Angiotensin I-converting enzyme

Angiotensin I-converting enzyme (ACE) is a central component of the renin-angiotensin system (RAS), which plays a crucial role in regulating blood pressure, fluid balance, and electrolyte balance in the body. ACE is an enzyme that catalyzes the conversion of angiotensin I, an inactive decapeptide, into angiotensin II, a potent vasoconstrictor and a stimulator of aldosterone secretion from the adrenal glands. This process is essential for maintaining vascular tone and sodium homeostasis.

Structure and Function

ACE is a zinc-containing peptidase that is primarily expressed on the luminal surface of endothelial cells in the lungs, but it can also be found in various other tissues, including the kidney, heart, and brain. The enzyme has two main domains, N and C, each containing a catalytic site that is capable of converting angiotensin I to angiotensin II independently.

The primary function of ACE is to facilitate the conversion of angiotensin I to angiotensin II. However, it also plays a role in the degradation of bradykinin, a potent vasodilator, thereby indirectly contributing to the regulation of blood pressure.

Clinical Significance

The activity of ACE and the levels of angiotensin II in the body are of significant interest in the context of hypertension (high blood pressure) and cardiovascular diseases. Inhibitors of ACE, known as ACE inhibitors, are commonly used in the treatment of these conditions. By blocking the conversion of angiotensin I to angiotensin II, ACE inhibitors help to lower blood pressure, reduce cardiac workload, and provide protection against heart failure and kidney failure.

Genetic variations in the ACE gene have been associated with susceptibility to various cardiovascular and renal diseases. For example, an insertion/deletion (I/D) polymorphism in the ACE gene has been linked to differences in the serum concentration of the enzyme and, consequently, to variations in individual responses to ACE inhibitors.

Research and Future Directions

Research into ACE and the broader renin-angiotensin system continues to uncover new roles for these components in health and disease. Beyond their established roles in cardiovascular and renal physiology, studies have suggested that ACE and angiotensin II may also be involved in processes such as inflammation, fibrosis, and the response to injury.

Emerging therapies targeting ACE, angiotensin II, and other elements of the renin-angiotensin system are being developed to treat a wider range of conditions, including diabetes mellitus, fibrotic diseases, and certain types of cancer. These advances highlight the ongoing importance of understanding ACE's structure, function, and regulation.