angiotensin maturation

Definition

Target type: biologicalprocess

The process leading to the attainment of the full functional capacity of angiotensin by conversion of angiotensinogen into mature angiotensin in the blood. [ISBN:0721643949]

Angiotensin maturation is a complex process that involves the conversion of angiotensinogen, a large precursor protein produced in the liver, into active angiotensin peptides. The process can be summarized in two key steps:

1. **Renin-mediated cleavage:** Angiotensinogen is cleaved by the enzyme renin, which is released from the juxtaglomerular cells of the kidneys in response to various stimuli, including low blood pressure, low sodium levels, and sympathetic nervous system activation. Renin specifically cleaves angiotensinogen between amino acids 10 and 11, generating angiotensin I (Ang I).

2. **Angiotensin-converting enzyme (ACE) activity:** Ang I is then converted into the biologically active peptide angiotensin II (Ang II) by the enzyme angiotensin-converting enzyme (ACE). ACE is primarily found in the lungs, but it is also present in other tissues, including the kidneys, brain, and heart. ACE cleaves two amino acids from the C-terminal end of Ang I, resulting in Ang II.

**Detailed Description:**

* **Angiotensinogen:** This large precursor protein is synthesized in the liver and circulates in the bloodstream. It consists of 452 amino acids and contains the angiotensin sequence within its structure.
* **Renin:** This is an aspartic protease released from the juxtaglomerular cells of the kidneys. It is responsible for the initial cleavage of angiotensinogen, generating Ang I. Renin release is regulated by various factors, including low blood pressure, low sodium levels, and sympathetic nervous system activation.
* **Angiotensin I (Ang I):** This is an inactive peptide that contains 10 amino acids. It is formed by the action of renin on angiotensinogen.
* **Angiotensin-converting enzyme (ACE):** This is a zinc metallopeptidase that converts Ang I into Ang II. It is found in the lungs, kidneys, brain, heart, and other tissues. ACE has a wide range of substrates, including bradykinin, a vasodilator peptide.
* **Angiotensin II (Ang II):** This is the biologically active peptide that acts as a potent vasoconstrictor, stimulating aldosterone release from the adrenal glands, and influencing renal sodium reabsorption. Ang II plays a crucial role in regulating blood pressure and fluid balance.

**Regulation of Angiotensin Maturation:**

The maturation of angiotensin is tightly regulated by various factors, including:

* **Renin release:** Renin release is primarily controlled by the renin-angiotensin-aldosterone system (RAAS), which is a complex hormonal cascade that regulates blood pressure and fluid balance.
* **ACE activity:** ACE activity can be influenced by various factors, including drugs like ACE inhibitors, which are commonly used to treat hypertension.
* **Other factors:** Other factors that can influence angiotensin maturation include stress, diet, and genetic predisposition.

**Biological Significance:**

Angiotensin maturation is a critical process for maintaining blood pressure and fluid balance. Ang II, the final product of this process, plays a vital role in regulating various physiological processes, including:

* **Vasoconstriction:** Ang II causes constriction of blood vessels, leading to increased blood pressure.
* **Aldosterone release:** Ang II stimulates the release of aldosterone from the adrenal glands, which promotes sodium and water retention in the kidneys.
* **Renal sodium reabsorption:** Ang II directly stimulates sodium reabsorption in the kidneys, contributing to fluid retention.
* **Thirst stimulation:** Ang II can stimulate thirst, leading to increased fluid intake.
* **Other effects:** Ang II also exerts effects on the heart, brain, and other organs.

**Clinical Relevance:**

Dysregulation of the angiotensin maturation process can lead to various health problems, including:

* **Hypertension:** Increased angiotensin II levels can contribute to high blood pressure.
* **Heart failure:** Ang II can exacerbate heart failure by constricting blood vessels and increasing afterload on the heart.
* **Kidney disease:** Ang II can contribute to kidney disease by promoting vasoconstriction and sodium retention.
* **Other conditions:** Angiotensin II has been implicated in various other conditions, including stroke, diabetes, and preeclampsia.

**Therapeutic Interventions:**

Therapeutic interventions targeting the angiotensin maturation process include:

* **ACE inhibitors:** These drugs block the activity of ACE, reducing the conversion of Ang I to Ang II and lowering blood pressure.
* **Angiotensin II receptor blockers (ARBs):** These drugs block the binding of Ang II to its receptors, preventing its vasoconstrictive and other effects.

Angiotensin maturation is a complex and tightly regulated process that plays a vital role in maintaining blood pressure and fluid balance. Understanding this process is crucial for understanding the pathogenesis of various diseases and for developing effective therapeutic interventions.'
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Proteins (12)

Compounds (238)