Question

2. Captopril was the first of a class of blood-pressure lowering drugs that work by reversibly inhibiting Angiotension-converting enzyme (ACE). Later to the market was Lisinopril. This class of drugs is the fifth most prescribed, approaching 200 million prescriptions per year in the US alone. ACE inhibitors work by preventing the proteolytic cleavage of angiotensin I by ACE to create its active form angiotensin II, which binds to receptors in the walls of blood vessels to initiate their relaxation, reducing hypertension. The data in the table below represent a kinetic analysis of human ACE activity in the absence and presence of 50 nM Captopril, 50 nM Lisinopril, and a fraction of blood serum that passed through a 100 kD pore-size filter but was retained by a 50 kD pore-sized filter during ultrafiltration. ACE activity was followed photometrically using the artificial substrate FAPGG, (N-(3-(2- furyl)acryloyl]-L-phenylalanylglycylglycine, which absorbs at 340 nm. Cleavage by ACE eliminates the absorbance. Reaction mixtures contained FAPGG, 300 mM NaCl, 10 uM ZnCl2, 25 mM HEPES, pH 8.2, plus ACE. Incubation was at 37° C.