Kinetic properties of the angiotensin converting enzyme inhibitor ramiprilat.
The interaction of angiotensin converting enzyme (ACE) with ramiprilat was studied at pH 7.5 in the presence of 300 mmol/l sodium chloride with furanacryloyl-Phe-Gly-Gly as substrate. Ramiprilat inhibits ACE with a Ki value of 7 pmol/l. It is both a slow- and tight-binding inhibitor; the mode of inhibition is fully competitive. Binding of ramiprilat to ACE proceeds by a two-step mechanism E + I in equilibrium EI in equilibrium EI* in which the inhibitor rapidly binds to enzyme to form an initial enzyme-inhibitor complex, which then undergoes a slow isomerization. The interaction of ramiprilat with ACE is compared to that of two other potent inhibitors, captopril and enalaprilat.
Bünning
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Biochemisches Institut, Universität Freiburg, F.R.G.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D008954:Models, Biological; D011758:Pyrroles / Q000493:pharmacokinetics / Q000494:pharmacology*; D017257:Ramipril / Q000031:analogs & derivatives*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011758:Pyrroles; C052549:ramiprilat; D017257:Ramipril