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Captopril Inhibits Peptidylglycine- α-Hydroxylating Monooxygenase: Implications for Therapeutic Effects

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The therapeutic actions of captopril are facilitated by its sulfhydryl moiety which interacts with the metal (Zn<sup>2+</sup>) prosthetic groups of angiotensin-converting enzyme (ACE; EC 3.4.15.1). This study focused on captopril as an inhibitor of another metal-dependent (Cu<sup>2+</sup>) enzyme, peptidylglycine-α-hydroxylating monooxygenase (PHM; EC 1.14.17.3). PHM is rate limiting in α-amidation, a COOH-terminal modification that bioactivates several pressor peptides. Captopril inhibited PHM in vitro in a dose-dependent manner with an IC<sub>50</sub> of approximately 100 μmol/l. This inhibition was partially reversed by increased concentrations of Cu<sup>2+</sup>. Structurally similar nonsulfhydryl ACE inhibitors did not affect the activity of PHM. The present findings indicate that the therapeutic effectiveness of captopril may result from actions on a range of metalloenzymes including ACE and PHM.
Title: Captopril Inhibits Peptidylglycine- α-Hydroxylating Monooxygenase: Implications for Therapeutic Effects
Description:
The therapeutic actions of captopril are facilitated by its sulfhydryl moiety which interacts with the metal (Zn<sup>2+</sup>) prosthetic groups of angiotensin-converting enzyme (ACE; EC 3.
4.
15.
1).
This study focused on captopril as an inhibitor of another metal-dependent (Cu<sup>2+</sup>) enzyme, peptidylglycine-α-hydroxylating monooxygenase (PHM; EC 1.
14.
17.
3).
PHM is rate limiting in α-amidation, a COOH-terminal modification that bioactivates several pressor peptides.
Captopril inhibited PHM in vitro in a dose-dependent manner with an IC<sub>50</sub> of approximately 100 μmol/l.
This inhibition was partially reversed by increased concentrations of Cu<sup>2+</sup>.
Structurally similar nonsulfhydryl ACE inhibitors did not affect the activity of PHM.
The present findings indicate that the therapeutic effectiveness of captopril may result from actions on a range of metalloenzymes including ACE and PHM.

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