L'enzyme de conversion de l'angiotensine (kininase II). Aspects moléculaires et physiologiques.

Translated title of the contribution: Angiotensin converting enzyme (kininase II). Molecular and physiological aspects

O. Costerousse, E. Jaspard, J. Allegrini, Lei Wei, F. Alhenc-Gelas

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The angiotensin I-converting enzyme (kininase II, ECA) is a membrane bound enzyme anchored to the cell membrane through a single transmembrane domain located near its carboxyterminal extremity. Secretion of ACE by the cell occurs most likely as a result of a posttranslational cleavage of the membrane anchor and intracellular region. The ACE molecule is organized into two large highly homologous domains, each bearing consensus sequences for zinc binding in metallopeptidases. Site directed mutagenesis allowed to establish that both domains bear in fact a functional active site, able to convert angiotensin I into angiotensin II and to hydrolyze bradykinin or substance P. The two active sites of ACE, however, do not display the same sensitivity to anion activation (the C terminal active site being more chloride activatable) and also differs in kinetic parameters for peptide hydrolysis. The C terminal active site can hydrolyze faster angiotensin I and substance P and the N terminal active site is able to perform a peculiar endoproteolytic cleavage of an in vitro substrate of ACE, the luteinizing hormone releasing hormone. Both active sites bind with a high affinity, competitive inhibitors but the Kd of the reaction can vary up to 10 between the two active sites. All together, these observations suggest that ACE contains two active sites, whose structure is not exactly identical. They may have a different substrate specificity, however this remains speculative at the present time. Concerning the regulation of ACE gene expression in man, population studies indicated that the large interindividual variability in plasma ACE levels is genetically determined. An insertion/deletion polymorphism located in an intron of ACE gene is associated with differences in the level of ACE in plasma and cells. The physiological and clinical implications of these observations is discussed.

Original languageFrench
Pages (from-to)586-598
Number of pages13
JournalComptes Rendus des Seances de la Societe de Biologie et de Ses Filiales
Volume186
Issue number6
StatePublished - 1992
Externally publishedYes

Fingerprint

Angiotensin I
Peptidyl-Dipeptidase A
Substance P
Catalytic Domain
Bearings (structural)
Membranes
Plasmas
Mutagenesis
Metalloproteases
Bradykinin
Substrates
Cell membranes
Anchors
Polymorphism
Kinetic parameters
Gene expression
Gonadotropin-Releasing Hormone
Angiotensin II
Introns
Anions

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

L'enzyme de conversion de l'angiotensine (kininase II). Aspects moléculaires et physiologiques. / Costerousse, O.; Jaspard, E.; Allegrini, J.; Wei, Lei; Alhenc-Gelas, F.

In: Comptes Rendus des Seances de la Societe de Biologie et de Ses Filiales, Vol. 186, No. 6, 1992, p. 586-598.

Research output: Contribution to journalArticle

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