Angiotensin-converting enzyme 2 (ACE2) is a type I transmembrane metallocarboxypeptidase within the renin-angiotensin system (RAS), which plays a key role in blood pressure regulation, fluid and electrolyte balance, thirst, cardiac/renal function and growth. ACE2 is expressed on the cell surface of type 2 alveolar epithelial cells in the lungs as well as on cells in many other tissues. ACE2 shares approximately 60% homology with ACE, the other key enzyme of the RAS system.
ACE2 converts angiotensin II (Ang II) into Ang(1–7), which acts on the Mas receptor and plays a role in cardiovascular disease to lower blood pressure through vasodilation and by promoting kidney sodium and water excretion, but also to lower inflammation. The effects of ACE2 directly oppose those induced by ACE–Ang II signalling, whereby ACE converts Ang I into Ang II, which increases blood pressure by inducing vasoconstriction, increasing kidney reabsorption of sodium and water and promoting inflammation.
ACE2 has been identified as a key receptor on target cells for SARS-CoV infections in 2002. ACE2 functions as the entry receptor of the new SARS-CoV-2 coronavirus that emerged in China in 2019 and is the cause of the new disease COVID-19. Strong binding of the spike protein of SARS-CoV-2 to ACE2, along with proteolytic cleavage of ACE2 by transmembrane serine protease 2 (TMPRSS2), facilitates entry of the virus into cells, viral replication and cell-to-cell transmission. The spike protein priming by the co-receptor serine protease TMPRSS2 is crucial for SARS-CoV-2 infection of target cells and the spread of the coronavirus throughout the host (see Figure 3).
LITERATURE REFERENCES:
- Angiotensin Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: M. Gheblawi, et al.; Circ. Res. (Epub ahead of print) (2020)
- SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor: M. Hoffmann, et al.; Cell (Epub ahead of print) (2020)
Originally posted on adipogen.com/covid-19
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