167PathwaySpirapril Metabolism PathwayBenazepril, brand name Lotensin, belongs to the class of drugs known as angiotensin-converting enzyme (ACE) inhibitors and is used primarily to lower high blood pressure (hypertension). This drug can also be used in the treatment of congestive heart failure and type II diabetes. Benazepril is a prodrug which, following oral administration, undergoes biotransformation in vivo into its active form benazeprilat via cleavage of its ester group by the liver. Angiotensin-converting enzyme (ACE) is a component of the body's renin–angiotensin–aldosterone system (RAAS) and cleaves inactive angiotensin I into the active vasoconstrictor angiotensin II. ACE (or kininase II) also degrades the potent vasodilator bradykinin. Consequently, ACE inhibitors decrease angiotensin II concentrations and increase bradykinin concentrations resulting in blood vessel dilation and thereby lowering blood pressure.Drug MetabolismPW000574CenterPathwayVisualizationContext64414001000#000099PathwayVisualization154167Spirapril PathwayBenazepril, brand name Lotensin, belongs to the class of drugs known as angiotensin-converting enzyme (ACE) inhibitors and is used primarily to lower high blood pressure (hypertension). This drug can also be used in the treatment of congestive heart failure and type II diabetes. Benazepril is a prodrug which, following oral administration, undergoes biotransformation in vivo into its active form benazeprilat via cleavage of its ester group by the liver. Angiotensin-converting enzyme (ACE) is a component of the body's renin–angiotensin–aldosterone system (RAAS) and cleaves inactive angiotensin I into the active vasoconstrictor angiotensin II. ACE (or kininase II) also degrades the potent vasodilator bradykinin. Consequently, ACE inhibitors decrease angiotensin II concentrations and increase bradykinin concentrations resulting in blood vessel dilation and thereby lowering blood pressure.Drug1538spiraprilat inhibition of ACEInhibitorySubPathway88440475Compound51885725ProteinComplex51427Bader, M. Renin-angiotensin-aldosterone system. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (2004) p.810-814. Berlin, Germany: Springer.167Pathway428Peters, J. ACE inhibitors. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (2004) p. 2-5. Berlin, Germany: Springer.167Pathway429Stanfield, C.L., & Germann, W.J. Principles of human physiology (3rd ed.) (2008). San Francisco, CA: Pearson Education, Inc.;167Pathway27967310499560Hayduk K, Kraul H: Efficacy and safety of spirapril in mild-to-moderate hypertension. J Cardiovasc Pharmacol. 1999 Aug;34 Suppl 1:S19-23.167Pathway1CellCL:00000002Platelet CL:00002337Epithelial CellCL:00000661Homo sapiens9606EukaryoteHuman3Escherichia coli562Prokaryote17Rattus norvegicus10116EukaryoteRat12Mus musculus10090EukaryoteMouse18Saccharomyces cerevisiae4932EukaryoteYeast4Arabidopsis thaliana3702EukaryoteThale cress49Bathymodiolus platifrons220390EukaryoteDeep sea mussel5Bos taurus9913EukaryoteCattle10Drosophila melanogaster7227EukaryoteFruit fly6Caenorhabditis elegans6239EukaryoteRoundworm1CytosolGO:00058293Mitochondrial MatrixGO:00057595CytoplasmGO:000573711Extracellular SpaceGO:00056154PeroxisomeGO:000577735ChloroplastGO:000950710Cell MembraneGO:00058861LiverBTO:00007597298Blood VesselBTO:000110274112Endothelium BTO:000039328StomachBTO:00013071552626LungBTO:000076329111PW_BS0000295181PW_BS0000512111PW_BS0000024311PW_BS0000048511PW_BS00000816212PW_BS00001615111PW_BS000015682512PW_BS0000687028511PW_BS000070117131PW_BS000117103331PW_BS0001031181171PW_BS0001181203171PW_BS0001201321121PW_BS0001321333121PW_BS0001331355171PW_BS00013516611PW_BS0001661985181PW_BS000024226441PW_BS0000242905491PW_BS000024151141PW_BS0001512253541PW_BS0000241115121PW_BS0001111141112PW_BS0001143361121PW_BS00002811PW_BS000001124151PW_BS000124406351PW_BS000115122551PW_BS000122409115PW_BS000115429151PW_BS0001151371117PW_BS0001374641171PW_BS0001152991101PW_BS0000244793101PW_BS0001152975101PW_BS0000244831110PW_BS000115388161PW_BS000112501361PW_BS000115205561PW_BS000024208116PW_BS000024711PW_BS0000071901118PW_BS0000246612617PW_BS00050814101PW_BS0000149713SpiraprilHMDB0015438Spirapril is an ACE inhibitor antihypertensive drug used to treat hypertension. Like many ACE inhibitors, this is a prodrug which is converted to the active metabolite spiraprilat following oral administration. ACE inhibitors are used primarily in treatment of hypertension and congestive heart failure.83647-97-6404797411019674470933DB01348CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CC2(C[C@H]1C(O)=O)SCCS2C22H30N2O5S2InChI=1S/C22H30N2O5S2/c1-3-29-21(28)17(10-9-16-7-5-4-6-8-16)23-15(2)19(25)24-14-22(30-11-12-31-22)13-18(24)20(26)27/h4-8,15,17-18,23H,3,9-14H2,1-2H3,(H,26,27)/t15-,17-,18-/m0/s1HRWCVUIFMSZDJS-SZMVWBNQSA-N(8S)-7-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid466.614466.15961346-4.202spirapril0-1RenormaxPW_C009713Spirap33232940475SpiraprilatHMDB0061261SPIRAPRILAT,Also known as spiraprilate or spiraprilic acid, belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond. SPIRAPRILAT is considered to be a practically insoluble (in water) and relatively neutral molecule. SPIRAPRILAT can be converted into spirapril..30337022298317C[C@H](N[C@@H](CCC1=CC=CC=C1)C(O)=O)C(=O)N1CC2(C[C@H]1C(O)=O)SCCS2C20H26N2O5S2InChI=1S/C20H26N2O5S2/c1-13(21-15(18(24)25)8-7-14-5-3-2-4-6-14)17(23)22-12-20(28-9-10-29-20)11-16(22)19(26)27/h2-6,13,15-16,21H,7-12H2,1H3,(H,24,25)(H,26,27)/t13-,15-,16-/m0/s1FMMDBLMCSDRUPA-BPUTZDHNSA-N(8S)-7-[(2S)-2-{[(1S)-1-carboxy-3-phenylpropyl]amino}propanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid438.561438.128313332-4.173spiraprilat0-1DBMET01142Sch-33861spiraprilatPW_C040475Splat3324294417511005Zinc (II) ionHMDB0001303Zinc is an essential element, necessary for sustaining all life.Physiologically, it exists as an ion in the body. It is estimated that 3000 of the hundreds of thousands of proteins in the human body contain zinc prosthetic groups. In addition, there are over a dozen types of cells in the human body that secrete zinc ions, and the roles of these secreted zinc signals in medicine and health are now being actively studied. Intriguingly, brain cells in the mammalian forebrain are one type of cell that secretes zinc, along with its other neuronal messenger substances. Cells in the salivary gland, prostate, immune system and intestine are other types that secrete zinc. Obtaining a sufficient zinc intake during pregnancy and in young children is a problem, especially among those who cannot afford a good and varied diet. Brain development is stunted by zinc deficiency in utero and in youth. Zinc is an activator of certain enzymes, such as carbonic anhydrase. Carbonic anhydrase is important in the transport of carbon dioxide in vertebrate blood. Even though zinc is an essential requirement for a healthy body, too much zinc can be harmful. Excessive absorption of zinc can also suppress copper and iron absorption. The free zinc ion in solution is highly toxic to plants, invertebrates, and even vertebrate fish. The Free Ion Activity Model (FIAM) is well-established in the literature, and shows that just micromolar amounts of the free ion kills some organisms.23713-49-7C000383205129105ZN%2b229723DB01593[Zn++]ZnInChI=1S/Zn/q+2PTFCDOFLOPIGGS-UHFFFAOYSA-Nzinc(2+) ion65.40963.9291465780zinc(2+) ion22FDB003729Zinc;Zinc ion;Dietary zinc;Zinc cation;Zinc, ion (zn2+);Zn(ii);Zn(2+);Zn2+PW_C001005Zinc13238411882711652915295751304468312029314770541011754251035434118545912055601325585133559813574491661178719812466226127242901332115176967225774011117758011477929336804001120020124120035406120060122120441409121257429123075137123827464125398299125413479125438297125685483126938388126953501126976205127180208374Chloride ionHMDB0000492Under standard conditions, chlorine exists as a diatomic molecule. Chlorine is a highly toxic, pale yellow-green gas that has a specific strong smell. In nature, chlorine is most abundant as a chloride ion. Physiologically, this it. exists as an ion in the body. The chloride ion is an essential anion that the body needs for many critical functions. It also helps keep the body's acid-base balance. The amount of chloride in the blood is carefully controlled by the kidneys. Chloride ions have important physiological roles. For instance, in the central nervous system, the inhibitory action of glycine and some of the action of GABA relies on the entry of Cl- into specific neurons. Also, the chloride-bicarbonate exchanger biological transport protein relies on the chloride ion to increase the blood's capacity of carbon dioxide, in the form of the bicarbonate ion. Chloride-transporting proteins (CLC) play fundamental roles in many tissues in the plasma membrane as well as in intracellular membranes. CLC proteins form a gene family that comprises nine members in mammals, at least four of which are involved in human genetic diseases. GABA(A) receptors are pentameric complexes that function as ligand-gated chloride ion channels. WNK kinases are a family of serine-threonine kinases that have been shown to play an essential role in the regulation of electrolyte homeostasis, and they are found in diverse epithelia throughout the body that are involved in chloride ion flux. Cystic fibrosis (CF) is caused by alterations in the CF transmembrane conductance regulator (CFTCR) gene that result in deranged sodium and chloride ion transport channels. (PMID: 17539703, 17729441, 17562499, 15300163) (For a complete review see Evans, Richard B. Chlorine: state of the art. Lung (2005), 183(3), 151-167. PMID: 16078037).16887-00-6C0069831217996CPD-4521306[Cl-]ClInChI=1S/ClH/h1H/p-1VEXZGXHMUGYJMC-UHFFFAOYSA-Mchloride35.45334.9688527070chloride-1-1FDB006557Bertholite;Chloor;Chlor;Chlore;Chloride;Chloride ion;Chlorine;Chlorine gas;Cl;Cl2;Diatomic chlorine;Dichlorine;Molecular chlorine;Chloride(1-);Chlorine anion;Cl(-)PW_C000374Cl2091152092229585131498331629343777282190789091141223714091249251371560Angiotensin-converting enzymeP12821Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent vasodilator. Has also a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moietyHMDBP01710ACE17q23.3EU33284013.2.1.-; 3.4.15.129101529595133172913616166113654814725Angiotensin-converting enzyme1PW_P00072581915603231005232437422905151727falsePW_R001727Right653897131Compoundfalse6539404751Compoundfalse234PW_T000234271404751Compound2951Right6586971329157false22541510regular20019065874047529157false57041510regular20019065961005519false675119010regular100256597374519false670112510regular1002591594047551157false180107510regular20019027981560512false65011358subunitregular15070247172515451278727981090659610045Cofactor1091659710046Cofactor10028M425 510 C455 510 536 509 570 510 5false18trueM 1641.7947410904374 887.1148532754665 L 1655 880 L 1642.2357268644657 872.1213369585013false10029M570 510 C540 510 151 33 175 50 5true18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false10044M770 510 C800 510 867.5 950 897.5 950 5true1810045M1195 990 L1195 1040 L1245 990 z10true1810046M1195 990 L1195 1040 L1245 990 z10true1810047M650 1170 C627 1169 402 1170 380 1170 148false18falsetrueM 695.0636766781066 1686.38066854236 L 710 1685 L 724.9363233218934 1683.6193314576414412M770 510 C800 510 786 873 810 890 5true1814413M280 1075 C282 937 671 766 670 605 83false18trueM 272.6890341491101 1061.9022987388198 L 280 1075 L 287.6874590979166 1062.1196672163387false19771541727296940658610028Left6941658710029Right367234154819658714412Left820915914413Right58353815414true89791516regular565658710044Left253247110047Right4427220201.41.402920014544374207900.80.80211580250655M120 400 C120 350 170 300 220 300 C390 300 610 300 780 300 C830 300 880 350 880 400 C880 468 880 557 880 625 C880 675 830 725 780 725 C610 725 390 725 220 725 C170 725 120 675 120 625 C120 557 120 468 120 400 1true6760.0425.02191828655110039471352448963492221071205724294378544886543