Angiotensin I-Converting Enzyme (ACE) Gene Structure and Polymorphism: Relation to Enzyme Function and Gene Expression

Angiotensin I-converting enzyme acts primarily as a dipeptidyl carboxypeptidase and is involved in the metabolism of two major vasoactive peptides, angiotensin II and bradykinin. ACE is a membrane-bound enzyme and is orientated such that the catalytic sites are exposed at the extracellular surface of the cell. Due to the association of ACE with the plasma membrane of vascular endothelial cells, the enzyme displays an ubiquitous tissue distribution. The sequence identity between the N- and C-domains is more than 60% over a stretch of 357 amino acids. Each of the two homologous domains contain the consensus sequence found at the active sites of thermolysin, neutral endopeptidase and other zinc peptidases. ACE is the only zinc metallopeptidase known to date to possess two active sites. Some other enzymes contain two active sites and are truly bifunctional since they exhibit distinct functions as, for example, the brush-border hydrolases sucrase-isomaltase and lactase-phlorizin hydrolase.