1. The kinetics of the inhibitory action of four different angiotensin-converting enzyme inhibitors was evaluated in vitro with rat lung enzyme and the substrate hippuryl-histidyl-leucine.
2. Enzyme velocity against substrate concentration curves were fitted directly to hyperbolae by a weighted least squares iterative method to obtain apparent values of Km, Vmax. and K/V at each concentration of inhibitor.
3. The inhibitory constants K1 and Kí were obtained by weighted linear regressions of K/V against i and 1/V against i respectively.
4. Teprotide was the least potent inhibitor with a K1 of near 20 nmol/l whereas captopril (SQ 14 225) and SA 446 were both approximately 10 times and MK 421 approximately 20 times more potent.
5. Two inhibitors which lacked thiol groups [teprotide or SQ 20 881 and N-(1-S-1-carboxy-3-phenylpropyl)-l-Ala-l-Pro or MK 421] produced a purely competitive pattern of inhibition with increased apparent Km but no change in apparent Vmax.
6. Two inhibitors containing thiol groups [captopril or SQ 14 225 and 2-(2′-hydroxyphenyl)-3-(3-mercaptopropanoyl)-4-thiazolidine carboxylic acid or SA 446] both produced a mixed competitive and non-competitive pattern of inhibition with increased apparent Km and decreased Vmax.
7. It is possible that thiol-containing inhibitors might produce non-competitive inhibition of converting enzyme by forming strong bonds with zinc near the active site of the enzyme.