Hydrolysis of a synthetic angiotensin-converting enzyme substrate in dog lungs.
The present study was carried out to begin to evaluate the saturable kinetics of the hydrolysis of a synthetic substrate, benzoyl-phenylalanyl-alanyl-proline (BPAP), for angiotensin-converting enzyme (ACE), by the pulmonary endothelium of the dog using a multiple indicator dilution method. In the experiments, isolated dog lung lobes were perfused with a salt solution containing 5% bovine serum albumin. Boluses containing [3H]BPAP, and various amounts of unlabeled BPAP were injected into the lobar artery, and timed samples of venous effluent were collected. The samples were analyzed to determine the fractional hydrolysis of the injected BPAP. The BPAP hydrolysis on passage through the lungs exhibited the saturable behavior and the relative insensitivity to changing flow rate previously described. Since we have described previously that BPAP behaves as if it exists in two forms, one of which is virtually unhydrolyzable on a single pass through the lungs, a model was formulated to include the influence of the unhydrolyzable form, as well as the saturable hydrolysis of the hydrolyzable form, on the fractional hydrolysis of the injected BPAP. This model provides a new method for estimating the kinetic parameters of BPAP hydrolysis by pulmonary endothelial ACE, and it explains the observation that the fractional BPAP hydrolysis does not vary with flow rate and transit time to the extent predicted by previous models.
Linehan
J H
JH
Department of Biomedical Engineering, Marquette University, Milwaukee 53233.
Bronikowski
T A
TA
Rickaby
D A
DA
Dawson
C A
CA
D000818:Animals; D004285:Dogs; D006868:Hydrolysis; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008433:Mathematics; D008962:Models, Theoretical; D009842:Oligopeptides / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011865:Radioisotope Dilution Technique; D014316:Tritium
D009842:Oligopeptides; D014316:Tritium; C029689:benzoylphenylalanyl-alanyl-proline; D007703:Peptidyl-Dipeptidase A