Angiotensin-Converting Enzyme

ACE (E.C 3.4.15.1) belongs to the protease family of enzymes and is a membrane-bound zinc metalloenzyme. The zinc ion within ACE directly participates in its protease activity and ACE can be inhibited by metal chelating agents. The ACE gene encodes two isoforms; a long, somatic isoform found in many tissues including vascular endothelial cells and kidney epithelial cells, and a short, germinal isoform expressed only in the testes and sperm.

Within the Renin Angiotensin System, ACE cleaves a C-terminal dipeptide from angiotensin I (Ang I) to release the vasoactive peptide angiotensin II (Ang II). Ang II binds to the angiotensin receptor resulting in vasoconstriction and an increase in blood pressure. ACE is also a component of the kinin-kallikrein system, where it breaks down bradykinin, a vasodilator and proinflammatory peptide.

The brain has its own local Renin Angiotensin System, which modulates cerebrovascular blood pressure. ACE in the brain also cleaves amyloid-β 1-42 (Aβ42) to Aβ40. In Alzheimer's disease (AD), Aβ42 aggregates into toxic amyloid plaques, whereas Aβ40 shows less propensity to aggregate. Higher levels of ACE are therefore suggested to be beneficial in AD.

ACE inhibitors are commonly used to treat hypertension. Similarly, angiotensin receptor blockers (ARBs) are also used to treat hypertension and other cardiovascular disorders. ACE inhibitors reduce the formation of Ang II and inhibit degradation of bradykinin, causing systemic dilation of blood vessels and lowering of blood pressure. Classical ACE inhibitors (with the common suffix, -pril) do not inhibit ACE2.

External sources of pharmacological information for Angiotensin-Converting Enzyme :

• IUPHAR Receptor Code

• BJP Guide

Angiotensin-Converting Enzyme Gene Data