Angiotensin-converting enzyme: a well-known stranger. Part I

Abstract

The angiotensin-converting enzyme (ACE) was discovered in 1956 and has been actively studied to date. It has a unique structure of two homologous domains, each containing a catalytic zinc ion. Domains have different substrate specificity. In terms of function, ACE is a zinc metallopeptidase widely present on the surface of endothelial and epithelial cells. The gene encoding ACE is located on the long arm of chromosome 17 (17q23) and is 21 kb long, including 26 exons and 25 introns. The structure of ACE may be the result of an ancient gene duplication that occurred approximately 700 million years ago. The main function of ACE is the conversion of AngI to the vasoconstrictor AngII, which is the main active product. In addition, ACE metabolizes bradykinin, which is a potent vasodilator. ACE is involved in the metabolism of other angiotensins, in particular Ang(1–7), forming, together with ACE 2 and other components of the renin-angiotensin-aldosterone system (RAAS), a complex balanced system for maintaining blood pressure, water and electrolyte balance, and many other components of systemic, tissue and cellular homeostasis that have not yet been fully studied. More data are accumulating confirming the role of ACE for the renal development, early hematopoiesis, normal male fertility, erythropoiesis, myelopoiesis. ACE plays important roles in the immune response, intracellular signaling.