title: Conversion of angiotensin I to angiotensin II by cathepsin A isoenzymes of porcine kidney.
abstract: We have reported the existence of a carboxypeptidase in a human renal extract that converts Angiotensin I (AI) to Angiotensin II (AII) in two steps with des-leu-AI (dl-AI) being formed as an intermediate. Since this carboxypeptidase had properties similar to cathepsin A, the ability of cathepsin A to metabolize AI was studied. Cathepsin A was purified from hog kidney with enzyme activity being monitored using both benzyloxycarbonyl-glutamyl-tyrosine (ZGT) and AI as substrates. The procedure separated the expected large and small molecular weight forms of cathepsin A as well as two additional isoenzymes. All of the isoenzymes had carboxypeptidase activity with ZGT, AI, and dl-AI. No detectable cleavage of AII was observed. Cathepsin A,S (small) activity with ZGT or AI as substrate was inhibited to a similar extent by diisopropylfluorophosphate, mersalyl acid, and a decapeptide renin inhibitor. It is concluded that the renal angiotensin carboxypeptidase activity is catalyzed by cathepsin A. By its ability to convert AI to AII, cathepsin A may be a component of the intrarenal renin-angiotensin system.
authors.affiliation: Department of Biochemistry, University of Louisville School of Medicine, Kentucky 40292.
authors.forename: J J
authors.initials: JJ
authors.lastname: Miller
authors.forename: D G
authors.initials: DG
authors.lastname: Changaris
authors.forename: R S
authors.initials: RS
authors.lastname: Levy
mesh_terms: D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000096:biosynthesis*; D000818:Animals; D002268:Carboxypeptidases / Q000302:isolation & purification / Q000378:metabolism*; D043402:Cathepsin A; D002403:Cathepsins / Q000302:isolation & purification / Q000378:metabolism*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D007527:Isoenzymes / Q000302:isolation & purification / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D013552:Swine
chemical_list: D007527:Isoenzymes; D000804:Angiotensin II; D000803:Angiotensin I; D002268:Carboxypeptidases; D002403:Cathepsins; D043402:Cathepsin A