What is the Difference Between ACE1 and ACE2

ACE1 and ACE2 are two important enzymes involved in the renin-angiotensin-aldosterone system (RAAS). ACE2 enzyme plays an important function in this system. It acts as a counterbalance to ACE 1. ACE1 cleaves the angiotensin I hormone into the vasoconstricting angiotensin II, which leads to an increase in the body’s blood pressure. ACE2 has an opposing effect to ACE1. It degrades angiotensin II into angiotensin (1-7). This lowers the blood pressure.

The key difference between ACE1 and ACE2 is their function. ACE1 cleaves angiotensin I hormone into the vasoconstricting angiotensin II, which causes an increase in the body’s blood pressure, while ACE2 degrades angiotensin II into angiotensin (1-7), thereby lowering blood pressure.

CONTENTS

1. Overview and Key Difference
2. What is ACE1  
3. What is ACE2
4. Similarities – ACE1 and ACE2
5. ACE1 vs ACE2 in Tabular Form
6. Summary – ACE1 vs ACE2
7. FAQ – ACE1 and ACE2

What is ACE1?

ACE1 is the central component of the renin–angiotensin aldosterone system (RAAS). This enzyme controls blood pressure by regulating the volume of fluids in the body. ACE1 usually converts the angiotensin I hormone into angiotensin II hormone. Angiotensin II is an active vasoconstrictor. Therefore, ACE1 indirectly increases blood pressure by causing constriction of blood vessels. Moreover, ACE 1 is highly expressed in highly vascular organs such as the retina and lung. However, it can also be found in blood vessels, kidneys, intestines, adrenal glands, liver, and uterus.

Figure 01: Renin-Angiotensin-Aldosterone System

High blood pressure is widely associated with cardiovascular diseases. Therefore, ACE1 inhibitors are widely used in the pharmaceutical industry as a drug for the treatment of cardiovascular diseases. Furthermore, ACE1 is also part of the kinin–kallikrein system. This system degrades bradykinin, a potent vasodilator, and other vasoactive peptides.

What is ACE2?

ACE2 is an enzyme in the protective phase of the RAAS system. ACE2 can be found attached to the membrane of cells in the intestines, testis, gallbladder, kidney,  and heart. This is the membrane-bound form of ACE2 known as mACE2. Moreover, it can also be found in the soluble form (sACE2).

Figure 02: ACE2

ACE2 enzyme activity opposes the classical process of the RAAS system. ACE2 lowers blood pressure by catalyzing the hydrolysis of angiotensin II into angiotensin1-7. Angiotensin1-7 is a vasodilator. It binds to MasR receptors, creating localized vasodilation and hence decreasing blood pressure. Furthermore, ACE2 also regulates the membrane trafficking of the neutral amino acid transporter SLC6A19 and it is involved in the regulation of the blood glucose level.

Similarities Between ACE1 and ACE2

1. ACE1 and ACE2 are two enzymes in the RAAS system.
2. ACE2 is a homolog of the ACE1.
3. Both are protein molecules.
4. Both play important roles.
5. Changes in these enzymes result in abnormal blood pressure in the body.

Difference Between ACE1 and ACE2

Definition

1. ACE1 is an enzyme in the RAAS system that converts angiotensin I to angiotensin II.
2. ACE2 is an enzyme in the RAAS system that converts angiotensin I to angiotensin1-7.

Expressed in

1. ACE 1 is highly expressed in highly vascular organs such as the retina and lungs, and it also can be found in blood vessels, kidneys, intestines, adrenal glands, liver, and uterus.
2. ACE2 can be found attached to the membrane of cells (mACE2) in the intestines, kidney, testis, gallbladder, and heart or can be found in the soluble form (sACE2).

Effect on Blood Pressure

1. ACE 1 increases blood pressure.
2. ACE2 decreases blood pressure.

Function

1. ACE1 indirectly increases blood pressure by causing constriction of the blood vessels; it is also part of the kinin–kallikrein system and degrades bradykinin, a potent vasodilator, and other vasoactive peptides.
2. ACE2 acts in the protective phase of the RASS system by decreasing the blood pressure increased by angiotensin II by converting it to angiotensin1-7, and it also regulates the membrane trafficking of the neutral amino acid transporter SLC6A19and it is involved in the regulation of the blood glucose level.

This summarizes the difference between ACE1 and ACE2.

Summary – ACE1 vs ACE2

The renin-angiotensin-aldosterone system (RAAS) is an important part of the body for blood pressure regulation. ACE1 and ACE2 are two enzymes in the RAAS system.ACE1 converts angiotensin I to angiotensin II vasoconstrictor while ACE2 converts angiotensin I to angiotensin1-7 vasodilator. Furthermore, ACE 1 increases the blood pressure in the body, whereas ACE2 decreases the blood pressure in the body. This is the summary of the difference between ACE1 and ACE2.

FAQ: ACE1 and ACE2

1. What are the main steps of the RAAS system?

• The main steps in the RAAS pathway include releasing the renin, conversion of angiotensinogen to angiotensin I, and formation of angiotensin II. Angiotensin II subsequently acts on various bodily systems to increase blood pressure. Moreover, when blood pressure is in the normal range, a substance called atrial-natriuretic peptide shuts down the RAAS system.

2. Why is the RAAS system activated?

• RAAS system is normally activated when there is a drop in blood pressure or reduced blood volume in order to increase water and electrolyte reabsorption in the kidney. This process compensates for the drop in blood volume, ultimately increasing blood pressure.

3. Which drugs are ACE inhibitors?

• Angiotensin-converting enzyme 1 (ACE1) converts angiotensin I to angiotensin II. ACE inhibitors prevent an enzyme in the body from making angiotensin II, thus decreasing blood pressure. ACE inhibitors include Benazepril, Captopril, Enalapril, Fosinopril, Lisinopril, Moexipril, Perindopril, Quinapril, and Ramipril.

4. What is the function of ACE2 in the body?

• Angiotensin-converting enzyme 2 (ACE2) is a homologue of ACE1. ACE2 is a zinc metalloenzyme and carboxypeptidase located as an ectoenzyme on the surface of endothelial and other cells. It acts as its physiological counterbalance, providing homeostatic regulation of circulating angiotensin II levels by converting it to angiotensin1-7.

5. What is the main function of aldosterone?

• Angiotensin II triggers the adrenal glands to release aldosterone. Aldosterone regulates the body’s salt and water balance by increasing the retention of sodium and water and the excretion of potassium by the kidneys.

Reference:

1.  “Angiotensin-Converting Enzyme 2.” ScienceDirect Topics.
2.  Riordan, James F. “Angiotensin-i-Converting Enzyme and Its Relatives.” Genome Biology, U.S. National Library of Medicine.

Image Courtesy:

1. “Renin-angiotensin-aldosterone system” By Soupvector – Own work (CC BY-SA 4.0) via Commons Wikimedia
2. “Active site of human ACE2” By ChemPro – (CC0) via Commons Wikimedia

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