Angiotensin conversion

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Angiotensin Conversion: Key Enzymes and Mechanisms

Angiotensin I to Angiotensin II Conversion

Role of Angiotensin-Converting Enzyme (ACE)

Angiotensin-converting enzyme (ACE) is pivotal in the conversion of angiotensin I (Ang I) to angiotensin II (Ang II), a potent vasoconstrictor that plays a crucial role in regulating blood pressure and fluid-electrolyte balance . ACE is a zinc-dependent peptidase found in various tissues, including the vascular endothelial cells of the lungs and peripheral blood vessels, as well as the epithelial cells of kidney tubules. This enzyme not only activates Ang II but also inactivates bradykinin, a peptide that lowers blood pressure.

Genetic Variations and ACE Activity

The ACE gene insertion/deletion (I/D) polymorphism significantly influences ACE levels in the blood. Individuals with one or two D alleles exhibit approximately 25% and 50% higher ACE levels, respectively, compared to those with two I alleles. However, studies show that regional Ang I to Ang II conversion does not necessarily correlate with these genotype-related differences in ACE concentration, suggesting other factors may influence the conversion process.

Angiotensin II to Angiotensin-(1-7) Conversion

Prolyloligopeptidase (POP) and ACE2

The conversion of Ang II to Angiotensin-(1-7) [Ang-(1-7)] involves multiple enzymes, including ACE2, prolylcarboxypeptidase (PRCP), and prolyloligopeptidase (POP). Research indicates that POP is the primary enzyme responsible for this conversion in the circulation and lungs, while ACE2 plays a more significant role in the kidneys. Inhibition of POP markedly reduces Ang-(1-7) formation from Ang II in serum and lung tissues, whereas ACE2 is crucial for this conversion in kidney tissues.

ACE2: A Critical Regulator

ACE2, a homologue of ACE, is a carboxypeptidase that hydrolyzes Ang II to Ang-(1-7), thereby counteracting the vasoconstrictive effects of Ang II . This enzyme is predominantly expressed in the heart, kidneys, and testis, and its activity is not inhibited by traditional ACE inhibitors like lisinopril or captopril. ACE2's role extends beyond blood pressure regulation to include significant impacts on cardiovascular and renal functions.

Functional Implications and Therapeutic Potential

ACE and Cardiovascular Health

ACE's role in converting Ang I to Ang II is well-established, and its inhibition is a common therapeutic strategy for treating hypertension and related cardiovascular diseases. The enzyme's dual catalytic domains contribute to its wide substrate diversity, affecting various physiological processes, including blood pressure control, hematopoiesis, and renal function.

ACE2 and Vascular Remodeling

ACE2 is upregulated in response to vascular diseases and plays a protective role against Ang II-induced vascular remodeling. ACE2 deficiency exacerbates vascular stiffness and smooth muscle cell apoptosis, highlighting its importance in maintaining vascular integrity. The enzyme's ability to metabolize Ang II into Ang-(1-7) provides a counter-regulatory mechanism that mitigates the adverse effects of Ang II.

Conclusion

The conversion of angiotensin peptides is a complex process involving multiple enzymes with distinct roles. ACE is the primary enzyme for converting Ang I to Ang II, while POP and ACE2 are crucial for converting Ang II to Ang-(1-7). Understanding these mechanisms and the genetic variations influencing enzyme activity can inform therapeutic strategies for managing hypertension and cardiovascular diseases.