Angiotensin-converting enzyme somatic C-domain (ACE C-domain)

The Angiotensin-converting enzyme (ACE) somatic C-domain is one of two homologous catalytic domains in the somatic isoform of ACE, a zinc-dependent metallopeptidase that plays a critical role in the renin-angiotensin-aldosterone system (RAAS) [1][5]. While somatic ACE contains both an N-domain and a C-domain, the C-domain is the primary site responsible for converting angiotensin I into the potent vasoconstrictor angiotensin II in vivo [1][3]. It also contributes to the degradation of the vasodilator bradykinin, although the N-domain can compensate for this function [2][7]. Because of its central role in blood pressure regulation, the C-domain is the primary target for ACE inhibitors used to treat hypertension, heart failure, and diabetic nephropathy [4][8]. Most clinically available ACE inhibitors, such as lisinopril and enalapril, are non-selective and bind to both domains, which can lead to side effects like dry cough and angioedema due to excessive bradykinin accumulation [3][6]. Research into selective C-domain inhibitors, such as RXPA380 and keto-ACE, aims to maintain antihypertensive efficacy while potentially reducing these adverse effects by preserving N-domain activity [2][11].

Other names

cACEC-terminal domain of ACETestis ACEGerminal ACEPeptidyl-dipeptidase AKininase II

Inhibition of the zinc-dependent dipeptidyl carboxypeptidase activity, primarily preventing the conversion of Angiotensin I to Angiotensin II.