Title: Kinin and angiotensin metabolism by purified renal post-proline cleaving enzyme
Abstract: Post-proline cleaving enzyme (PPCE; EC 3.4.21.26) is a proline specific endopeptidase capable of hydrolyzing biologically active peptides. The present studies examined the hydrolysis of kinin- and angiotensin-related peptides by cytosolic PPCE purified from porcine kidney. PPCE hydrolysis of the synthetic substrate Z-Gly-Pro-MCA (30.7 ± 0.3 μmol · min−1 · mg−1) was competitively inhibited by saralasin, bradykinin, des(Arg9)bradykinin, [Leu8], des(Arg9)bradykinin and angiotensin II (IC50 = 0.5 to 7.0 μM). Qualitative TLC studies demonstrated that each peptide was degraded by hydrolysis on the carboxyl side of proline residues (positions 7 or 8). Quantitative HPLC studies established that peptide degradation was optimal at pH 8.2 to 8.7 and was inhibited by the specific PPCE inhibitor Z-Pro-prolinal (IC50 = 0.8 ± 0.1 nM). Conversely, degradation was unaffected by inhibitors of aminopeptidases (amastatin), neutral endopeptidase (phosphoramidon), carboxypeptidase N (MERGETPA) or angiotensin I converting enzyme (captopril). Apparent Km values, obtained from Lineweaver-Burk analysis, were comparable for all kinin and angiotensin peptides (Km = 5.5 to 12.8 μM), whereas Vmax values ranged from 1.7μmol · min−1 · mg−1 for angiotensin II to 0.44 μmol · min−1 · mg−1 for saralasin. These data are consistent with a role for PPCE in the degradation of kinins and angiotensin in vivo.
Publication Year: 1987
Publication Date: 1987-10-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 33
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