ACE inhibitor pathway (Homo sapiens)

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299EDHFMesangial cells aroundblood vessels in the kidneysZona glomerulosa of the adrenal glandBlood vesselsCYP11B2ACE23TGFB110ACE7NOS3AGTR29TFsNR3C2KNG13, 4BradykininMAS1REN10BDKRB2CMA1ACECTSG6BDKRB1Ang 1-9Ang 1-7Angiotensin IIAGTACE inhibitorDeoxycorticosteroneAldosteroneAngiotensin I3AGTR1Ca2+ProstacyclinATP6AP2TFs8Ang 1-5ACEACE2


The core of this pathway was elucidated over a century ago and involves the conversion of angiotensinogen to angiotensin I (Ang I) by renin, its subsequent conversion to angiotensin II (Ang II) by angiotensin converting enzyme. Ang II activates the angiotensin II receptor type 1 to induce aldosterone synthesis, increasing water and salt resorption and potassium excretion in the kidney and increasing blood pressure.

Source: PharmGKB (

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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  1. Athyros VG, Mikhailidis DP, Kakafika AI, Tziomalos K, Karagiannis A; ''Angiotensin II reactivation and aldosterone escape phenomena in renin-angiotensin-aldosterone system blockade: is oral renin inhibition the solution?''; Expert Opin Pharmacother, 2007 PubMed Europe PMC Scholia
  2. Hamming I, Cooper ME, Haagmans BL, Hooper NM, Korstanje R, Osterhaus AD, Timens W, Turner AJ, Navis G, van Goor H; ''The emerging role of ACE2 in physiology and disease.''; J Pathol, 2007 PubMed Europe PMC Scholia
  3. Bassett MH, White PC, Rainey WE; ''The regulation of aldosterone synthase expression.''; Mol Cell Endocrinol, 2004 PubMed Europe PMC Scholia
  4. Maron BA, Leopold JA; ''Mineralocorticoid receptor antagonists and endothelial function.''; Curr Opin Investig Drugs, 2008 PubMed Europe PMC Scholia
  5. McDowell SE, Coleman JJ, Ferner RE; ''Systematic review and meta-analysis of ethnic differences in risks of adverse reactions to drugs used in cardiovascular medicine.''; BMJ, 2006 PubMed Europe PMC Scholia
  6. Schwartz GL, Turner ST; ''Pharmacogenetics of antihypertensive drug responses.''; Am J Pharmacogenomics, 2004 PubMed Europe PMC Scholia
  7. Huang Y, Wongamorntham S, Kasting J, McQuillan D, Owens RT, Yu L, Noble NA, Border W; ''Renin increases mesangial cell transforming growth factor-beta1 and matrix proteins through receptor-mediated, angiotensin II-independent mechanisms.''; Kidney Int, 2006 PubMed Europe PMC Scholia
  8. Batenburg WW, Jan Danser AH; ''The (pro)renin receptor: a new addition to the renin-angiotensin system?''; Eur J Pharmacol, 2008 PubMed Europe PMC Scholia
  9. Weir MR; ''Effects of renin-angiotensin system inhibition on end-organ protection: can we do better?''; Clin Ther, 2007 PubMed Europe PMC Scholia
  10. Ferreira AJ, Raizada MK; ''Are we poised to target ACE2 for the next generation of antihypertensives?''; J Mol Med, 2008 PubMed Europe PMC Scholia


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128561view00:59, 13 February 2024EweitzDecrease font size of cell label
128560view00:56, 13 February 2024EweitzRefine Ca++ to Ca2+, economize layout
128071view00:37, 24 January 2024EweitzStandardize case
126205view21:57, 14 April 2023Khanspersdata node order
121084view14:28, 7 February 2022MkutmonOntology Term : 'signaling pathway' added !
118788view21:53, 1 June 2021EweitzOntology Term : 'mesangial cell' added !
116804view10:09, 14 May 2021EweitzModified title
107642view18:06, 24 October 2019Khanspers
107377view22:24, 2 October 2019AlexanderPicoOntology Term : 'hypertension' added !
106817view13:29, 17 September 2019MaintBotHMDB identifier normalization
105866view23:28, 15 August 2019KhanspersModified description
105430view04:30, 8 August 2019KhanspersModified description
96328view09:32, 8 March 2018Mkutmonremove old WP category
96005view09:35, 15 February 2018DeSlRemoved licence number
96004view09:33, 15 February 2018DeSlChanged MIM conversion between gene and metabolite to arrow.
92084view18:10, 24 April 2017KhanspersReverted to version '18:16, 17 February 2016' by Khanspers
92083view18:10, 24 April 2017Khansperstest
92082view18:09, 24 April 2017Khanspersmoved node
84372view18:16, 17 February 2016AlexanderPicoReverted to version '04:16, 15 October 2014' by AlexanderPico
84290view21:56, 3 February 2016AlexanderPicoQuick edit to datanode annotation or property
77712view11:16, 15 October 2014EgonwAdded KEGG IDs for ang (1-5) and and (1-7).
77711view11:04, 15 October 2014EgonwAdded a ChemSpider ID for "Ang 1-7".
77710view10:47, 15 October 2014EgonwRemoved a spuruous char from the label, improving the vertical centering.
70881view22:01, 12 September 2013MaintBotReverted to version '13:01, 5 September 2013' by MaintBot
70859view12:13, 12 September 2013NunoModified description
70755view13:01, 5 September 2013EgonwAdded a ChEBI id for 'ACE inhibitor'.
67020view09:55, 26 June 2013Christine ChichesterOntology Term : 'ACE inhibitor drug pathway' added !
63137view19:14, 8 May 2013MaintBotUpdating GPML version
57086view20:47, 20 January 2013EgonwAdded missing PubChem-compound data source.
48249view06:21, 17 May 2012MaintBotUpdating PubChem xrefs
44938view12:24, 6 October 2011MartijnVanIerselOntology Term : 'angiotensin signaling pathway' added !
41083view23:20, 1 March 2011MaintBotRemoved redundant pathway information and comments
39013view19:32, 27 September 2010AlexanderPico
39012view19:31, 27 September 2010AlexanderPicoModified description
39011view19:30, 27 September 2010AlexanderPicoadded detail and clarified interactions
38918view21:05, 24 September 2010Khanspers
38365view23:44, 2 September 2010KhanspersNew version uploaded
34805view23:49, 20 January 2010KhanspersModified description
34804view23:49, 20 January 2010KhanspersDeleted reference
34803view23:43, 20 January 2010KhanspersModified description
34802view23:41, 20 January 2010KhanspersDeleted reference
34801view23:30, 20 January 2010KhanspersPeriodical save, work in progress
34800view23:18, 20 January 2010KhanspersAdded citation
34799view23:18, 20 January 2010KhanspersChanged comments
34798view23:16, 20 January 2010KhanspersModified description
32148view14:00, 14 August 2009MaintBotFixed group labels
30178view20:31, 7 July 2009KhanspersAdded xref for angiotensinII
22578view13:30, 14 November 2008Thomasremoved redundant organism name after title
21846view11:32, 14 November 2008MaintBot[[Pathway:Homo sapiens:ACE-Inhibitor pathway PharmGKB]] moved to [[Pathway:WP554]]: Moved to stable identifier
14510view01:16, 23 May 2008AlexanderPicoConnected, grouped and fixed metabolites

External references


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NameTypeDatabase referenceComment
ACE inhibitorMetaboliteCHEBI:35457 (ChEBI)
ACEGeneProduct1636 (Entrez Gene)
ACE2GeneProduct59272 (Entrez Gene)
AGTGeneProduct183 (Entrez Gene)
AGTR1GeneProduct185 (Entrez Gene)
AGTR2GeneProduct186 (Entrez Gene)
ATP6AP2GeneProduct10159 (Entrez Gene)
AldosteroneMetaboliteHMDB0000037 (HMDB)
Ang 1-5MetaboliteC15852 (KEGG Compound)
Ang 1-7Metabolite110354 (Chemspider)
Ang 1-9MetaboliteC15851 (KEGG Compound)
Angiotensin IMetabolite3081372 (PubChem-compound)
Angiotensin IIMetaboliteHMDB0001035 (HMDB)
BDKRB1GeneProduct623 (Entrez Gene)
BDKRB2GeneProduct624 (Entrez Gene)
BradykininMetaboliteHMDB0004246 (HMDB)
CMA1GeneProduct1215 (Entrez Gene)
CTSGGeneProduct1511 (Entrez Gene)
CYP11B2GeneProduct1585 (Entrez Gene)
Ca2+MetaboliteHMDB0000464 (HMDB)
DeoxycorticosteroneMetaboliteHMDB0000016 (HMDB)
KNG1GeneProduct3827 (Entrez Gene)
MAS1GeneProduct4142 (Entrez Gene)
NOS3GeneProduct4846 (Entrez Gene)
NR3C2GeneProduct4306 (Entrez Gene)
ProstacyclinMetabolite114805 (PubChem-compound)
RENGeneProduct5972 (Entrez Gene)
TGFB1GeneProduct7040 (Entrez Gene)

Annotated Interactions

No annotated interactions

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