Aspirin Hydrolysis in Human and Experimental Animal Plasma and the Effect of Metal Cations on Hydrolase Activities
Aspirin Hydrolysis in Human and Experimental Animal Plasma and the Effect of Metal Cations on Hydrolase Activities
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DOI：
10.1124/dmd.113.051805
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发表时间：
2013-07-01
影响因子：
3.9
通讯作者：
Imai, Teruko
中科院分区：
文献类型：
--
作者：
Bahar, Fatma Goksin;Imai, Teruko
研究了血浆酯酶在人血浆和实验动物血浆中对阿司匹林的水解特性。观察到的阿司匹林水解速率顺序为：兔>人>猴>大鼠>小鼠>狗>小型猪。在人、猴和犬血浆中，阿司匹林被其主要水解酶对氧磷酶（PON）、丁酰胆碱酯酶（BChE）和白蛋白水解。在兔，小鼠和大鼠血浆中，羧酸酯酶（CES）被确定为负责阿司匹林水解的酶，并在小鼠和大鼠血浆中，特别是后者，水解酶活性增加，通过添加乙氧丙嗪，BChE的特异性抑制剂。有趣的是，二价阳离子通过增强或抑制血浆BChE的水解酶活性来影响血浆活性。添加2 mM钙使人、猴和犬血浆中阿司匹林的水解分别增加2.7、1.9和2.3倍。镁也表现出类似但较小的作用。增加钙和镁的浓度导致在人血浆中阿司匹林水解的两个阶段的刺激作用。与此相反，添加锌对血浆BChE活性有抑制作用。据推测，钙和镁结合BChE，从而改变酶的构象，以更适合阿司匹林水解的位置。
The hydrolyzing properties of plasma esterases for aspirin were investigated in human plasma and plasma from experimental animals. The observed rates of aspirin hydrolysis were in the following order: rabbit > human > monkey > rat > mouse > dog > minipig. In human, monkey, and dog plasma, aspirin was hydrolyzed by their major hydrolases, paraoxonase (PON), butyrylcholinesterase (BChE), and albumin. In rabbit, mouse, and rat plasma, carboxylesterase (CES) was determined to be the enzyme responsible for aspirin hydrolysis, and in mouse and rat plasma, especially the latter, hydrolase activity was increased by the addition of ethopropazine, a specific inhibitor of BChE. Interestingly, divalent cations affected the plasma activity by enhancing or inhibiting the hydrolase activity of plasma BChE. The addition of 2 mM calcium increased the hydrolysis of aspirin in human, monkey, and dog plasma by 2.7-, 1.9-, and 2.3-fold, respectively. Magnesium showed a similar but lesser effect. Increasing concentrations of calcium and magnesium resulted in a two-phase stimulatory effect on aspirin hydrolysis in human plasma. In contrast, the addition of zinc had an inhibitory effect on plasma BChE activity. It is postulated that calcium and magnesium bind to BChE and thereby change the conformation of the enzyme to a more appropriate position for aspirin hydrolysis.