Abstract
The renin–angiotensin system (RAS) is a system of enzymes and hormones that regulate blood pressure and electrolyte and fluid homeostasis in mammals. Angiotensin II (Ang-II) is one of the most important and well-known components of RAS. It is formed from the protein precursor angiotensinogen by the sequential actions of proteolytic enzymes. The classic pathway of Ang-II generation includes a reaction catalyzed by angiotensin-converting enzyme (ACE). However, there are alternative pathways for the generation of Ang-II. In this paper, possible routes of formation of Ang-II in the human body are reviewed. Various Ang-II-generating enzymes (tonin, cathepsin G, chymase, etc.) and their properties are considered. The classification of these enzymes is also considered.
Similar content being viewed by others
REFERENCES
Goodfriend,T.L., Elliott,M.E.,and Catt,K.J.(1996) New Engl.J.Med.,334,1649-1654.
Reilly,Ch., Tewksbury,D., Schechter,N.,and Travis,J. (1982)J.Biol.Chem., 257,8619-8622.
Hollenberg,N.K., Fisher,N.D.L.,and Price,D.A. (1998)Hypertension,32,387-392.
Campbell,D.J.(1987)J.Clin.Invest.,79,1-6.
Eliseeva, Yu.E.(1998)Bioorg.Khim., 24,262-270.
Erdös E.G.,and Skidgel,R.A.(1987)Lab.Invest.,56, 345-348.
Perich,R.B., Jackson,B.,and Johnston,C.I.(1993)in The Renin-Angiotensin System,Vol.1,Biochemistry/ Physiology (Robertson,J.I.S.,and Nichols,M.G.,eds.) Gower Medical Publ., London N.Y.,pp.16-1-16-7.
Sakharov,I.Y., Dukhanina,E.A., Molokoedov,A.S., Danilov,S.M., Ovchinnikov,M.V., Bespalova,Zh.D., and Titov,M.I.(1988)Biochem.Biophys.Res.Commun.,151, 109-113.
Yang,H.Y.T., Erdös E.G.,and Levin,Y.(1970) Biochim.Biophys.Acta,214,374-376.
Eliseeva,Yu.E.,and Pavlikhina,L.V.(1974)Dokl.Akad.Nauk SSSR,217,953-956.
Unger,T.,and Gohlke,P.(1990)Am.J.Cardiol.,65,3I-10I.
Dzau,V.J.(1984)J.Cardiovasc.Pharmacol.,6 (Suppl.2), S377-S382.
Kifor,I.,and Dzau,V.J.(1987)Circ.Res.,60,422-428.
Akasu,M., Urata,H., Kinoshita,A., Sasaguri,M., Ideishi, M.,and Arakawa,K.(1998)Hypertension,32,514-520.
Dzau,V.J.(1989)J.Hypertens., 7,933-936.
Dzau, V.J.(1988)Circulation,77 (Suppl.I), I-4-I-13.
Tang,S.S., Loscalzo,J.,and Dzau,V.J.(1989)J.Vasc.Med.Biol., 1,67-74.
Wintroub,B.U., Kaempfer,C.E., Schechter,N.M.,and Proud,D.(1986)J.Clin.Invest., 77,196-201.
Kost,O.A., Ort,T.A., Nikol 'skaya, I.I., Nametkin,S.N., and Levashov,A.V.(1994)Biochemistry (Moscow),59, 1746-1755(Russ.).
Antonov,V.K.(1991)The Chemistry of Proteolysis[in Russian],Nauka, Moscow.
Corvol,P., Williams,T.A.,and Soubrier,F.(1995)Meth.Enzymol.,248,283-305.
Orth,T., Voronov,S., Binevski,P., Saenger,W.,and Kost, O.(1998)FEBS Lett.,431,255-258.
Dzau,V.J.(1993)Basic Res.Cardiol.,88 (Suppl.1),1-14.
Alhenc Gelas,F., Soubrier,F., Hubert,C.,and Corvol,P. (1990)J.Card.Pharmacol.,15 (Suppl.6),S25-S29.
Kost,O.A., Grinshtein,S.V., Nikol 'skaya, I.I., Shevchenko,A.A.,and Binevsky,P.V.(1997)Biochemistry (Moscow),62,375-383(Russ.).
Antonaccio,M.J.,and Cushman,D.W.(1981)Fed.Proc., 40,2275-2284.
Harris,R.B.,and Wilson,I.B.(1985)Int.J.Peptide Protein Res.,26,78-82.
Boucher,R., Demassieux,S., Garcia,R.,and Genest,J. (1977)Circ.Res.,41 (Suppl.II),26-29.
Klickstein,L.B., Kaempfer,C.E.,and Wintroub,B.U. (1982)J.Biol.Chem.,257,15042-15046.
Tonnesen,M., Klempner,M., Austen,K.,and Wintroub, B.(1982)J.Clin.Invest.,69,25-30.
Arakawa,K.(1996)J.Hypertens.,14 (Suppl.),S3-S7.
Belova,L.A., Ogloblina,O.G., Chykhladze,N.M., Arabidze,G.G., Kukcharchuk,V.V., Tabak 'ayn, E.V.,and Kaminnyi,A.I.(1998)in Collection of Works of Sci.Conf.“Fundamental and Applied Aspects of Modern Biochemistry ”[in Russian ],Vol.1,SPbGMU, St.Petersburg,pp.176-179.
Schwartz,M.K.,and Fleisher,M.(1970)Adv.Clin.Med., 13,114-163.
Arakawa,K., Yuki,M.,and Ikeda,M.(1980)Biochem.J., 187,647-653.
Chernukh,A.M.(1980)Inflammation[in Russian ], Meditsina, Moscow.
Barrett,A.J., Rawlings,N.D.,and Woessner,J.F.(eds.) (1998)Handbook of Proteolytic Enzymes,Academic Press, N.Y.London.
Maruta,H.,and Arakawa,K.(1983)Biochem.J., 213,193-200.
Arakawa,K.,and Maruta,H.(1980)Nature,288,705-706.
Sasaguri,M., Maeda,H., Noda,K., Tsuji,E., Kinoshita, A., Ideishi,M., Ogata,S.,and Arakawa,K.(1997)J.Hypertens.,15,675-682.
Uddin,M.,and Beg,O.U.(1995)J.Protein Chem., 14, 621-625.
Thibault,G.,and Genest,J.(1981)Biochim.Biophys.Acta, 660,23-29.
Tanaka,T., Minematsu,Y., Reilly,Ch.F., Travis,J.,and Powers,J.C.(1985)Biochemistry,24,2040-2047.
Riekkinen,P.J., Ekfors,T.O., Hollmen,T.,and Hopsu Havu, V.K.(1967)Enzymology,32,110-127.
Lippoldt,A., Paul,M., Fuxe,K.,and Ganten,D.(1995) Clin.Exp.Hypertens.,17,251-266.
Loscalso,J.,and Braunwald,E.(1988)New Engl.J.Med., 319,925-931.
Vercaigne Marko, D., Carrere,J., Ducourouble,M.P., Davril,M., Laine,A., Amouric,M., Figarella,C.,and Hayem,A.(1987)Biol.Chem.Hoppe Seyler,368,37-45.
Woodbury,P.G.,and Neurath,H.(1981)in Metabolic Interconversion of Enzymes (Holzer,H.,ed.)Academic Press, N.Y.,pp.145-158.
Urata,H., Boehm,K.D., Philip,A., Kinoshita,A., Gabrovsek,J., Bumpus,F.M.,and Husain,A.(1993)J.Clin.Invest.,91,1269-1281.
Wintroub,B.U., Klikstein,L.B., Dzau,V.J.,and Watt,W. K.(1984)Biochemistry,23,345-348.
Senior,R.M.,and Campbell,E.J.(1984)J.Immunol., 132,2547-2551.
Barrett,A.J.(1981)Meth.Enzymol., 80,561-565.
Belova,L.A.(1997)Biochemistry (Moscow),62,659-668 (Russ.).
Peterson,M.W.(1989)J.Lab.Clin.Med., 113,297-308.
Owen,C.A.,and Campbell,E.J.(1998)J.Immunol., 160, 1436-1443.
Dzau,V.J., Gonzalez,D., Kaempfer,C., Dubin,D.,and Wintroub,B.U.(1987)Circ.Res., 60,595-601.
Wolny,A., Clozel,J.P., Rein,J., Mory,P., Turino,M., Kiowski,W.,and Fischli,W.(1997)Circ.Res.,80,219-227.
Marone,G., Casolaro,V., Patella,V., Florio,G.,and Triggiani,M.(1997)Int.Arch.Allergy Immunol., 114,207-217.
Takai,S., Shiota,N., Sakaguchi,M., Muraguchi,H., Matsumura,E.,and Miyazaki,M.(1997)Clin.Chim.Acta, 265,13-20.
Hori,S., Ohtani,S., Hori,C.,and Nokihara,K.(1998)J.Biochem.(Tokyo),123,650-658.
Liao,Y.,and Husain,A.(1995)Can.J.Cardiol.,11 (Suppl. F),13F-19F.
Sanker,S., Chandrasekharan,U.M., Wilk,D., Glynias, M.J., Karnik,S.S.,and Husain,A.(1997)J.Biol.Chem., 272,2963-2968.
Balcells,E., Meng,Q.C., Johnson,W.H., Oparil,S.,and Dell 'Italia, L.(1997)Am.J.Physiol.,273,H1769-H1774.
Urata,H., Strobel,F.,and Ganten,D.(1994)J.Hypertens., 12 (Suppl.),S17-S22.
Daemen,M.J.,and Urata,H.(1997)Heart Vessels,Suppl. 12,113-115.
Okunishi,H., Miyazaki,M., Okamura,T.,and Toda,N. (1987)Biochem.Biophys.Res.Commun.,149,1186-1192.
Okunishi,H., Miyazaki,M.,and Toda,N.(1984)J.Hypertens.,2,277-284.
Urata,H., Kinoshita,A., Misono,K.S., Bumpus,F.M., and Husain,A.(1990)J.Biol.Chem., 265,22348-22357.
Powers,J.C., Tanaka,T., Harper,J.W., Minematsu,Y., Barker,L., Lincoln,D.,and Crumley,K.V.(1985) Biochemistry,24,2048-2058.
Ohmichi,N., Iwai,N., Shimoike,H., Izumi,M., Watarida,S., Mori,A., Nakamura,Y.,and Kinoshita,M. (1997)Heart Vessels,Suppl.12,116-118.
Urata,H.,and Ganten,D.(1993)Eur.Heart J., 14 (Suppl. 1),177-182.
Urata,H., Healy,B., Stewart,R.W., Bumpus,F.,and Husain,A.(1990)Circ.Res., 66,883-890.
Dzau,V.J.(1988)Circulation,77 (Suppl.I),I-1-I-3.
Van Gilst, W.H., Scholtens,E., de Graeff, P.A., de Laagen, C.D.J.,and Wesseling,H.(1988)Circulation,77 (Suppl.I),I-24-I-29.
Skvortsov,A.A., Mareev,V.Yu.,and Belenkov,Yu.N. (1998)Kardiologiya,38,36-50.
Zisman,L.S., Abraham,W.T., Meixell,G.E., Vamvakias, B.N., Quaife,R.A., Lowes,B.D., Roden,R.L., Peacock, S.J., Groves,B.M., Raynolds,M.V., Bristow,M.R.,and Perryman,M.B.(1995)J.Clin.Invest.,95,1490-1498.
Gondo,M., Maruta,H.,and Arakawa,K.(1989)Jpn.Heart J., 30,219-229.
Miura,S., Ideishi,M., Sakai,T., Motoyama,M., Kinoshita,A., Sasaguri,M., Tanaka,H., Shindo,M.,and Arakawa,K.(1994)J.Hypertens., 12,1177-1181.
Urabe,Y., Ideishi,M., Sasaguri,M., Ikeda,M.,and Arakawa,K.(1993)Am.J.Cardiol., 72,218-222.
Roks,A., Buikema,H., Pinto,Y.M.,and van Gilst, W.H. (1997)Heart Vessels,Suppl.12,119-124.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Belova, L.A. Angiotensin II-Generating Enzymes. Biochemistry (Moscow) 65, 1337–1345 (2000). https://doi.org/10.1023/A:1002848402911
Issue Date:
DOI: https://doi.org/10.1023/A:1002848402911