487PathwayZalcitabine Action PathwayZalcitabine (ddc) is a dideoxynucleoside antiretroviral drug that when used in combination with zidovudine improves the viral load and CD4+ cell count of patients infected with Human Immunodeficiency Virus Type 1 (HIV-1). Zalcitabine is phosphorylated to it’s active form metabolite 2′,3′-dideoxycytidine 5′-triphosphate (ddCTP) in both healthy and infected cells. ddCTP competes with deoxycytidine triphosphate inhibiting the enzyme reverse transcriptase from using the substrates to elongate the viral DNA strand ultimately halting HIV replication.Drug ActionPW000723TopPathwayVisualizationContext100510001000#000099PathwayVisualization468487Zalcitabine PathwayZalcitabine (ddc) is a dideoxynucleoside antiretroviral drug that when used in combination with zidovudine improves the viral load and CD4+ cell count of patients infected with Human Immunodeficiency Virus Type 1 (HIV-1). Zalcitabine is phosphorylated to it’s active form metabolite 2′,3′-dideoxycytidine 5′-triphosphate (ddCTP) in both healthy and infected cells. ddCTP competes with deoxycytidine triphosphate inhibiting the enzyme reverse transcriptase from using the substrates to elongate the viral DNA strand ultimately halting HIV replication.Drug12801498598838487Pathway2803669179531Adkins JC, Peters DH, Faulds D: Zalcitabine. An update of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in the management of HIV infection. Drugs. 1997 Jun;53(6):1054-80. doi: 10.2165/00003495-199753060-00009.487Pathway2803678097417Shelton MJ, O'Donnell AM, Morse GD: Zalcitabine. Ann Pharmacother. 1993 Apr;27(4):480-9. doi: 10.1177/106002809302700416.487Pathway9386ZalcitabineHMDB0015078A dideoxynucleoside compound in which the 3'-hydroxyl group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of 5' to 3' phosphodiester linkages, which are needed for the elongation of DNA chains, thus resulting in the termination of viral DNA growth. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [PubChem]7481-89-2C07207240661010122498DB00943NC1=NC(=O)N(C=C1)[C@H]1CC[C@@H](CO)O1C9H13N3O3InChI=1S/C9H13N3O3/c10-7-3-4-12(9(14)11-7)8-2-1-6(5-13)15-8/h3-4,6,8,13H,1-2,5H2,(H2,10,11,14)/t6-,8+/m0/s1WREGKURFCTUGRC-POYBYMJQSA-N4-amino-1-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one211.2178211.095691297-1.482zalcitabine00Dideoxycytidine;Ddc;Ddcyd;2',3'-dideoxycytidine;4-amino-1-[(2r,5s)-5-(hydroxymethyl)tetrahydrofuran-2-yl]pyrimidin-2(1h)-onePW_C009386ddC40734Dideoxycytidine 5'-TriphosphateHMDB0061726Dideoxycytidine 5'-triphosphate, also known as 2',3'-DDCTP or DDCTP-2',3', belongs to the class of organic compounds known as pyrimidine 2',3'-dideoxyribonucleoside triphosphates. These are pyrimidine nucleotides with triphosphate group linked to the ribose moiety lacking a hydroxyl group at positions 2 and 3. Dideoxycytidine 5'-triphosphate is slightly soluble (in water) and an extremely strong acidic compound (based on its pKa). In humans, dideoxycytidine 5'-triphosphate is involved in the zalcitabine action pathway.119119106431[H][C@@]1(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)CC[C@@]([H])(O1)N1C=CC(=N)N=C1OC9H16N3O12P3InChI=1S/C9H16N3O12P3/c10-7-3-4-12(9(13)11-7)8-2-1-6(22-8)5-21-26(17,18)24-27(19,20)23-25(14,15)16/h3-4,6,8H,1-2,5H2,(H,17,18)(H,19,20)(H2,10,11,13)(H2,14,15,16)/t6-,8+/m0/s1ARLKCWCREKRROD-POYBYMJQSA-N{[hydroxy({[hydroxy({[(2S,5R)-5-(2-hydroxy-4-imino-1,4-dihydropyrimidin-1-yl)oxolan-2-yl]methoxy})phosphoryl]oxy})phosphoryl]oxy}phosphonic acid451.1575450.994682527-1.676[hydroxy({hydroxy[(2S,5R)-5-(2-hydroxy-4-iminopyrimidin-1-yl)oxolan-2-yl]methoxyphosphoryl}oxy)phosphoryl]oxyphosphonic acid0-32'3'-dideoxycytidine 5'-triphosphate;2'3'-dideoxycytidine 5'-triphosphoric acid;Dideoxycytidine 5'-triphosphoric acidPW_C040734D5T78Reverse TranscriptaseProteinComplexPW_EC000078Q9WJQ2UniProtRT2346falsePW_R002346Right906193861Compoundfalse9062407341Compoundfalse119019386157false23543010regular2001901190240734157false55042510regular20020031278144false57572512regular1507018570M435 525 C465 525 526 508 550 525 5true1818571M550 525 C520 525 487 525 435 525 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false18572M651 622 C651 653 650 693 650 725 148false18falsetrueM 443 322 L 458 322 L 473 32233564682346110911190118570Left110921190218571Right2241857231312101574210351.01.00211580250803M135 450 C135 400 185 350 235 350 C389 350 589 350 743 350 C793 350 843 400 843 450 C843 549 843 678 843 777 C843 827 793 877 743 877 C589 877 389 877 235 877 C185 877 135 827 135 777 C135 678 135 549 135 450 1true6708.0527.05294311575728991594444858655CenterPathwayVisualizationContext100613001700#000099PathwayVisualization336295Viral Transcription InhibitionDrug11CellCL:00000002Platelet CL:00002335HepatocyteCL:00001823NeuronCL:00005404Cardiomyocyte CL:00007468Beta cellCL:00006397Epithelial CellCL:00000661Homo sapiens9606EukaryoteHuman2Bacteria2ProkaryoteBacteria3Escherichia coli562Prokaryote12Mus musculus10090EukaryoteMouse17Rattus norvegicus10116EukaryoteRat19Schizosaccharomyces pombe4896Eukaryote24Solanum lycopersicum4081EukaryoteTomato4Arabidopsis thaliana3702EukaryoteThale cress18Saccharomyces cerevisiae4932EukaryoteYeast21Xenopus laevis8355EukaryoteAfrican clawed frog6Caenorhabditis elegans6239EukaryoteRoundworm25Escherichia coli (strain K12)83333Prokaryote49Bathymodiolus platifrons220390EukaryoteDeep sea mussel23Pseudomonas aeruginosa287Prokaryote60Nitzschia sp.0001EukaryoteNitzschia45Bos taurus9913EukaryoteCattle10Drosophila melanogaster7227EukaryoteFruit fly51Picea sitchensis3332EukaryoteSitka spruce1CytosolGO:00058293Mitochondrial MatrixGO:00057595CytoplasmGO:000573714Mitochondrial Outer MembraneGO:00057412MitochondrionGO:000573915NucleusGO:00056344PeroxisomeGO:000577713Endoplasmic ReticulumGO:00057837Endoplasmic Reticulum MembraneGO:000578910Cell MembraneGO:000588627Peroxisome MembraneGO:000577831Periplasmic SpaceGO:000562011Extracellular SpaceGO:000561535ChloroplastGO:000950712Mitochondrial Inner MembraneGO:000574332Inner MembraneGO:00702582Endothelium BTO:00003931LiverBTO:00007597297Nervous SystemBTO:000148418PancreasBTO:000098825IntestineBTO:00006488Blood VesselBTO:000110274112111PW_BS0000024311PW_BS0000048511PW_BS00000816212PW_BS000016221411PW_BS00002213121PW_BS0000133211515PW_BS0000325411PW_BS000005397113PW_BS0000393211PW_BS000003181311PW_BS000018101711PW_BS00001049711PW_BS00004914101PW_BS0000145811411PW_BS000058592711PW_BS00005927151PW_BS00002746114PW_BS00004629111PW_BS0000296618518PW_BS00006672513PW_BS000072612517PW_BS0000615181PW_BS000051231511PW_BS000023311511PW_BS000031918511PW_BS000091541315PW_BS000054892PW_BS000089261115PW_BS000026711PW_BS000007971521PW_BS000097100521PW_BS0001001041431PW_BS000104101531PW_BS0001011115121PW_BS0001111122121PW_BS000112103331PW_BS000103117131PW_BS0001171181171PW_BS0001181203171PW_BS00012012915121PW_BS0001291321121PW_BS0001321333121PW_BS0001331355171PW_BS00013510813PW_BS00010814315191PW_BS0001431465191PW_BS000146107313PW_BS0001071471241PW_BS000147151141PW_BS0001511553241PW_BS0001551613181PW_BS00016116611PW_BS0001661783211PW_BS000178188118PW_BS0000241601181PW_BS00016019914181PW_BS000024205561PW_BS000024206261PW_BS00002421013181PW_BS0000242137181PW_BS0000242111018PW_BS0000241985181PW_BS0000242164181PW_BS0000242171518PW_BS00002421815181PW_BS0000241632181PW_BS000163222341PW_BS0000241901118PW_BS0000242253541PW_BS0000242771218PW_BS00002417018PW_BS0001702811251PW_BS0000241644PW_BS0001642851041PW_BS000024226441PW_BS0000242905491PW_BS0000242231241PW_BS0000243081011PW_BS000024315123PW_BS0000243221231PW_BS0000243183123PW_BS000024253541PW_BS00002413412121PW_BS00013432914121PW_BS0000283331212PW_BS0000283361121PW_BS00002833217121PW_BS000028350114121PW_BS00002812815121PW_BS0001283511512PW_BS00002835325127PW_BS00002833527121PW_BS0000281151012PW_BS00011513013121PW_BS0001303317121PW_BS0000283344121PW_BS0000283683601PW_BS000028184121PW_BS0000241192171PW_BS00011911PW_BS000001124151PW_BS000124943PW_BS000094388161PW_BS000112109323PW_BS000109122551PW_BS000122406351PW_BS000115407251PW_BS0001153821451PW_BS000100412125PW_BS000115429151PW_BS0001151231751PW_BS00012343311451PW_BS000115408451PW_BS0001154101551PW_BS0001151251351PW_BS000125383751PW_BS000100405105PW_BS0001154222751PW_BS000115435155PW_BS00011539914171PW_BS0001134461217PW_BS0001154641171PW_BS00011544717171PW_BS000115468114171PW_BS0001153744171PW_BS00005344415171PW_BS00011513613171PW_BS0001363987171PW_BS0001133761017PW_BS00005347225177PW_BS00011537527171PW_BS0000534701517PW_BS0001152975101PW_BS0000244793101PW_BS0001152991101PW_BS0000244812101PW_BS00011548414101PW_BS00011548515101PW_BS00011530013101PW_BS0000244957101PW_BS0001154781010PW_BS00011549127101PW_BS0001154991510PW_BS000115501361PW_BS0001153891461PW_BS0001125161561PW_BS0001153951361PW_BS000113390761PW_BS000112209106PW_BS0000245082761PW_BS000115517156PW_BS000115502461PW_BS0001152491341PW_BS0000242881441PW_BS00002430635511PW_BS000024171211PW_BS000017372102PW_BS0000283841251PW_BS0001003911261PW_BS00011212112171PW_BS000121414Adenosine 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_C000414ATP9221460826616414224781373332799593439976321051821121021464921561421605824055924342727264628122930296631637236166136175143992344743147689148645450328950352651557520597521510052501045291101531311153461125390103540611754301185443120554212955561325569133560313556211085846143585414658761075897147592415160481556109161623016664931786839188687016069761997157205718420672092107225213722921172981987302216739021774082187432163748122274991908186225118472771190317012010281120391641217828512578226126912901326422315327308423263154262132242694318770282537721813477233329774683337763233678037332780413507816812878214351782403537841133578494115788501307886533178919334800283688004618480674119856291948261241132349411328238811628010911991412211999240612015440712024538212036241212124642912139212312139743312147140812197441012206512512207938312208340512240242212244443512291939912300944612381646412395144712395646812402937412452744412461613612463039812463437612494347212497237512501147012530429712537147912539229912551548112559548412612348512622030012623449512624047812654749112659649912691350112712338912773151612778139512779639012780120912811950812816751732Adenosine monophosphateHMDB0000045Adenosine monophosphate, also known as 5'-adenylic acid and abbreviated AMP, is a nucleotide that is found in RNA. It is an ester of phosphoric acid with the nucleoside adenosine. AMP consists of the phosphate group, the pentose sugar ribose, and the nucleobase adenine. AMP can be produced during ATP synthesis by the enzyme adenylate kinase. AMP has recently been approved as a 'Bitter Blocker' additive to foodstuffs. When AMP is added to bitter foods or foods with a bitter aftertaste it makes them seem 'sweeter'. This potentially makes lower calorie food products more palatable.61-19-8C00020608316027AMP5858DB00131NC1=C2N=CN([C@@H]3O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]3O)C2=NC=N1C10H14N5O7PInChI=1S/C10H14N5O7P/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(22-10)1-21-23(18,19)20/h2-4,6-7,10,16-17H,1H2,(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1UDMBCSSLTHHNCD-KQYNXXCUSA-N{[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}phosphonic acid347.2212347.063084339-2.025adenylate0-2DBMET00485FDB0218065'-amp;5'-adenosine monophosphate;5'-adenylate;5'-adenylic acid;Amp;Adenosine 5'-monophosphate;Adenosine 5'-phosphate;Adenosine 5'-phosphorate;Adenosine 5'-phosphoric acid;Adenosine phosphate;Adenosine-5'-monophosphorate;Adenosine-5'-monophosphoric acid;Adenosine-5-monophosphorate;Adenosine-5-monophosphoric acid;Adenosine-monophosphate;Adenosine-phosphate;Adenovite;Adenylate;Adenylic acid;Cardiomone;Lycedan;Muscle adenylate;Muscle adenylic acid;My-b-den;My-beta-den;Phosaden;Phosphaden;Phosphentaside;5'-o-phosphonoadenosine;Adenosine 5'-(dihydrogen phosphate);Adenosine monophosphate;Adenosine-5'p;Adenosini phosphas;Ado5'p;Fosfato de adenosina;Pa;Pado;Phosphate d'adenosine;5'-adenosine monophosphoric acid;Adenosine phosphoric acid;Adenosine 5'-(dihydrogen phosphoric acid);Adenosine 5'-monophosphoric acid;Adenosine monophosphoric acid;Adenosine-5'-monophosphate;Phosphoric acid d'adenosinePW_C000032AMP112344628270167343288122118914457254867545033895251104540811754231035432118545712055581325583133577910157951086977199707218811789198118681611198815112003222125802261263631126942901333122542266342646315772343297732511178392334788091157932011280399180684135809007119916122120016124120031406120246382120888405121954408122920399123464376124507374125306297125394299125409479125596484126853205126934388126949501127124389127311209127711502170PyrophosphateHMDB0000250The 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_C000170Ppi12235463842923735328822212173162049241059281529417514486854503489525210452941015409117542410354331185458120554811155591325584133560613556551085879107623916669781997073188713416372721607312198731821382751518283210118691611200222212041164123152251232324912512288125792261269529015219306153751834760174256131542697318772353297731712877635336784163357892833179153112799501347995813080047372804171708563019478638494814125948193829867822311063439111327039511327538911552713611553239911993412212001712412003240612033041012093640712126142912134112112148638312240742212298544412350211912383146412404439812497737512532429712539529912541047912559748412565648512587648112655249112686920512693538812695050112733720612812450878Reverse TranscriptaseProteinComplexPW_EC000078Q9WJQ2UniProtRT1959falsePW_R001959Right71254141Compoundfalse7126321Compoundfalse71271701Compoundfalse115574143242false113643710regular503011558323244false124760810regular5030115591703245false112765710regular634329078197false77037512regular30014018023M1161 467 C1161 497 1161 523.25 1161 545.25 5false1818024M1247 623 C1212 616 1163 567.25 1161 535.25 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false18025M1158.5 657 C1158.5 624 1161 599.25 1161 535.25 5false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false18030M1056 635 C1014 652 986 663 944 681 195false183296336195932108861155718023Left108871155818024Right108881155918025Right19918030132909131934403450.60.6024315001130702M134 284 C134 234 184 184 234 184 C604 184 1086 184 1456 184 C1506 184 1556 234 1556 284 C1556 529 1556 849 1556 1094 C1556 1144 1506 1194 1456 1194 C1086 1194 604 1194 234 1194 C184 1194 134 1144 134 1094 C134 849 134 529 134 284 1true61422.01010.092515DNA535415201.01.01601592615Viral RNA560895201.01.01601592715Chain termination840655201.01.016015