Faculty Collaboration Database

Impact of angiotensin-converting enzyme substrate conformation on fractional hydrolysis in lung. Am J Physiol 1996 Feb;270(2 Pt 1):L251-9

Date

02/01/1996

Pubmed ID

8779994

DOI

10.1152/ajplung.1996.270.2.L251

Scopus ID

2-s2.0-0029918454 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

We examined the hydrolysis kinetics of benzoyl-phenylalanyl-glycyl-proline (BPGP) in the isolated perfused lung and in vitro for evidence of preferential hydrolysis of the trans isomer by angiotensin-converting enzyme (ACE). Nuclear magnetic resonance spectroscopy showed that BPGP exists as cis and trans isomers in a ratio of 44:56. After a single pass through the perfused rabbit lung over a wide range of infused BPGP concentrations, 42% of the BPGP was not hydrolyzed. In single-pass bolus-injection studies, 41% of the injected BPGP was not hydrolyzed, and very little further hydrolysis occurred in a second passage of the bolus through the lungs. In rat lung recirculation and in vitro studies of BPGP hydrolysis by ACE, approximately 60% of the substrate was hydrolyzed rapidly compared with the remaining approximately 40%, and the peptidyl-prolyl cis-trans isomerase cyclophilin increased the rate of the slower phase of the reaction in both kinds of experiments. We conclude that the rapid hydrolysis phase represents primarily the hydrolysis rate of the trans isomer and the slower phase the cis-trans isomerization rate, suggesting that the trans isomer of BPGP is preferentially hydrolyzed by ACE in the perfused lung and in vitro.

Author List

Merker MP, Armitage IM, Audi SH, Kakalis LT, Linehan JH, Maehl JR, Roerig DL, Dawson CA

Author

Said Audi PhD Professor in the Biomedical Engineering department at Marquette University

MESH terms used to index this publication - Major topics in bold

Animals
Hydrolysis
Lung
Magnetic Resonance Spectroscopy
Models, Biological
Molecular Conformation
Oligopeptides
Peptidyl-Dipeptidase A
Rabbits
Stereoisomerism
Substrate Specificity