Mechanism of coumarin action: sensitivity of vitamin K metabolizing enzymes of normal and warfarin-resistant rat liver.
Mechanism of coumarin action: sensitivity of vitamin K metabolizing enzymes of normal and warfarin-resistant rat liver.
复制标题
香豆素作用机制：正常和华法林耐药大鼠肝脏维生素 K 代谢酶的敏感性。
DOI：
10.1021/bi00539a020
复制
发表时间：
1982
期刊：
影响因子：
2.9
通讯作者：
Suttie,JW
中科院分区：
文献类型：
--
作者：
Hildebrandt,EF;Suttie,JW
E. F. Hildebrandt 和 J. W. Suttie* 摘要：已经确定了两种香豆素抗凝剂华法林和地芬那古对正常大鼠和华法林耐药品系大鼠肝脏微粒体维生素 K 依赖性羧化酶、维生素 K 环氧化酶、维生素 K 环氧化物还原酶和胞质维生素 K 还原酶 (DT-dia-phorase) 的体外影响。抑制两种大鼠品系的羧化酶和环氧酶活性都需要毫摩尔浓度的两种香豆素。当使用可溶性或脂质体相关底物时，DT-心肌黄酶对香豆素抑制的敏感性有所不同，但心肌黄酶维生素 K 是微粒体蛋白前体中特定谷氨酰残基到凝血因子 II、VII、IX 和 X 以及其他维生素 K 依赖性蛋白的核糖体后羧化所必需的（Suttie，1980a）。这种微粒体羧化酶需要“CO2”、02、谷氨酰底物和对苯二酚形式的维生素 K (Suttie, 1980b, c)。相同的粗制微粒体
E. F. Hildebrandt and J. W. Suttie* abstract: The in vitro effects of two coumarin anticoagulants, warfarin and difenacoum, on rat liver microsomalvitamin K dependent carboxylase, vitamin K epoxidase, vitamin K epoxide reductase, and cytosolicvitamin K reductase (DT-dia-phorase) from the livers of normal and a warfarin-resistant strain of rats have been determined. Millimolar concentrations of both coumarins are required to inhibit the carboxylase and epoxidase activities in both strains of rats. Sensitivity of DT-diaphorase to coumarin inhibition differs when a soluble or liposomal-associated substrate is used, but thediaphorasesVitamin K is required for the postribosomal carboxylation of specific glutamyl residues to-carboxyglutamyl residues in microsomal protein precursors to clotting factors II, VII, IX, and X, as well as other vitaminK dependent proteins (Suttie, 1980a). This microsomal carboxylase requires “C02”, 02, a glutamyl substrate, and the hydroquinone formof vitamin K (Suttie, 1980b, c). The same crude microsomal