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ACE Inhibitors

PHRM 304

Schematic drawing shows the structure of ACE. There is a catalytic site on each extracellular lobe, each of which binds a zinc (Zn2+) atom.

Angiotensin Converting Enzyme (ACE) catalyzes hydrolysis of dipeptide fragment Convert of angiotensin I (decapeptide) to angiotensin II (octapeptide) ACE inhibitors are competitive inhibitor

Competitive Inhibition

Non-competitive Inhibition

Angiotensin I Angiotensin II Decapeptide Octapeptide Aspartic acid Arginine ACE Aspartic acid Arginine Valine Tyrosine Valine Tyrosine Isoleucine Histidine Isoleucine Histidine Proline Phenyl alanine Proline Phenyl alanine - Histidine - Leucine

Functions of ACE

Angiotensin I

Bradykinin ACE

Prostaglandin Release

Angiotensin II (Vasoconstrictor) Potent effect

Inactive Bradykinin


Net result is vasoconstriction

Functions of ACE

ACE Side effects

Dry cough in elderly (10-15% patient) Common among women Increase in bradykinin also increase prostaglandin release which causes dry cough

ACE inhibitors
11 approved inhibitors are available Based on chemical composition classified into three groups

I. Sulfhydryl-containing ACE inhibitors


Captopril was the first ACE inhibitor developed

Not a prodrug

II. Dicarboxylate-containing ACE inhibitors

This is the largest group, including: Enalapril

Quinapril Perindopril Lisinopril Esters are act as prodrug

Lisinopril (orally active without being prodrug)

III. Phosphonate-containing ACE inhibitors

Fosinopril, the only member

Active Sites in ACE

To which angiotensin I or drug binds
Zinc ion (Zn+2) Charged arginine unit (=NH2+) Hydrophobic pocket

General structure of ACE inhibitors


Phosphonic acid Sulfhydryl Carboxylic acid

Alanine Lysine