Recent advances in knowledge of the structure and function of the angiotensin I converting enzyme

To review the structure and function of the angiotensin I converting enzyme (ACE), focusing on recent results from studies using a wide range of molecular biological techniques.

ACE is an ectoenzyme expressed as two isoenzymes in mammals, a larger somatic form found in endothelial, epithelial and neuronal tissues and a smaller form in germinal tissues. Both forms have similar enzymatic activities but differ in size and immunological properties. The somatic form of ACE is composed of two highly homologous domains (amino and carboxyl domains) while the germinal form contains only one domain. Somatic ACE has two functional catalytic sites, both dependent on a zinc cofactor. Each ACE domain has also been shown to interact differently with competitive inhibitors.

The mechanism for anchoring ACE to the cell membrane has also been reported, and the solubilization step outlined. The relationship between the membrane-bound and soluble forms has been investigated, and the physiological relevance of this mechanism discussed.

The structure of the ACE gene has been determined and the distribution in cells and different tissues has been reported in various studies.

All results have indicated that there are important functional and structural differences between the two domains, but at present ACE cannot be considered a true bifunctional enzyme, even though an exclusive substrate has been identified for the amino domain.