Inhibitor Analysis of Angiotensin I-Converting and Kinin-Degrading Activities of Bovine Lung and Testicular Angiotensin-Converting Enzyme

S. V. Grinshtein¹, P. V. Binevski¹, O. A. Gomazkov², V. F. Pozdnev², I. I. Nikolskaya¹, and O. A. Kost^1*

¹School of Chemistry, Lomonosov Moscow State University, Moscow, 119899 Russia; fax: (095) 939-5417; E-mail: kost@enzyme.chem.msu.su

²Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, ul. Pogodinskaya 10, Moscow, 119832 Russia; fax: (095) 245-0857; E-mail: inst@ibmh.msk.su

^* To whom correspondence should be addressed.

Received December 18, 1998; Revision received February 2, 1999

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Inhibition of bovine lung and testicular angiotensin-converting enzyme (ACE) by some well-known ACE inhibitors (lisinopril, captopril, enalapril), new substances (N^alpha-carboxyalkyl dipeptides PP-09, PP-35, and PP-36), and phosphoramidon was investigated using Cbz-Phe-His-Leu and FA-Phe-Phe-Arg (C-terminal analogs of angiotensin I and bradykinin, respectively) as the substrates. The somatic (two domains) and testicular (single domain) isoenzymes demonstrated different kinetic parameters for hydrolysis of these substrates. All of the inhibitors were competitive inhibitors of both ACE isoforms, and the K_i values were substrate-independent. The relative potencies of the inhibitors for both enzymes were: lisinopril > captopril > PP-09 > enalapril > PP-36 > PP-35 > phosphoramidon. The inhibition efficiency of PP-09 was comparable with those of the well-known ACE inhibitors. Captopril was more effectively bound to the somatic ACE (K_i = 0.5 nM) than to the testicular isoform (K_i = 6.5 nM).

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KEY WORDS:angiotensin-converting enzyme, somatic form, testicular form, binary activity, metalloproteinase inhibitors, inhibition constants, kinetic parameters

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