Impact of angiotensin-converting enzyme substrate conformation on fractional hydrolysis in lung

Marilyn P. Merker*, Ian M. Armitage, Said H. Audi, Lazaros T. Kakalis, John H. Linehan, Jeffrey R. Maehl, David L. Roerig, Christopher A. Dawson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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, ~60% of the substrate was hydrolyzed rapidly compared with the remaining ~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.

Original languageEnglish (US)
Pages (from-to)L251-L259
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number2 14-2
StatePublished - Feb 1996


  • cyclophilin
  • cyclosporin A

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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