Department of Biology, Faculty of Science and Literature, Balikesir University , Balikesir , Turkey.
J Enzyme Inhib Med Chem. 2015 Apr;30(2):245-9. doi: 10.3109/14756366.2014.913038. Epub 2014 Jun 17.
Human serum paraoxonase (PON1, EC 3.1.8.1.) is a high-density lipid (HDL)-associated, calcium-dependent enzyme. In this study, the effects of Haloperidol, Fluoxetine hydrochloride, Diazepam and Acepromazine drugs used for the therapy of antidepressant and antipsychotic diseases, on paraoxonase enzyme activity was studied in in vitro inhibition studies on purified human serum PON1. PON1 enzyme was purified from human blood using two-step procedures, namely, ammonium sulfate precipitation and sepharose-4B-l-tyrosine-1-napthylamine hydrophobic interaction chromatography. The overall purification of human serum PON1 was obtained in a activity of 109.29 U/mL and this enzyme was purified 125-fold. The SDS-polyacrylamide gel electrophoresis of the enzyme indicates a single band with an apparent MW of 43 kDa. Inhibition studies indicated that haloperidol and fluoxetine hydrocloride were effective inhibitors on purified human serum PON1 activity with IC50 of 0.187 and 3.08 mM values, respectively. The kinetics of interaction of haloperidol and fluoxetine hydrocloride with the purified human serum PON1 indicated uncompetitive inhibiton pattern with Ki of 4.15 and 0.007 mM, respectively.
人血清对氧磷酶（PON1，EC 3.1.8.1.）是一种高密度脂蛋白（HDL）相关的、依赖钙的酶。在这项研究中，研究了用于治疗抗抑郁和抗精神病疾病的氟哌啶醇、盐酸氟西汀、地西泮和乙酰丙嗪药物对体外纯化人血清 PON1 的抑制作用。使用两步程序，即硫酸铵沉淀和 sepharose-4B-l-酪氨酸-1-萘胺疏水性相互作用色谱法，从人血中纯化 PON1 酶。人血清 PON1 的总纯化度为 109.29 U/mL，该酶纯化了 125 倍。酶的 SDS-聚丙烯酰胺凝胶电泳显示出一条具有 43 kDa 明显 MW 的单带。抑制研究表明，氟哌啶醇和盐酸氟西汀是对纯化的人血清 PON1 活性的有效抑制剂，其 IC50 值分别为 0.187 和 3.08 mM。氟哌啶醇和盐酸氟西汀与人血清 PON1 的相互作用动力学表明，Ki 值分别为 4.15 和 0.007 mM，呈非竞争性抑制模式。
