KEGG PATHWAY: ko04614

PATHWAY: ko04614

Entry

ko04614                     Pathway

Name

Renin-angiotensin system

Description

The renin-angiotensin system (RAS) is a peptidergic system with endocrine characteristics regarding to the regulation of the blood pressure and hydro-electrolytic balance. In the classical RAS, the enzyme renin cleaves its substrate angiotensinogen (Agt) forming the decapeptide angiotensin I that is in turn cleaved by angiotensin-converting enzyme (ACE) to produce the angiotensin II (Ang II), a key player of this system. Ang II activates its AT1 receptor (AT1R), the principal receptor that mediates the majority of the known actions of Ang II in the kidney, including vasoconstriction, renal sodium (Na+) reabsorption, and aldosterone secretion, increasing blood pressure and contributing to the development of hypertension. In addition to (ACE)/Ang II/AT1R and AT2R axis, other signaling pathways in the RAS, such as ACE2/angiotensin-(1-7)/Mas and Ang IV/IRAP, and other active peptide of the RAS, with physiological relevance as Ang III, Ang A and alamandine, are now widely recognized.

Class

Organismal Systems; Endocrine system

Pathway map

ko04614

Renin-angiotensin system

Other DBs

GO:

0002003

Orthology

K09821

angiotensinogen

K01380

renin [EC:3.4.23.15]

K01283

peptidyl-dipeptidase A [EC:3.4.15.1]

K01329

chymase [EC:3.4.21.39]

K01319

cathepsin G [EC:3.4.21.20]

K01325

tissue kallikrein [EC:3.4.21.35]

K11141

glutamyl aminopeptidase [EC:3.4.11.7]

K11140

aminopeptidase N [EC:3.4.11.2]

K01322

prolyl oligopeptidase [EC:3.4.21.26]

K09708

angiotensin-converting enzyme 2 [EC:3.4.17.23]

K13289

cathepsin A (carboxypeptidase C) [EC:3.4.16.5]

K08780

carboxypeptidase A3 [EC:3.4.17.1]

K01389

neprilysin [EC:3.4.24.11]

K01392

thimet oligopeptidase [EC:3.4.24.15]

K01393

neurolysin [EC:3.4.24.16]

K01285

lysosomal Pro-X carboxypeptidase [EC:3.4.16.2]

K04303

proto-oncogene Mas

K08392

Mas-related G protein-coupled receptor member D

K04166

angiotensin II receptor type 1

K04167

angiotensin II receptor type 2

K01257

cystinyl aminopeptidase [EC:3.4.11.3]

K19514

renin receptor

Compound

C00873

Angiotensin I

C02135

Angiotensin II

C15848

Angiotensin III

C15849

Angiotensin IV

C15850

Angiotensin (1-7)

C15851

Angiotensin (1-9)

C15852

Angiotensin (1-5)

C20970

Angiotensin A

C20971

Alamandine

C20972

Angiotensin (5-8)

C20973

Angiotensin (5-7)

Reference

PMID:17229979

Authors

Kramkowski K, Mogielnicki A, Buczko W.

Title

The physiological significance of the alternative pathways of angiotensin II production.

Journal

J Physiol Pharmacol 57:529-39 (2006)

Reference

PMID:15549172

Authors

Danilczyk U, Eriksson U, Oudit GY, Penninger JM.

Title

Physiological roles of angiotensin-converting enzyme 2.

Journal

Cell Mol Life Sci 61:2714-9 (2004)
DOI:10.1007/s00018-004-4241-6

Reference

PMID:15549171

Authors

Warner FJ, Smith AI, Hooper NM, Turner AJ.

Title

Angiotensin-converting enzyme-2: a molecular and cellular perspective.

Journal

Cell Mol Life Sci 61:2704-13 (2004)
DOI:10.1007/s00018-004-4240-7

Reference

PMID:15833268

Authors

Kurdi M, De Mello WC, Booz GW.

Title

Working outside the system: an update on the unconventional behavior of the renin-angiotensin system components.

Journal

Int J Biochem Cell Biol 37:1357-67 (2005)
DOI:10.1016/j.biocel.2005.01.012

Reference

PMID:15109615

Authors

Burrell LM, Johnston CI, Tikellis C, Cooper ME.

Title

ACE2, a new regulator of the renin-angiotensin system.

Journal

Trends Endocrinol Metab 15:166-9 (2004)
DOI:10.1016/j.tem.2004.03.001

Reference

PMID:16555051

Authors

von Bohlen und Halbach O, Albrecht D.

Title

The CNS renin-angiotensin system.

Journal

Cell Tissue Res 326:599-616 (2006)
DOI:10.1007/s00441-006-0190-8

Reference

PMID:12793984

Authors

Schmaier AH

Title

The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction.

Journal

Am J Physiol Regul Integr Comp Physiol 285:R1-13 (2003)
DOI:10.1152/ajpregu.00535.2002

Reference

PMID:12419208

Authors

Eriksson U, Danilczyk U, Penninger JM.

Title

Just the beginning: novel functions for angiotensin-converting enzymes.

Journal

Curr Biol 12:R745-52 (2002)
DOI:10.1016/S0960-9822(02)01255-1

Reference

PMID:16286563

Authors

Dielis AW, Smid M, Spronk HM, Hamulyak K, Kroon AA, ten Cate H, de Leeuw PW.

Title

The prothrombotic paradox of hypertension: role of the renin-angiotensin and kallikrein-kinin systems.

Journal

Hypertension 46:1236-42 (2005)
DOI:10.1161/01.HYP.0000193538.20705.23

Reference

PMID:16581295

Authors

Kuba K, Imai Y, Penninger JM.

Title

Angiotensin-converting enzyme 2 in lung diseases.

Journal

Curr Opin Pharmacol 6:271-6 (2006)
DOI:10.1016/j.coph.2006.03.001

Reference

PMID:12505055

Authors

Erdos EG, Jackman HL, Brovkovych V, Tan F, Deddish PA.

Title

Products of angiotensin I hydrolysis by human cardiac enzymes potentiate bradykinin.

Journal

J Mol Cell Cardiol 34:1569-76 (2002)
DOI:10.1006/jmcc.2002.2080

Reference

PMID:12372844

Authors

Shrimpton CN, Smith AI, Lew RA.

Title

Soluble metalloendopeptidases and neuroendocrine signaling.

Journal

Endocr Rev 23:647-64 (2002)
DOI:10.1210/er.2001-0032

Reference

PMID:12019279

Authors

Jackman HL, Massad MG, Sekosan M, Tan F, Brovkovych V, Marcic BM, Erdos EG.

Title

Angiotensin 1-9 and 1-7 release in human heart: role of cathepsin A.

Journal

Hypertension 39:976-81 (2002)
DOI:10.1161/01.HYP.0000017283.67962.02

Reference

PMID:15173164

Authors

Lundequist A, Tchougounova E, Abrink M, Pejler G.

Title

Cooperation between mast cell carboxypeptidase A and the chymase mouse mast cell protease 4 in the formation and degradation of angiotensin II.

Journal

J Biol Chem 279:32339-44 (2004)
DOI:10.1074/jbc.M405576200

Reference

PMID:17362841

Authors

Kehoe PG, Wilcock GK.

Title

Is inhibition of the renin-angiotensin system a new treatment option for Alzheimer's disease?

Journal

Lancet Neurol 6:373-8 (2007)
DOI:10.1016/S1474-4422(07)70077-7

Reference

PMID:25332897

Authors

Ferrao FM, Lara LS, Lowe J

Title

Renin-angiotensin system in the kidney: What is new?

Journal

World J Nephrol 3:64-76 (2014)
DOI:10.5527/wjn.v3.i3.64

Reference

PMID:24273531

Authors

Zhuo JL, Ferrao FM, Zheng Y, Li XC

Title

New frontiers in the intrarenal Renin-Angiotensin system: a critical review of classical and new paradigms.

Journal

Front Endocrinol (Lausanne) 4:166 (2013)
DOI:10.3389/fendo.2013.00166

Reference

PMID:21951628

Authors

Unger T, Paulis L, Sica DA

Title

Therapeutic perspectives in hypertension: novel means for renin-angiotensin-aldosterone system modulation and emerging device-based approaches.

Journal

Eur Heart J 32:2739-47 (2011)
DOI:10.1093/eurheartj/ehr253

Reference

PMID:18793332

Authors

Fyhrquist F, Saijonmaa O

Title

Renin-angiotensin system revisited.

Journal

J Intern Med 264:224-36 (2008)
DOI:10.1111/j.1365-2796.2008.01981.x

Reference

PMID:23692861

Authors

Yugandhar VG, Clark MA

Title

Angiotensin III: a physiological relevant peptide of the renin angiotensin system.

Journal

Peptides 46:26-32 (2013)
DOI:10.1016/j.peptides.2013.04.014

Reference

PMID:24760442

Authors

Etelvino GM, Peluso AA, Santos RA

Title

New components of the renin-angiotensin system: alamandine and the MAS-related G protein-coupled receptor D.

Journal

Curr Hypertens Rep 16:433 (2014)
DOI:10.1007/s11906-014-0433-0

Related
pathway

ko04270

Vascular smooth muscle contraction

ko04610

Complement and coagulation cascades

ko04924

Renin secretion

ko04925

Aldosterone synthesis and secretion

All links

Gene (22)   
   KEGG ORTHOLOGY (22)   
All databases (22)   

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