ACE - Angiotensin I Converting Enzyme |Elisa - Clia - Antibody - Protein

Background

Angiotensin converting enzyme (ACE) is a pivotal enzyme in the Renin-Angiotensin-Aldosterone System (RAAS), a key regulator of blood pressure and fluid balance in the body. ACE plays a crucial role in converting angiotensin I to angiotensin II, a potent vasoconstrictor, thereby increasing blood pressure. ACE inhibitors are commonly prescribed medications that block this conversion, leading to vasodilation and reduced blood pressure. Apart from its role in blood pressure regulation, ACE also has functions in the metabolism of other peptides, including bradykinin. Dysregulation of ACE activity is associated with various cardiovascular diseases, such as hypertension, heart failure, and myocardial infarction. ACE inhibitors are widely used in the management of hypertension, heart failure, and certain kidney diseases. ACE gene polymorphisms have been linked to differences in individual responses to ACE inhibitors and susceptibility to cardiovascular diseases. Understanding the role of ACE has led to the development of novel therapeutic strategies targeting the RAAS for the treatment of cardiovascular disorders.

Protein Structure

ACE is a zinc metalloprotease with two main isoforms:

1. Somatic ACE (sACE): This isoform is expressed in various tissues, including the lungs, kidneys, and vascular endothelial cells. It consists of two homologous domains (N-domain and C-domain), each containing a catalytic site.
2. Testicular ACE (tACE): This isoform is expressed in male germ cells and has a single catalytic domain corresponding to the C-domain of sACE.

Key structural features include:

• Catalytic Domain: Each domain in sACE has a catalytic site containing a zinc ion that is crucial for its enzymatic activity.
• Active Site: The active site of ACE contains the HEXXH motif, which coordinates the zinc ion necessary for catalysis.
• Membrane Anchoring: ACE is a type I membrane-bound enzyme, with a significant portion of its structure extracellular and a short cytoplasmic tail anchoring it to the cell membrane.

Classification and Subtypes

ACE belongs to the M2 family of metallopeptidases and is classified based on its domain structure:

• sACE: Contains two catalytic domains (N- and C-terminal domains).
• tACE: Contains one catalytic domain corresponding to the C-terminal domain of sACE.

Function and Biological Significance

ACE plays several critical roles in physiological processes:

1. Blood Pressure Regulation: By converting angiotensin I to angiotensin II, ACE plays a direct role in increasing blood pressure through vasoconstriction and stimulating aldosterone secretion, which increases sodium and water reabsorption.
2. Electrolyte Balance: ACE-mediated production of angiotensin II influences the kidney's ability to reabsorb sodium and water, thereby regulating blood volume and electrolyte balance.
3. Degradation of Bradykinin: ACE degrades bradykinin, reducing its vasodilatory effect, which contributes to the regulation of vascular tone.
4. Reproductive Functions: tACE is essential in the maturation of spermatozoa and male fertility.

Interactions

ACE interacts with several molecules and proteins:

1. Angiotensin I: The primary substrate for ACE, which is converted into angiotensin II.
2. Bradykinin: A peptide substrate degraded by ACE, reducing its vasodilatory effects.
3. Zinc Ions: Essential cofactors for ACE's enzymatic activity.
4. Other Components of the RAS: ACE works in concert with renin and angiotensinogen to regulate the levels of angiotensin peptides.

Clinical Significance

Dysregulation or inhibition of ACE has significant clinical implications:

1. Hypertension: Overactivity of ACE leads to excessive production of angiotensin II, causing high blood pressure. ACE inhibitors are widely used antihypertensive drugs that block the conversion of angiotensin I to angiotensin II.
2. Heart Failure: ACE inhibitors are also used in the treatment of heart failure to reduce the workload on the heart by lowering blood pressure and decreasing fluid retention.
3. Chronic Kidney Disease: By reducing angiotensin II levels, ACE inhibitors help protect the kidneys from damage due to high blood pressure and proteinuria.
4. ACE Inhibitor-Induced Cough: Inhibition of ACE can lead to an accumulation of bradykinin and substance P, resulting in a persistent cough in some patients.

Summary

Angiotensin I Converting Enzyme (ACE) is a pivotal enzyme in the renin-angiotensin system, playing a crucial role in the regulation of blood pressure and fluid balance. It converts angiotensin I into the potent vasoconstrictor angiotensin II and degrades the vasodilator bradykinin. ACE has two main isoforms: somatic ACE (sACE) with two catalytic domains and testicular ACE (tACE) with one catalytic domain. Dysregulation of ACE activity is associated with hypertension, heart failure, and chronic kidney disease, making it a critical target for therapeutic intervention using ACE inhibitors. Understanding the structure, function, and clinical implications of ACE is essential for managing cardiovascular and renal diseases.