Question 1

What is the Meaning of Neprilysin?

Accepted Answer

Neprilysin is a neutral endopeptidase enzyme that degrades various endogenous vasoactive peptides, including natriuretic peptides (ANP, BNP), bradykinin, and angiotensin II. This enzymatic action inactivates these substances, crucial for regulating cardiovascular and renal homeostasis, directly influencing blood pressure and fluid balance.

Question 2

What is the Context of Neprilysin?

Accepted Answer

This enzyme is widely distributed across tissues like kidneys, lungs, heart, and brain. Neprilysin operates within critical physiological systems, notably influencing the renin-angiotensin-aldosterone and natriuretic peptide systems. Its activity modulates circulating peptide levels, directly impacting vascular tone, fluid excretion, and cardiac function.

Question 3

What is the Significance of Neprilysin?

Accepted Answer

Clinically, neprilysin is a key therapeutic target, particularly in chronic heart failure management. Inhibiting neprilysin allows beneficial natriuretic peptides to accumulate, improving cardiac hemodynamics and reducing symptoms. This enzymatic modulation alleviates cardiac stress, enhances sodium and water excretion, and mitigates adverse cardiac remodeling, contributing to patient outcomes.

Question 4

What is the Mechanism of Neprilysin?

Accepted Answer

Neprilysin functions as a cell surface enzyme cleaving peptide bonds, specifically targeting the amino side of hydrophobic amino acid residues within its substrate peptides. This degradation inactivates target peptides, diminishing their biological signaling. For instance, on natriuretic peptides, it reduces their vasodilatory and diuretic effects, while bradykinin degradation limits anti-inflammatory and vasodilatory actions.

Question 5

What is the Application of Neprilysin?

Accepted Answer

Neprilysin modulation applies clinically through sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI) in chronic heart failure with reduced ejection fraction. This medication simultaneously blocks the AT1 receptor and prevents natriuretic peptide breakdown. Dual action enhances beneficial natriuretic effects and counteracts detrimental angiotensin II, improving cardiac function and reducing hospitalizations.

Question 6

What is the Metric of Neprilysin?

Accepted Answer

Neprilysin activity is not directly measured. Its therapeutic effects are assessed via indirect clinical and lab parameters. Monitoring involves heart failure symptom improvements, N-terminal pro-B-type natriuretic peptide (NT-proBNP) level changes, and cardiovascular function. Blood pressure, renal function (creatinine, eGFR), and electrolytes are regularly checked for safety and efficacy.

Question 7

What is the Risk of Neprilysin?

Accepted Answer

Inhibition of neprilysin carries specific clinical risks, notably angioedema risk due to elevated bradykinin levels, especially when combined with ACE inhibitors. Other potential adverse effects include symptomatic hypotension, hyperkalemia, and renal impairment. Therefore, careful patient selection, avoiding concurrent ACE inhibitor use, and close monitoring are essential to mitigate risks.

Neprilysin

Meaning

Context

Significance

Mechanism

Application

Metric

Risk

What Are the Molecular Mechanisms of Peptide Degradation?