Angiotensin converting enzyme
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Angiotensin-Converting Enzyme: Functions and Implications
Introduction to Angiotensin-Converting Enzyme (ACE)
Angiotensin-converting enzyme (ACE) is a critical component of the renin-angiotensin system (RAS), primarily responsible for converting angiotensin I into the potent vasoconstrictor angiotensin II, which plays a significant role in regulating blood pressure and fluid-electrolyte balance . ACE is a zinc-dependent peptidase with two homologous catalytic domains, each contributing to its broad substrate specificity and diverse physiological impacts.
ACE and Its Biological Functions
Blood Pressure Regulation and Beyond
ACE's primary function is the conversion of angiotensin I to angiotensin II, a key regulator of blood pressure. However, ACE also inactivates bradykinin, a peptide that promotes vasodilation, thus contributing to its role in blood pressure regulation. Beyond this, ACE influences various physiological processes, including renal development, male reproduction, and immune responses .
Role in Immunity
ACE modulates both innate and adaptive immune responses. It enhances macrophage and neutrophil functions, increasing their effectiveness against tumors and infections. This immune modulation is independent of angiotensin II, highlighting ACE's broader biological roles.
ACE2: A Homologue with Distinct Functions
Discovery and Structure
ACE2, a homologue of ACE, was identified from a human heart failure ventricle cDNA library. It shares 42% identity with ACE in its metalloprotease catalytic domains but has distinct structural and functional properties. Unlike ACE, ACE2 is primarily expressed in the heart, kidney, and testis, and it is not inhibited by common ACE inhibitors like lisinopril or captopril.
Enzymatic Activity and Physiological Roles
ACE2 converts angiotensin I to angiotensin 1-9, which is further processed to angiotensin 1-7, a peptide with vasodilatory and anti-proliferative effects, counteracting the actions of angiotensin II . This conversion pathway positions ACE2 as a crucial modulator within the RAS, offering a counter-regulatory mechanism to the vasoconstrictive and proliferative effects of ACE and angiotensin II.
Therapeutic Potential
ACE2's ability to degrade angiotensin II and produce angiotensin 1-7 has therapeutic implications, particularly in conditions like diabetic nephropathy and cardiovascular diseases. Enhancing ACE2 activity or replenishing its levels has shown promise in reducing hypertension, atherosclerosis, and renal damage .
ACE and ACE2 in Disease and Therapy
Cardiovascular and Renal Diseases
ACE and ACE2 play pivotal roles in cardiovascular and renal health. ACE2 deficiency is associated with elevated angiotensin II levels, leading to hypertension, left ventricular hypertrophy, and increased vascular inflammation. Conversely, ACE2 augmentation can mitigate these effects, suggesting potential therapeutic strategies for managing cardiovascular and renal diseases.
Genetic Variations and Disease Susceptibility
Genetic variations in the ACE gene, particularly the presence or absence of a 287-bp Alu repeat element, have been linked to varying levels of circulating ACE and susceptibility to cardiovascular diseases. However, the associations are complex and sometimes contradictory, indicating the need for further research to understand these genetic influences fully.
Conclusion
Angiotensin-converting enzyme (ACE) and its homologue ACE2 are integral to the renin-angiotensin system, influencing a wide range of physiological processes from blood pressure regulation to immune responses. While ACE primarily converts angiotensin I to angiotensin II, ACE2 provides a counter-regulatory mechanism by converting angiotensin II to angiotensin 1-7. Understanding the distinct and overlapping roles of these enzymes opens new avenues for therapeutic interventions in cardiovascular, renal, and immune-related diseases.
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