The angiotensin I-converting enzyme (kininase II): Molecular organization and regulation of its expression in humans

O. Costerousse, E. Jaspard, L. Wei, P. Corvol, F. Alhenc-Gelas

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Protein sequencing and molecular cloning of human endothelial angiotensin I-converting enzyme (ACE; kininase II), have led to a description of the structure of the enzyme and to several questions concerning the intracellular maturation of ACE and the mechanisms of enzyme action. With the help of recombinant ACE expression in mammalian cells and site-directed mutagenesis, a model for the maturation of ACE in endothelial cells has been proposed. This model comprises transmembrane anchoring of the membrane-bound ACE near its carboxyterminal extremity, and post-translational cleavage of the anchor in the secreted form. The endothelial ACE displays a high degree of internal homology between two large peptidic domains that each bears a consensus sequence for zinc binding and therefore a putative active site. The testicular ACE, however, encoded from the same gene by a shorter mRNA, contains only the carboxyterminal half of endothelial ACE and therefore a single active site. Expression of ACE mutants with only one intact homologous domain, however, indicates that in endothelial ACE both domains are enzymatically active. Further characterization of these two active sites of endothelial ACE is in progress. In humans, population studies have indicated that the large interindividual variability in plasma ACE levels is partly genetically determined and under the influence of a major gene effect. This was later confirmed and extended by the observation of an insertion-deletion polymorphism of the ACE gene that is associated with the level of ACE in plasma. The clinical implications of these observations are discussed.

Original languageEnglish (US)
Pages (from-to)S10-S15
JournalJournal of cardiovascular pharmacology
Volume20
Issue number9
DOIs
StatePublished - Dec 1992
Externally publishedYes

Keywords

  • Angiotensin-converting enzyme
  • Endothelial cells

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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