Beydemir Şükrü, Demir Yeliz
Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, 26470, Turkey.
Department of Chemistry, Faculty of Sciences, Atatürk University, Erzurum, 25240, Turkey.
J Biochem Mol Toxicol. 2017 Jun;31(6). doi: 10.1002/jbt.21889. Epub 2016 Dec 29.
Serum paraoxonase (PON1) is a key enzyme related to high-density lipoprotein (HDL)-cholesterol particle. It can prevent the oxidation of low-density lipoprotein (LDL) and HDL. The present article focuses on the in vitro inhibition role of some antiepileptic drugs (AEDs) such as valproic acid, gabapentin, primidone, phenytoin, and levetiracetam on human paraoxonase (hPON1). Therefore, PON1 was purified from human serum with a specific activity of 3976.36 EU/mg and 13.96% yield by using simple chromatographic methods. The AEDs were tested at various concentrations, which showed reduced in vitro hPON1 activity. IC values for gabapentin, valproic acid, primidone, phenytoin, and levetiracetam were found to be 0.35, 0.67, 0.87, 6.3, and 53.3 mM, respectively. K constants were 0.261 ± 0.027, 0.338 ± 0.313, 0.410 ± 0.184, 10.3 ± 0.001, and 43.01 ± 0.003 mM, respectively. Gabapentin exhibited effective inhibitory activity as compared with the other drugs. The inhibition mechanisms of all compounds were noncompetitive.
血清对氧磷酶（PON1）是一种与高密度脂蛋白（HDL）胆固醇颗粒相关的关键酶。它可以防止低密度脂蛋白（LDL）和HDL的氧化。本文重点研究了丙戊酸、加巴喷丁、扑米酮、苯妥英和左乙拉西坦等抗癫痫药物（AEDs）对人对氧磷酶（hPON1）的体外抑制作用。因此，采用简单的色谱方法从人血清中纯化出PON1，比活性为3976.36 EU/mg，产率为13.96%。对AEDs进行了不同浓度的测试，结果显示其体外hPON1活性降低。加巴喷丁、丙戊酸、扑米酮、苯妥英和左乙拉西坦的IC值分别为0.35、0.67、0.87、6.3和53.3 mM。K常数分别为0.261±0.027、0.338±0.313、0.410±0.184、10.3±0.001和43.01±0.003 mM。与其他药物相比，加巴喷丁表现出有效的抑制活性。所有化合物的抑制机制均为非竞争性。
