angiotensin-converting enzyme

ACE is a zinc-dependent dipeptidyl carboxypeptidase located mainly on the luminal surface of vascular endothelial cells, especially in the pulmonary capillaries, as well as in the kidney and other tissues. It has two primary functions: (1) converting angiotensin I (inactive decapeptide) to angiotensin II (active octapeptide), a potent vasoconstrictor that also stimulates aldosterone release from the adrenal cortex, promotes sodium and water reabsorption, and triggers ADH release; and (2) degrading bradykinin, a vasodilator peptide, into inactive fragments. Angiotensin II acts on AT1 receptors in vascular smooth muscle to cause vasoconstriction and increase blood pressure, and stimulates aldosterone secretion, leading to Na+/water retention and K+ excretion. Clinically, ACE is a major pharmacologic target. ACE inhibitors (e.g., lisinopril, enalapril, captopril) block angiotensin II formation and reduce bradykinin degradation, leading to decreased vasoconstriction, decreased aldosterone secretion, and vasodilation. This class is first-line in hypertension, heart failure (reduces afterload/preload and mortality), diabetic nephropathy (reduces efferent arteriolar resistance, decreasing intraglomerular pressure and proteinuria), and post-MI remodeling. Adverse effects related to ACE inhibition include dry cough and angioedema (due to bradykinin accumulation), hyperkalemia (reduced aldosterone), acute kidney injury in bilateral renal artery stenosis (due to loss of efferent arteriolar constriction), and teratogenicity (fetal renal malformations, contraindicated in pregnancy). ACE levels are also elevated in sarcoidosis and used as a supportive diagnostic marker, reflecting granuloma-derived ACE production by epithelioid cells. Understanding ACE's dual substrate specificity (angiotensin I and bradykinin) is essential for predicting both the therapeutic effects and side-effect profile of ACE inhibitors, a frequently tested concept on USMLE Step 1 and Step 2.