Wilson Christina R, Sauer John-Michael, Carlson Gary P, Wallin Reidar, Ward Michael P, Hooser Stephen B
Animal Disease Diagnostic Laboratory, Purdue University, 1175 ADDL, 460 South University, West Lafayette, IN 47907-2065, USA.
Toxicology. 2003 Aug 1;189(3):191-8. doi: 10.1016/s0300-483x(03)00133-1.
A comparative study of vitamin K(1) 2,3-epoxide reductase (VKOR) activity in vitro was conducted across species. The apparent kinetic constants K(m app), V(max), and Cl(int app) were determined in bovine, canine, equine, human, murine, ovine, porcine, and rat hepatic microsomes. In addition to these enzyme kinetic constants, the IC(50) of warfarin for VKOR was determined in human, murine, porcine, and rat hepatic microsomes. Interspecies differences were observed when comparing the K(m app) (range, 2.41-6.46 microM), V(max) (range, 19.5-85.7 nmol/mg/min), and Cl(int app) (range, 8.2-18.4 ml/mg/min) values. Comparison of the IC(50) values of warfarin, across the four species tested, revealed a significant species difference between murine microsomes (0.17 microM) and rat microsomes (0.07 microM). Overall, this study indicates that there are interspecies differences regarding the in vitro reduction of vitamin K(1) 2,3-epoxide by the warfarin-sensitive enzyme vitamin K(1) 2,3-epoxide reductase. Significant differences between the IC(50) values of murine and rat microsomes suggest differences in the susceptibility of these species to warfarin.
开展了一项跨物种的维生素K(1) 2,3-环氧化物还原酶（VKOR）体外活性比较研究。在牛、犬、马、人、小鼠、绵羊、猪和大鼠的肝微粒体中测定了表观动力学常数K(m app)、V(max)和Cl(int app)。除了这些酶动力学常数外，还在人、小鼠、猪和大鼠的肝微粒体中测定了华法林对VKOR的IC(50)。比较K(m app)（范围为2.41 - 6.46 microM）、V(max)（范围为19.5 - 85.7 nmol/mg/min）和Cl(int app)（范围为8.2 - 18.4 ml/mg/min）值时观察到种间差异。比较所测试的四个物种的华法林IC(50)值，发现小鼠微粒体（0.17 microM）和大鼠微粒体（0.07 microM）之间存在显著的物种差异。总体而言，本研究表明，华法林敏感的酶维生素K(1) 2,3-环氧化物还原酶在体外还原维生素K(1) 2,3-环氧化物方面存在种间差异。小鼠和大鼠微粒体IC(50)值之间的显著差异表明这些物种对华法林的敏感性存在差异。
