86 by: Hannah Goddard
Student – Hannah Goddard
Enzyme: Angiotensin Converting Enzyme (ACE)
EC number: 3.4.15.1
The Somatic ACE enzyme is mainly found in the lung tissues, but can also be found in blood vessels, intestines, liver, kidney, and other organs. It is a membrane bound enzyme, bound to the surface of epithelial and endothelial cells, lining internal organs.
ACE is involved in the conversion of angiotensin I to angiotensin II, which is a major function in controlling blood pressure. The reaction conducted is the removal of a terminal dipeptide (His-Leu) from Ang I, forming Ang II. The increase of Ang II produced causes the walls of blood vessels and arteries to constrict, therefore increasing blood pressure. Since ACE is classified as a metalloenzyme, it’s catalytic activity is dependant on zinc and chloride metals in it’s active site. As the substrate (Ang I) enters the active site, it is immediately stabilized by the zinc ion. A water molecule in the active site gets deprotonated, then is responsible for adding alcohol to the target amino acid. Then, the unstable dipeptide cleaves it’s bond with the rest of the peptide, resulting in the formation of Ang II.
Extra enzyme information:
• Another form of ACE is Testis ACE, found in the male germ cells
• Another main reaction completed by somatic ACE is the degradation of bradykinin
References
• Tzakos, A. G., Galanis, A. S., Spyroulias, G. A., Cordopatis, P., Manessi-Zoupa, E., & Gerothanassis, I. P. (2003). Structure-function discrimination of the N- and C- catalytic domains of human angiotensin-converting enzyme: implications for Cl- activation and peptide hydrolysis mechanisms. Protein Engineering Design and Selection, 16(12), 993–1003. https://doi.org/10.1093/protein/gzg122
• Thornton Group. (n.d.). M-CSA Mechanism and Catalytic site Atlas. https://www.ebi.ac.uk/thornton-srv/m-csa/entry/170/
• Wong M. K. S. (2016). Angiotensin Converting Enzymes. Handbook of Hormones, 263–e29D-4. https://doi.org/10.1016/B978-0-12-801028-0.00254-3
• Leong, D. P., McMurray, J. J., Joseph, P. G., & Yusuf, S. (2019). From ACE Inhibitors/ARBs to ARNIs in coronary artery disease and heart Failure (Part 2/5). Journal of the American College of Cardiology, 74(5), 683–698. https://doi.org/10.1016/j.jacc.2019.04.068
