ACE Inhibitors: Mechanism of Action
Angiotensinogen, produced primarily by the liver, is converted to decapeptide, angiotensin I by the enzyme Renin which cleaves the peptide bond between the leucine and valine residues. In addition, it also decreases aldosterone concentration by stimulating its secretion process. ACE cleaves the peptide bond between phenyalanine and histamine to form the octapeptide angiotensin II which is responsible for elevated blood pressure. The active site of ACE was hypothesized to have a positively charged bind to the negatively charged carboxylic group of the substate. Zinc ion, which is contained in the enzyme, is predicted to act in the cleavage of the peptide bond of angiotensin I to form angiotensin II (Figure 1)1.
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Figure 1 A Hypothetical ACE Active Site Figure 2 Succinyl – L – Proline
Interaction with succinyl-L-proline1 (Figure 2) is predicted to inhibit this process. Thus, to increase the binding affinity of……
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