Metabolism of angiotensinogen to angiotensins (Homo sapiens)

From WikiPathways

Revision as of 10:04, 11 June 2014 by ReactomeTeam (Talk | contribs)
Jump to: navigation, search
3, 13, 19, 22, 26...2, 8, 23, 4314, 28, 3421, 401, 4, 9, 12, 30...1, 4, 9, 12, 24...5, 4420312, 8210, 14, 18, 28, 34...6, 17, 25214, 28, 347, 11, 25, 322Prorenin-ProreninReceptor [plasmamembrane]Renin:ProreninReceptor [plasmamembrane]cytosolANPEP Dimer [plasmamembrane]ENPEP Dimer [plasmamembrane]plasma membraneH2OaliskirenENPEP DimerAGT(34-40)H2OH2OMMEACE2(18-805)CTSZlisinoprilH2ORenin:ProreninReceptorACE(30-1306)ReninAGTH2OAGT(35-41)ANPEP DimerANPEP [plasmamembrane]Cathepsin GH2OAGT(34-42)H2OCl-ENPEP [plasmamembrane]AGT(36-41)REN(24-406) [plasmamembrane]H2OenalaprilatACE(30-1232)H2OAGT(34-41)ATP6AP2 [plasmamembrane]captoprilH2OCMA1AGT(34-43)H2OCarboxypeptidaseH2OProrenin-ProreninReceptorH2OATP6AP2 [plasmamembrane]H2Oramiprilat15343416, 379


Description

Angiotensinogen, a prohormone, is synthesized and secreted mainly by the liver but also from other tissues (reviewed in Fyhrquist and Saijonmaa 2008, Cat and Touyz 2011). Renin, an aspartyl protease specific for angiotensinogen, is secreted into the bloodstream by juxtaglomerular cells of the kidney in response to a drop in blood pressure. Renin cleaves angiotensinogen to yield a decapaptide, angiotensin I (angiotensin-1, angiotensin-(1-10)). Circulating renin can also bind the membrane-localized (pro)renin receptor (ATP6AP2) which increases its catalytic activity. After cleavage of angiotensinogen to angiotensin I by renin, two C-terminal amino acid residues of angiotensin I are removed by angiotensin-converting enzyme (ACE), located on the surface of endothelial cells, to yield angiotensin II (angiotensin-2, angiotensin-(1-8)), the active peptide that causes vasoconstriction, resorption of sodium and chloride, excretion of potassium, water retention, and aldosterone secretion.
More recently other, more tissue-localized pathways leading to angiotensin II and alternative derivatives of angiotensinogen have been identified (reviewed in Kramkowski et al. 2006, Kumar et al. 2007, Fyhrquist and Saijonmaa 2008, Becari et al. 2011). Chymase, cathepsin G, and cathepsin X (cathepsin Z) can each cleave angiotensin I to yield angiotensin II. Angiotensin-converting enzyme 2 (ACE2) cleaves 1 amino acid residue from angiotensin I (angiotensin-(1-10)) to yield angiotensin-(1-9), which can be cleaved by ACE to yield angiotensin-(1-7). ACE2 can also cleave angiotensin II to yield angiotensin-(1-7). Neprilysin can cleave either angiotensin-(1-9) or angiotensin I to yield angiotensin-(1-7). Angiotensin-(1-7) binds the MAS receptor (MAS1, MAS proto-oncogene) and, interestingly, produces effects opposite to those produced by angiotensin II.
Aminopeptidase A (APA, ENPEP) cleaves angiotensin II to yield angiotensin III (angiotensin-(2-8)), which is then cleaved by aminopeptidase N (APN, ANPEP) yielding angiotensin IV (angiotensin-(3-8)). Angiotensin IV binds the AT4 receptor (AT4R, IRAP, LNPEP, oxytocinase).
Inhibitors of renin (e.g. aliskiren) and ACE (e.g. lisinopril, ramipril) are currently used to treat hypertension (reviewed in Gerc et al. 2009, Verdecchia et al. 2010, Alreja and Joseph 2011).Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=2022377

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Wood JM, Maibaum J, Rahuel J, Grütter MG, Cohen NC, Rasetti V, Rüger H, Göschke R, Stutz S, Fuhrer W, Schilling W, Rigollier P, Yamaguchi Y, Cumin F, Baum HP, Schnell CR, Herold P, Mah R, Jensen C, O'Brien E, Stanton A, Bedigian MP.; ''Structure-based design of aliskiren, a novel orally effective renin inhibitor.''; PubMed Europe PMC Scholia
  2. Gerc V, Buksa M, Loza V, Kulic M.; ''Is aliskiren superior to inhibitors of angiotensin-converting enzyme and angiotensin receptor blockers in renin-angiotensin system blockade?''; PubMed Europe PMC Scholia
  3. Wu C, Lu H, Cassis LA, Daugherty A.; ''Molecular and Pathophysiological Features of Angiotensinogen: A Mini Review.''; PubMed Europe PMC Scholia
  4. Fyhrquist F, Saijonmaa O.; ''Renin-angiotensin system revisited.''; PubMed Europe PMC Scholia
  5. Hayakari M, Amano K, Izumi H, Murakami S.; ''Purification of angiotensin-converting enzyme from human intestine.''; PubMed Europe PMC Scholia
  6. Alreja G, Joseph J.; ''Renin and cardiovascular disease: Worn-out path, or new direction.''; PubMed Europe PMC Scholia
  7. Crowley SD, Coffman TM.; ''Recent advances involving the renin-angiotensin system.''; PubMed Europe PMC Scholia
  8. Nägler DK, Lechner AM, Oettl A, Kozaczynska K, Scheuber HP, Gippner-Steppert C, Bogner V, Biberthaler P, Jochum M.; ''An enzyme-linked immunosorbent assay for human cathepsin X, a potential new inflammatory marker.''; PubMed Europe PMC Scholia
  9. Gossas T, Vrang L, Henderson I, Sedig S, Sahlberg C, Lindström E, Danielson UH.; ''Aliskiren displays long-lasting interactions with human renin.''; PubMed Europe PMC Scholia
  10. Grönhagen-Riska C, Fyhrquist F.; ''Purification of human lung angiotensin-converting enzyme.''; PubMed Europe PMC Scholia
  11. Baudin B, Bénéteau-Burnat B.; ''Mixed-type inhibition of pulmonary angiotensin I-converting enzyme by captopril, enalaprilat and ramiprilat.''; PubMed Europe PMC Scholia
  12. Kramkowski K, Mogielnicki A, Buczko W.; ''The physiological significance of the alternative pathways of angiotensin II production.''; PubMed Europe PMC Scholia
  13. Campbell DJ.; ''The renin-angiotensin and the kallikrein-kinin systems.''; PubMed Europe PMC Scholia
  14. Goldstein SM, Kaempfer CE, Proud D, Schwartz LB, Irani AM, Wintroub BU.; ''Detection and partial characterization of a human mast cell carboxypeptidase.''; PubMed Europe PMC Scholia
  15. Owen CA, Campbell EJ.; ''Angiotensin II generation at the cell surface of activated neutrophils: novel cathepsin G-mediated catalytic activity that is resistant to inhibition.''; PubMed Europe PMC Scholia
  16. Richard V, Hurel-Merle S, Scalbert E, Ferry G, Lallemand F, Bessou JP, Thuillez C.; ''Functional evidence for a role of vascular chymase in the production of angiotensin II in isolated human arteries.''; PubMed Europe PMC Scholia
  17. Raymond WW, Trivedi NN, Makarova A, Ray M, Craik CS, Caughey GH.; ''How immune peptidases change specificity: cathepsin G gained tryptic function but lost efficiency during primate evolution.''; PubMed Europe PMC Scholia
  18. Thomsen R, Rasmussen HB, Linnet K, INDICES Consortium.; ''In vitro drug metabolism by human carboxylesterase 1: focus on angiotensin-converting enzyme inhibitors.''; PubMed Europe PMC Scholia
  19. Haas E, Goldblatt H.; ''Kinetic constants of the human renin and human angiotensinogen reaction.''; PubMed Europe PMC Scholia
  20. Johnston CI, Jackson B, Cubela R, Larmour I, Arnolda L.; ''Evaluation of angiotensin converting enzyme (ACE) in the pharmacokinetics and pharmacodynamics of ACE inhibitors.''; PubMed Europe PMC Scholia
  21. Gould AB, Green D.; ''Kinetics of the human renin and human substrate reaction.''; PubMed Europe PMC Scholia
  22. Díaz-Perales A, Quesada V, Sánchez LM, Ugalde AP, Suárez MF, Fueyo A, López-Otín C.; ''Identification of human aminopeptidase O, a novel metalloprotease with structural similarity to aminopeptidase B and leukotriene A4 hydrolase.''; PubMed Europe PMC Scholia
  23. Kumar R, Singh VP, Baker KM.; ''The intracellular renin-angiotensin system: a new paradigm.''; PubMed Europe PMC Scholia
  24. Rosenthal J, Wolff HP, Weber P, Dahlheim H.; ''Enzyme kinetic studies on human renin and its purified homologous substrate.''; PubMed Europe PMC Scholia
  25. Verdecchia P, Angeli F, Mazzotta G, Martire P, Garofoli M, Gentile G, Reboldi G.; ''Aliskiren versus ramipril in hypertension.''; PubMed Europe PMC Scholia
  26. Nguyen Dinh Cat A, Touyz RM.; ''A new look at the renin-angiotensin system--focusing on the vascular system.''; PubMed Europe PMC Scholia
  27. Axton R, Wallis JA, Taylor H, Hanks M, Forrester LM.; ''Aminopeptidase O contains a functional nucleolar localization signal and is implicated in vascular biology.''; PubMed Europe PMC Scholia
  28. Lechner AM, Assfalg-Machleidt I, Zahler S, Stoeckelhuber M, Machleidt W, Jochum M, Nägler DK.; ''RGD-dependent binding of procathepsin X to integrin alphavbeta3 mediates cell-adhesive properties.''; PubMed Europe PMC Scholia
  29. Ehlers MR, Kirsch RE.; ''Catalysis of angiotensin I hydrolysis by human angiotensin-converting enzyme: effect of chloride and pH.''; PubMed Europe PMC Scholia
  30. Ehlers MR, Chen YN, Riordan JF.; ''Purification and characterization of recombinant human testis angiotensin-converting enzyme expressed in Chinese hamster ovary cells.''; PubMed Europe PMC Scholia
  31. Kono T, Ikeda F, Oseko F, Imura H, Endo J.; ''Effects of angiotensin I-converting enzyme inhibitor, SQ 14225, in nomal men.''; PubMed Europe PMC Scholia
  32. Ehlers MR, Maeder DL, Kirsch RE.; ''Rapid affinity chromatographic purification of human lung and kidney angiotensin-converting enzyme with the novel N-carboxyalkyl dipeptide inhibitor N-[1(S)-carboxy-5-aminopentyl]glycylglycine.''; PubMed Europe PMC Scholia
  33. Brzezinski MR, Abraham TL, Stone CL, Dean RA, Bosron WF.; ''Purification and characterization of a human liver cocaine carboxylesterase that catalyzes the production of benzoylecgonine and the formation of cocaethylene from alcohol and cocaine.''; PubMed Europe PMC Scholia
  34. Nägler DK, Kraus S, Feierler J, Mentele R, Lottspeich F, Jochum M, Faussner A.; ''A cysteine-type carboxypeptidase, cathepsin X, generates peptide receptor agonists.''; PubMed Europe PMC Scholia
  35. Goto Y, Hattori A, Ishii Y, Mizutani S, Tsujimoto M.; ''Enzymatic properties of human aminopeptidase A. Regulation of its enzymatic activity by calcium and angiotensin IV.''; PubMed Europe PMC Scholia
  36. Stewart TA, Weare JA, Erdös EG.; ''Purification and characterization of human converting enzyme (kininase II).''; PubMed Europe PMC Scholia
  37. Urata H, Kinoshita A, Misono KS, Bumpus FM, Husain A.; ''Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart.''; PubMed Europe PMC Scholia
  38. Becari C, Oliveira EB, Salgado MC.; ''Alternative pathways for angiotensin II generation in the cardiovascular system.''; PubMed Europe PMC Scholia
  39. Kono T, Oseko F, Ikeda F, Nakano R, Taniguchi A, Imura H, Endo J.; ''Effects of a new angiotensin-converting enzyme inhibitor, MK 421, in normal men and patients.''; PubMed Europe PMC Scholia
  40. Tokioka-Terao M, Hiwada K, Kokubu T.; ''Purification and characterization of aminopeptidase N from human plasma.''; PubMed Europe PMC Scholia
  41. Favre L, Vallotton MB.; ''Kinetics of the reaction of human renin with natural substrates and tetradecapeptide substrate.''; PubMed Europe PMC Scholia
  42. Caughey GH, Raymond WW, Wolters PJ.; ''Angiotensin II generation by mast cell alpha- and beta-chymases.''; PubMed Europe PMC Scholia
  43. Reilly CF, Tewksbury DA, Schechter NM, Travis J.; ''Rapid conversion of angiotensin I to angiotensin II by neutrophil and mast cell proteinases.''; PubMed Europe PMC Scholia
  44. Wei L, Alhenc-Gelas F, Soubrier F, Michaud A, Corvol P, Clauser E.; ''Expression and characterization of recombinant human angiotensin I-converting enzyme. Evidence for a C-terminal transmembrane anchor and for a proteolytic processing of the secreted recombinant and plasma enzymes.''; PubMed Europe PMC Scholia
  45. Rice GI, Thomas DA, Grant PJ, Turner AJ, Hooper NM.; ''Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism.''; PubMed Europe PMC Scholia
  46. Campbell EJ, Silverman EK, Campbell MA.; ''Elastase and cathepsin G of human monocytes. Quantification of cellular content, release in response to stimuli, and heterogeneity in elastase-mediated proteolytic activity.''; PubMed Europe PMC Scholia
  47. Wei L, Alhenc-Gelas F, Corvol P, Clauser E.; ''The two homologous domains of human angiotensin I-converting enzyme are both catalytically active.''; PubMed Europe PMC Scholia
  48. Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ.; ''A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase.''; PubMed Europe PMC Scholia
  49. Vickers C, Hales P, Kaushik V, Dick L, Gavin J, Tang J, Godbout K, Parsons T, Baronas E, Hsieh F, Acton S, Patane M, Nichols A, Tummino P.; ''Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase.''; PubMed Europe PMC Scholia
  50. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S.; ''A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9.''; PubMed Europe PMC Scholia
  51. Nguyen G, Delarue F, Burcklé C, Bouzhir L, Giller T, Sraer JD.; ''Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin.''; PubMed Europe PMC Scholia
  52. Natesh R, Schwager SL, Sturrock ED, Acharya KR.; ''Crystal structure of the human angiotensin-converting enzyme-lisinopril complex.''; PubMed Europe PMC Scholia
  53. Pindel EV, Kedishvili NY, Abraham TL, Brzezinski MR, Zhang J, Dean RA, Bosron WF.; ''Purification and cloning of a broad substrate specificity human liver carboxylesterase that catalyzes the hydrolysis of cocaine and heroin.''; PubMed Europe PMC Scholia
  54. Goldstein SM, Kaempfer CE, Kealey JT, Wintroub BU.; ''Human mast cell carboxypeptidase. Purification and characterization.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
117777view13:59, 22 May 2021EweitzModified title
114755view16:24, 25 January 2021ReactomeTeamReactome version 75
113199view11:26, 2 November 2020ReactomeTeamReactome version 74
112889view13:25, 15 October 2020Fehrhartfixed screwed up complex graphics for this version
112424view15:36, 9 October 2020ReactomeTeamReactome version 73
101328view11:21, 1 November 2018ReactomeTeamreactome version 66
100866view20:54, 31 October 2018ReactomeTeamreactome version 65
100407view19:28, 31 October 2018ReactomeTeamreactome version 64
99955view16:12, 31 October 2018ReactomeTeamreactome version 63
99511view14:45, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93849view13:40, 16 August 2017ReactomeTeamreactome version 61
93407view11:22, 9 August 2017ReactomeTeamreactome version 61
87886view12:24, 25 July 2016RyanmillerOntology Term : 'peptide and protein metabolic process' added !
87885view12:23, 25 July 2016RyanmillerOntology Term : 'classic metabolic pathway' added !
86495view09:19, 11 July 2016ReactomeTeamreactome version 56
83131view10:04, 18 November 2015ReactomeTeamVersion54
81474view13:00, 21 August 2015ReactomeTeamVersion53
81167view14:08, 29 July 2015EgonwFixed the data source name.
76948view08:22, 17 July 2014ReactomeTeamFixed remaining interactions
76653view12:02, 16 July 2014ReactomeTeamFixed remaining interactions
75982view10:04, 11 June 2014ReactomeTeamRe-fixing comment source
75685view11:01, 10 June 2014ReactomeTeamReactome 48 Update
75041view13:55, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74685view08:45, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ACE(30-1232)ProteinP12821 (Uniprot-TrEMBL)
ACE(30-1306)ProteinP12821 (Uniprot-TrEMBL)
ACE2(18-805)ProteinQ9BYF1 (Uniprot-TrEMBL)
AGT(34-40)ProteinP01019 (Uniprot-TrEMBL)
AGT(34-41)ProteinP01019 (Uniprot-TrEMBL)
AGT(34-42)ProteinP01019 (Uniprot-TrEMBL)
AGT(34-43)ProteinP01019 (Uniprot-TrEMBL)
AGT(35-41)ProteinP01019 (Uniprot-TrEMBL)
AGT(36-41)ProteinP01019 (Uniprot-TrEMBL)
AGTProteinP01019 (Uniprot-TrEMBL)
ANPEP DimerComplexREACT_148325 (Reactome)
ANPEP [plasma membrane]ProteinP15144 (Uniprot-TrEMBL)
ATP6AP2 [plasma membrane]ProteinO75787 (Uniprot-TrEMBL)
CMA1ProteinP23946 (Uniprot-TrEMBL)
CTSZProteinQ9UBR2 (Uniprot-TrEMBL) After secretion Cathepsin Z (Cathepsin X) is extracellular and associated with the plasma membrane.
CarboxypeptidaseProteinREACT_164275 (Reactome) This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
Cathepsin GProteinREACT_161260 (Reactome) This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
Cl-MetaboliteCHEBI:17996 (ChEBI)
ENPEP DimerComplexREACT_148271 (Reactome)
ENPEP [plasma membrane]ProteinQ07075 (Uniprot-TrEMBL)
H2OMetaboliteCHEBI:15377 (ChEBI)
MMEProteinP08473 (Uniprot-TrEMBL)
Prorenin-Prorenin ReceptorComplexREACT_148518 (Reactome)
REN(24-406) [plasma membrane]ProteinP00797 (Uniprot-TrEMBL)
Renin:Prorenin ReceptorComplexREACT_148206 (Reactome)
ReninProteinREACT_160942 (Reactome) This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
aliskirenMetaboliteCHEBI:601027 (ChEBI)
captoprilMetaboliteCHEBI:3380 (ChEBI)
enalaprilatMetaboliteCHEBI:4786 (ChEBI)
lisinoprilMetaboliteCHEBI:43755 (ChEBI)
ramiprilatMetabolite5464096 (PubChem Compound)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ACE(30-1232)mim-catalysisREACT_147705 (Reactome)
ACE(30-1306)mim-catalysisREACT_147747 (Reactome)
ACE(30-1306)mim-catalysisREACT_147855 (Reactome)
ACE2(18-805)mim-catalysisREACT_147733 (Reactome)
ACE2(18-805)mim-catalysisREACT_147889 (Reactome)
AGT(34-40)ArrowREACT_147762 (Reactome)
AGT(34-40)ArrowREACT_147787 (Reactome)
AGT(34-40)ArrowREACT_147855 (Reactome)
AGT(34-40)ArrowREACT_147889 (Reactome)
AGT(34-41)ArrowREACT_147705 (Reactome)
AGT(34-41)ArrowREACT_147744 (Reactome)
AGT(34-41)ArrowREACT_147747 (Reactome)
AGT(34-41)ArrowREACT_147760 (Reactome)
AGT(34-41)ArrowREACT_147799 (Reactome)
AGT(34-41)REACT_147872 (Reactome)
AGT(34-41)REACT_147889 (Reactome)
AGT(34-42)ArrowREACT_147733 (Reactome)
AGT(34-42)ArrowREACT_147882 (Reactome)
AGT(34-42)REACT_147762 (Reactome)
AGT(34-42)REACT_147855 (Reactome)
AGT(34-43)ArrowREACT_147720 (Reactome)
AGT(34-43)ArrowREACT_147869 (Reactome)
AGT(34-43)ArrowREACT_147891 (Reactome)
AGT(34-43)REACT_147705 (Reactome)
AGT(34-43)REACT_147733 (Reactome)
AGT(34-43)REACT_147744 (Reactome)
AGT(34-43)REACT_147747 (Reactome)
AGT(34-43)REACT_147760 (Reactome)
AGT(34-43)REACT_147787 (Reactome)
AGT(34-43)REACT_147799 (Reactome)
AGT(34-43)REACT_147882 (Reactome)
AGT(35-41)ArrowREACT_147872 (Reactome)
AGT(35-41)REACT_147767 (Reactome)
AGT(36-41)ArrowREACT_147767 (Reactome)
AGTREACT_147720 (Reactome)
AGTREACT_147869 (Reactome)
AGTREACT_147891 (Reactome)
ANPEP Dimermim-catalysisREACT_147767 (Reactome)
CMA1mim-catalysisREACT_147760 (Reactome)
CTSZmim-catalysisREACT_147799 (Reactome)
Carboxypeptidasemim-catalysisREACT_147882 (Reactome)
Cathepsin Gmim-catalysisREACT_147744 (Reactome)
Cl-ArrowREACT_147705 (Reactome)
Cl-ArrowREACT_147747 (Reactome)
ENPEP Dimermim-catalysisREACT_147872 (Reactome)
H2OREACT_147705 (Reactome)
H2OREACT_147720 (Reactome)
H2OREACT_147733 (Reactome)
H2OREACT_147744 (Reactome)
H2OREACT_147747 (Reactome)
H2OREACT_147760 (Reactome)
H2OREACT_147762 (Reactome)
H2OREACT_147767 (Reactome)
H2OREACT_147787 (Reactome)
H2OREACT_147799 (Reactome)
H2OREACT_147855 (Reactome)
H2OREACT_147869 (Reactome)
H2OREACT_147872 (Reactome)
H2OREACT_147882 (Reactome)
H2OREACT_147889 (Reactome)
H2OREACT_147891 (Reactome)
MMEmim-catalysisREACT_147762 (Reactome)
MMEmim-catalysisREACT_147787 (Reactome)
Prorenin-Prorenin Receptormim-catalysisREACT_147720 (Reactome)
REACT_147705 (Reactome) Secreted angiotensin-converting enzyme (ACE) cleaves 2 amino acid residues from the C-terminus of angiotensin-(1-10) (angiotensin I) to yield angiotensin-(1-8) (angiotensin II) (Wei et al. 1991). This reaction is inhibited by drugs used to treat hypertension (angiotensin converting enzyme inhibitors, ACEI) including captopril (Gronhagen-Riska and Fyhrquist 1980, Stewart et al. 1981, Ehlers et al. 1986, Hayakari et al. 1989, Wei et al. 1991, Baudin and Beneteau-Burnat 1999), enalaprilat (metablized from the prodrug enalapril, Wei et al. 1991, Baudin and Beneteau-Burnat 1999), lisinopril ( Ehlers et al. 1991, Natesh et al. 2003), and ramiprilat (metabolized from the prodrug ramipril, Baudin and Beneteau-Burnat 1999). ACE is secreted ("shed") from membranes of endothelial cells by cleavage in the C-terminal region that removes the membrane anchor.
REACT_147720 (Reactome) The binding of prorenin to the (pro)renin receptor activates the protease activity of prorenin, which can then hydrolyze angiotensinogen to yield angiotensin-(1-10) (angiotensin I) (Nguyen et al. 2002). Prorenin is inactive when not bound to the (pro)renin receptor. Aliskiren, a drug used clinically to treat hypertension, inhibits the cleavage of angiotensinogen by renin (Gossas et al. 2011, Wood et al. 2003, reviewed in Gerc et al. 2009).
REACT_147733 (Reactome) Angiotensin-converting enzyme 2 (ACE2) hydrolyzes angiotensin-(1-10) (angiotensin I) to yield angiotensin-(1-9) (Donoghue et al. 2000, Tipnis et al. 2000, Vickers et al. 2002, Rice t al. 2004). The activity of ACE2 on angiotensin I is weak (Rice et al. 2004), being 400-fold lower than the activity of ACE2 on angiotensin II (Vickers et al. 2002).
REACT_147744 (Reactome) Cathepsin G hydrolyzes angiotensin-(1-10) (angiotensin I) to yield angiotensin-(1-8) (angiotensin II) (Reilly et al. 1982, Owen and Campbell 1998, Raymond et al. 2010). Cathepsin bound to the plasma membrane of neutrophils has a higher activity than does soluble cathepsin G (Owen and Campbell 1998).
REACT_147747 (Reactome) Angiotensin-converting enzyme (ACE) hydrolyzes angiotensin-(1-10) (angiotensin I) to yield angiotensin-(1-8) (angiotensin II) (Ehlers and Kirsch 1988). ACE is found at the plasma membrane of endothelial cells. This reaction is inhibited by drugs used to treat hypertension (angiotensin converting enzyme inhibitors, ACEI) including captopril (Gronhagen-Riska and Fyhrquist 1980, Stewart et al. 1981, Ehlers et al. 1986, Hayakari et al. 1989, Wei et al. 1991, Baudin and Beneteau-Burnat 1999), enalaprilat (metablized from the prodrug enalapril, Wei et al. 1991, Baudin and Beneteau-Burnat 1999), lisinopril ( Ehlers et al. 1991, Natesh et al. 2003), and ramiprilat (metabolized from the prodrug ramipril, Baudin and Beneteau-Burnat 1999).
REACT_147760 (Reactome) Chymase hydrolyzes angiotensin-(1-10) (angiotensin) to yield angiotensin-(1-8) (angiotensin II) at a higher rate than does angiotensin-converting enzyme (Reilly et al. 1982, Urata et al. 1990, Caughey et al. 2000, Richard et al. 2001).
REACT_147762 (Reactome) Neprilysin hydrolyzes angiotensin-(1-9) to yield angiotensin-(1-7) (Rice et al. 2004). The hydrolysis of angiotensin-(1-9) catalyzed by neprilysin is more efficient than that catalyzed by angiotensin-converting enzyme (ACE) (Rice et al. 2004).
REACT_147767 (Reactome) Aminopeptidase N (APN, ANPEP, aminopeptidase M, alanyl aminopeptidase) hydrolyzes angiotensin-(2-8) (angiotensin III) to yield angiotensin-(3-8) (angiotensin IV) (see the positive control reactions in Diaz-Perales et al. 2005). Aminopeptidase O (AOPEP) also hydrolyzes angiotensin-(2-8) to angiotensin-(3-8) in vitro (Diaz-Perales et al. 2005) but AOPEP is located in the nucleolus in vivo (Axton et al. 2008) and angiotensin-(2-8) has not been observed in the nucleus.
REACT_147787 (Reactome) Neprilysin hydrolyzes angiotensin-(1-10) (angiotensin I) directly to angiotensin-(1-7) (Rice et al. 2004).
REACT_147799 (Reactome) Cathepsin Z (cathepsin X) hydrolyzes angiotensin-(1-10) (angiotensin I) to yield angiotensin-(1-8) (angiotensin II) (Nagler et al. 2010).
REACT_147855 (Reactome) Angiotensin-converting enzyme (ACE) hydrolyzes angiotensin-(1-9) to yield angiotensin-(1-7) (Rice et al. 2004).
REACT_147869 (Reactome) Renin in the bloodstream hydrolyzes angiotensinogen to yield angiotensin-(1-10) (angiotensin I). Renin is produced in the juxtaglomerular cells of the kidney in response to reduced blood pressure. Aliskiren, a drug used clinically to treat hypertension, inhibits this reaction (Gossas et al. 2011, Wood et al. 2003, reviewed in Gerc et al. 2009).
REACT_147872 (Reactome) Aminopeptidase A (APA, ENPEP) hydrolyzes the N-terminal amino acid of angiotensin-(1-8) (angiotensin II) to yield angiotensin-(2-8) (angiotensin III) (Goto et al. 2006). The catalysis is more specific and efficient in the presence of calcium ions (Goto et al. 2006).
REACT_147882 (Reactome) Mast cell carboxypeptidase (CPA3) hydrolyzes a single amino acid residue from the C-terminus of angiotensin-(1-10) (angiotensin I) to yield angiotensin-(1-9).
REACT_147889 (Reactome) Angiotensin-converting enzyme 2 (ACE2) hydrolyzes angiotensin-(1-8) (angiotensin II) to yield angiotensin-(1-7) (Vickers et al. 2002, Rice et al. 2004). The activity of ACE2 on angiotensin-(1-8) is 400-fold higher than on angiotensin-(1-10) (Vickers et al. 2002).
REACT_147891 (Reactome) Renin bound to the (pro)renin receptor (ATP6AP2) hydrolyzes angiotensinogen to yield angiotensin-(1-10) (angiotensin I) (Nguyen et al. 2002). Binding to the (pro)renin receptor increases the catalytic efficiency of renin 4-fold (Nguyen et al. 2002). Aliskiren, a drug used clinically to treat hypertension, inhibits cleavage of angiotensinogen by renin (Gossas et al. 2011, Wood et al. 2003, reviewed in Gerc et al. 2009).
Renin:Prorenin ReceptorArrowREACT_147891 (Reactome)
Renin:Prorenin Receptormim-catalysisREACT_147891 (Reactome)
Reninmim-catalysisREACT_147869 (Reactome)
aliskirenTBarREACT_147720 (Reactome)
aliskirenTBarREACT_147869 (Reactome)
aliskirenTBarREACT_147891 (Reactome)
captoprilTBarREACT_147705 (Reactome)
captoprilTBarREACT_147747 (Reactome)
enalaprilatTBarREACT_147705 (Reactome)
enalaprilatTBarREACT_147747 (Reactome)
lisinoprilTBarREACT_147705 (Reactome)
lisinoprilTBarREACT_147747 (Reactome)
ramiprilatTBarREACT_147705 (Reactome)
ramiprilatTBarREACT_147747 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP2729"
Personal tools