregular1507038651601122497true13555658subunitregular150703866362512242false2659258subunitregular1507038673618122498false2708708subunitregular1507038681601122497false12105508subunitregular150703869362512242false12706108subunitregular1507038703618122498false13305508subunitregular15070387786412242false21255158subunitregular150703878131512242false311013558subunitregular150703879131512242false280511458subunitregular1507059915690152false5802408subunitregular150705992569022true1003758subunitregular1507059935689122380false5504359subunitregular20013059943618122498false6755508subunitregular150705995362512242false61060010subunitregular1507059961601122497false5505508subunitregular15070123392086412242false25165158subunitregular1507012339211601122497false24015108subunitregular15070315111834212253759377231521183421224376037733153116342122337613774320311634212243849386232041163421224385038633205121342122438513864320611534212243852386538533866385438673207115342122438553868385638693857387032149223421224386438781385790911861Cofactor32159223421224386538791386791011863Cofactor49261183421559495991492711834225950599249281163425951599311762M825 585 C938 584 1155 584 1210 585 83false18trueM 562.5 347.0096189432334 L 570 360 L 577.5 347.0096189432334false11763M1330 585 C1330 555 670 545 670 515 5true1811837M1165 680 C1198 665 1212 637 1210 580 5false18trueM 1122.9509099759564 497.71939584077154 L 1115 485 L 1107.96013506908 498.2453879427672false11838M1525 675 C1532 627 1375 610 1345 610 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false11839M1345 555 C1343 630 1300 585 1330 585 5false1811840M1580 510 C1518 510 1507 512 1420 510 5false18trueM 1086.4522906520851 484.9295295258044 L 1085 470 L 1072.7967934901462 478.72248536128666false11841M1765 615 C1735 615 1622 612 1345 610 5false18trueM 1447.0096189432334 582.5 L 1460 575 L 1447.0096189432334 567.5false11842M420 905 C947 897 1343 816 1345 680 5false18trueM 1312.4327880140777 429.77868135590376 L 1315 415 L 1300.9176805183909 420.16606988124335false11853M2270 700 C2273 654 2306 577 2395 550 5false1811854M2880 700 C2878 558 2763 552 2666 550 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false11855M2684.5 643 C2694.5 607 2682 581 2665 545 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false11857M2200 515 C2243 487 2353 479 2476 510 83false18trueM 1775.1056379553524 393.2229295785013 L 1790 395 L 1784.091807107008 381.21256888542325false11858M1915 615 C2008 506 2341 428 2476 510 83false1811859M2880 980 C2880 1010 2880 1115 2880 1145 5false1811860M2680 1390 C2776 1388 2883 1284 2880 1215 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false11861M2815 1510 L2815 1560 L2865 1510 z10true1811862M3110 1390 C3009 1389 2882 1287 2880 1215 5false18trueM 2405.5346305556136 1283.9690158525025 L 2420 1280 L 2409.3300467215167 1269.4571305122854false11863M250 235 L250 285 L300 235 z10true1811864M3690 1390 C3660 1390 3591 1390 3561 1390 5false18trueM 2967.0096189432334 1287.5 L 2980 1280 L 2967.0096189432334 1272.5false11865M3260 1390 C3290 1390 3381 1390 3411 1390 5false18trueM 2708.0096189432334 1287.5 L 2721 1280 L 2708.0096189432334 1272.5false17801M655 310 C655 340 655 430 655 460 83false18trueM 547.5 357.0096189432334 L 555 370 L 562.5 357.0096189432334false17802M175 375 C175 345 675 580 675 550 5true182316342200912247753788911837Left7754789011838Right110320311839Left111320411840Right112320511841Right113320611842Right234618653207231834259612247757790311853Left7758790411854Right7759790511855Right2319342197012247760790411859Left7761790811860Right114321411862Right2350181632152901823427315111762Left8315211763Right173315313742618234253492617801Left54492717802Right277492813772964834214false3411135516regular693791111864Right417321411865Left167899177900187907721140194173190158251185726118587387736599437599538599664401233920644112339215347124201000.80.802829240018594212408021.61.60390484497550M315 605 C315 555 365 505 415 505 C1497 505 2902 505 3984 505 C4034 505 4084 555 4084 605 C4084 907 4084 1300 4084 1602 C4084 1652 4034 1702 3984 1702 C2902 1702 1497 1702 415 1702 C365 1702 315 1652 315 1602 C315 1300 315 907 315 605 1true63769.01197.042615Regulatory subunit25601120201.61.61601542715Regulatory subunit22401205201.61.61601542815Activation530320201.61.61601542915Activation2170390201.61.61601543015Activation27351010201.61.61601543115Activation32051410201.61.61601543215Intracellular Space350735201.61.616015433235Adrenal Cortex 2375205201.61.62001543415Extracellular Space0740201.61.6160152712577176252437415017574438981320