RECENT ADVANCES IN KNOWLEDGE OF THE STRUCTURE AND FUNCTION OF THE ANGIOTENSIN-I CONVERTING-ENZYME

Aim: To review the structure and function of the angiotensin I convert ing enzyme (ACE), focusing on recent results from studies using a wide range of molecular biological techniques. ACE structure and function: ACE is an ectoenzyme expressed as two isoenzymes in mammals, a larger somatic form found in endothelial, epithelial and neuronal tissues an d a smaller form in germinal tissues. Both forms have similar enzymati c activities but differ in size and immunological properties. The soma tic form of ACE is composed of two highly homologous domains (amino an d carboxyl domains) while the germinal form contains only one domain. Somatic ACE has two functional catalytic sites, both dependent on a zi nc cofactor. Each ACE domain has also been shown to interact different ly with competitive inhibitors. Mechanism of ACE anchorage and solubil ization: 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, a nd the physiological relevance of this mechanism discussed. Genetic st ructure: The structure of the ACE gene has been determined and the dis tribution in cells and different tissues has been reported in various studies. Conclusion: All results have indicated that there are importa nt functional and structural differences between the two domains, but at present ACE cannot be considered a true bifunctional enzyme, even t hough an exclusive substrate has been identified for the amino domain.