Captopril inhibits peptidylglycine- alpha-hydroxylating monooxygenase: implications for therapeutic effects.
Captopril inhibits peptidylglycine- alpha-hydroxylating monooxygenase: implications for therapeutic effects.
复制标题
卡托普利抑制肽基甘氨酸-α-羟基化单加氧酶：对治疗效果的影响。
DOI：
10.1159/000028290
复制
发表时间：
1999
期刊：
影响因子：
3.1
通讯作者：
Mueller,GP
中科院分区：
文献类型：
--
作者：
Mueller,SA;Driscoll,WJ;Mueller,GP
巯甲丙脯酸的治疗作用通过其巯基部分促进，巯基部分与血管紧张素转化酶（ACE; EC 3.4.15.1）的金属（Zn 2+）辅基相互作用。本研究的重点是卡托普利作为另一种金属依赖性（Cu 2+）酶肽基甘氨酸-α-羟基化单加氧酶（PHM; EC 1.14.17.3）的抑制剂。PHM在α-酰胺化中是限速的，α-酰胺化是一种生物激活几种升压肽的COOH末端修饰。Captopril在体外以剂量依赖性方式抑制PHM，IC 50约为100 μmol/l。这种抑制作用可通过增加Cu 2+浓度而部分逆转。结构相似的非巯基ACE抑制剂不影响PHM的活性。目前的研究结果表明，巯甲丙脯酸的治疗效果可能是由于一系列的金属酶，包括ACE和PHM的行动。
The therapeutic actions of captopril are facilitated by its sulfhydryl moiety which interacts with the metal (Zn2+) prosthetic groups of angiotensin-converting enzyme (ACE; EC 3.4.15.1). This study focused on captopril as an inhibitor of another metal-dependent (Cu2+) 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 IC50of approximately 100 μmol/l. This inhibition was partially reversed by increased concentrations of Cu2+. 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.