Miller J J, Changaris D G, Levy R S
Department of Biochemistry, University of Louisville School of Medicine, Kentucky 40292.
Biochem Biophys Res Commun. 1988 Aug 15;154(3):1122-9. doi: 10.1016/0006-291x(88)90257-4.
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.
我们已经报道了在人肾提取物中存在一种羧肽酶，该酶可分两步将血管紧张素I（AI）转化为血管紧张素II（AII），中间产物为去亮氨酸血管紧张素I（dl-AI）。由于这种羧肽酶的性质与组织蛋白酶A相似，因此研究了组织蛋白酶A代谢AI的能力。从猪肾中纯化组织蛋白酶A，使用苄氧羰基-谷氨酰-酪氨酸（ZGT）和AI作为底物监测酶活性。该过程分离出了预期的组织蛋白酶A的大分子和小分子形式以及另外两种同工酶。所有同工酶对ZGT、AI和dl-AI都具有羧肽酶活性。未观察到AII有可检测到的裂解。以ZGT或AI为底物时，组织蛋白酶A、S（小）活性受到二异丙基氟磷酸酯、汞撒利酸和一种十肽肾素抑制剂的抑制程度相似。得出的结论是，肾血管紧张素羧肽酶活性由组织蛋白酶A催化。通过其将AI转化为AII的能力，组织蛋白酶A可能是肾内肾素-血管紧张素系统的一个组成部分。
