Enalapril is an anti-hypertension "prodrug" (i.e., a drug precursor) that is inactive until the ethyl ester (arrow in figure) is hydrolyzed by esterases pre-sent in blood plasma. The active drug is the dicarboxylic acid ("enalaprilat") that results from this hydrolysis reaction.
a. Enalapril is administered in pill form, but enalaprilat must be administered intravenously. Why do you suppose enalapril works as a pill, but enalaprilat does not?

b. Enalaprilat is a competitive inhibitor of the angiotensin-converting enzyme (ACE), which cleaves the blood-pressure regulating peptide angiotensin I. ACE has a KM = 52 μM for angiotensin I, which is present in plasma at a concentration of 75 μM. When enalaprilat is present at 2.4 nM, the activity of ACE in plasma is 10% of its uninhibited activity. What is the value of KI for enalaprilat?

Transcribed Image Text:

EtOO CH3 HOOC Enalapril