158PathwayCilazapril 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 MetabolismPW000568CenterPathwayVisualizationContext63813601000#000099PathwayVisualization145158Cilazapril 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.Drug1403Cilazaprilat inhibition of ACEInhibitorySubPathway88040471Compound29617725ProteinComplex29393Bader, M. Renin-angiotensin-aldosterone system. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (2004) p.810-814. Berlin, Germany: Springer.158Pathway394Inhibace. (2009). e-CPS (online version of Compendium of Pharmaceuticals and Specialties). Retrieved August 22, 2009.158Pathway395Peters, J. ACE inhibitors. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (2004) p. 2-5. Berlin, Germany: Springer.158Pathway396Stanfield, C.L., & Germann, W.J. Principles of human physiology (3rd ed.) (2008). San Francisco, CA: Pearson Education, Inc.;158Pathway2796641712267Szucs T: Cilazapril. A review. Drugs. 1991;41 Suppl 1:18-24. doi: 10.2165/00003495-199100411-00005.158Pathway1CellCL: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_BS0000149708CilazaprilHMDB0015433Cilazapril is only found in individuals that have used or taken this drug. It is one of the angiotensin-converting enzyme inhibitors (ACE inhibitors) used for hypertension. It is a prodrug that is hydrolyzed after absorption to its main metabolite cilazaprilat. [PubChem]Cilazapri, as a pyridazine ACE inhibitor, competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. As angiotensin II is a vasoconstrictor and a negative feedback mediator for renin activity, lower angiotensin II levels results in a decrease in blood pressure, an increase in renin activity, and stimulation of baroreceptor reflex mechanisms. Kininase II, an enzyme which degrades the vasodilator bradykinin, is identical to ACE and may also be inhibited.88768-40-54046688855365550831DB01340CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CCCN2CCC[C@H](N2C1=O)C(O)=OC22H31N3O5InChI=1S/C22H31N3O5/c1-2-30-22(29)18(13-12-16-8-4-3-5-9-16)23-17-10-6-14-24-15-7-11-19(21(27)28)25(24)20(17)26/h3-5,8-9,17-19,23H,2,6-7,10-15H2,1H3,(H,27,28)/t17-,18-,19-/m0/s1HHHKFGXWKKUNCY-FHWLQOOXSA-N(1S,9S)-9-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}-10-oxo-octahydro-1H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid417.4986417.226371117-2.592inhibace0-1InhibacePW_C009708Cilazpl33112940471CilazaprilatHMDB0061258Cilazaprilat 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. Cilazaprilat is slightly soluble (in water) and a weakly acidic compound (based on its pKa).90139-06-3C173096476658300OC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CCCN2CCC[C@H](N2C1=O)C(O)=OC20H27N3O5InChI=1S/C20H27N3O5/c24-18-15(8-4-12-22-13-5-9-17(20(27)28)23(18)22)21-16(19(25)26)11-10-14-6-2-1-3-7-14/h1-3,6-7,15-17,21H,4-5,8-13H2,(H,25,26)(H,27,28)/t15-,16-,17-/m0/s1UVAUYSRYXACKSC-ULQDDVLXSA-N(1S,9S)-9-{[(1S)-1-carboxy-3-phenylpropyl]amino}-10-oxo-octahydro-1H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid389.4455389.195070989-2.143(1S,9S)-9-{[(1S)-1-carboxy-3-phenylpropyl]amino}-10-oxo-octahydropyridazino[1,2-a][1,2]diazepine-1-carboxylic acid0-1DBMET01138(1s,9s)-9-((s)-1-carboxy-3-phenylpropylamino)-10-oxo-4,6,7,8,9,10-hexahydro-1h-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid;(1s,9s)-9-((s)-1-carboxy-3-phenylpropylamino)-10-oxo-4,6,7,8,9,10-hexahydro-1h-pyridazino[1,2-a][1,2]diazepine-1-carboxylatePW_C040471Cilazpt3312294409511005Zinc (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_P00072581915603231005232437422905151723falsePW_R001723Right652897081Compoundfalse6529404711Compoundfalse229PW_T000229266404711Compound2951Right6562970829157false20036010regular20019065634047129157false59036010regular200190657640471293true29062010regular10010065771005299false695113510regular100256578374299false695107010regular1002591494047151157false165102010regular20019027931560292false67010808subunitregular15070246672514529278227931080657710016Cofactor1081657810017Cofactor9999M400 455 C458 455 541 454 590 455 5false18trueM 381.85929394075333 227.23338401195997 L 395 220 L 382.16535266069116 212.23650673500828false10000M590 455 C560 455 151 33 175 50 5true18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false10015M365 1115 C385 1115 646 1115 670 1115 148false18falsetrueM 570.0012648088053 709.8052112312832 L 585 710 L 599.9987351911947 710.194788768716810016M550 150 L550 200 L600 150 z10true1810017M550 150 L550 200 L600 150 z10true1810018M670 1115 C640 1115 622 695 592 695 5true1814394M690 550 C690 580 701 273 725 290 5true1814395M265 1020 C270 887 690 692 690 550 83false18trueM 258.1365968090576 841.6623204177578 L 265 855 L 273.1190677502876 842.3872786891076false1972145172329692665629999Left6927656310000Right362229145809656314394Left810914914395Right57540314514true44266016regular561657610015Left248246610018Right4397215101.31.302920014544074107250.80.80211580250649M110 365 C110 315 160 265 210 265 C385 265 611 265 786 265 C836 265 886 315 886 365 C886 422 886 496 886 553 C886 603 836 653 786 653 C611 653 385 653 210 653 C160 653 110 603 110 553 C110 496 110 422 110 365 1true6776.0388.021717481161923949130044888377332831185020594771244897507