PDF(Pubmed)
Abstract：
The most favorable targets for retrospectively determining human exposure to organophosphorus pesticides, insecticides, retardants, and other industrial organophosphates (OPs) are adducts of OPs with blood plasma butyrylcholinesterase (BChE) and human serum albumin (HSA). One of the methods for determining OP exposure is the reactivation of modified BChE using a concentrated solution of KF in an acidic medium. It is known that under the action of fluoride ion, OPs or their fluoroanhydrides can be released not only from BChE adducts but also from the adducts with albumin; however, the contribution of albumin to the total pool of released OPs after plasma treatment with KF has not yet been studied. The efficiency of OP release can be affected by many factors associated with the experimental technique, but first, the structure of the adduct must be taken into account. We report a comparative analysis of the structure and conformation of organophosphorus adducts on HSA and BChE using molecular modeling methods and the mechanism of OP release after fluoride ion exposure. The conformational analysis of the organophosphorus adducts on HSA and BChE was performed, and the interaction of fluoride ions with modified proteins was studied by molecular dynamics simulation. The geometric and energy characteristics of the studied adducts and their complexes with fluoride ion were calculated using molecular mechanics and semiempirical approaches. The structural features of modified HSA and BChE that can affect the efficiency of OP release after fluoride ion exposure were revealed. Using the proposed approach, the expediency of using KF for establishing exposure to different OPs, depending on their structure, can be assessed.
摘要：
回顾性测定人类有机磷农药暴露的最有利目标，杀虫剂,阻燃剂，和其他工业有机磷酸盐（OPs）是OPs与血浆丁酰胆碱酯酶（BChE）和人血清白蛋白（HSA）的加合物。确定OP暴露的方法之一是使用酸性介质中的KF浓溶液重新活化改性的BChE。众所周知，在氟离子的作用下，OPs或它们的氟酸酐不仅可以从BChE加合物中释放出来，也可以从与白蛋白的加合物中释放出来；然而，尚未研究用KF进行血浆治疗后白蛋白对总释放OPs的贡献.OP释放的效率可能受到与实验技术相关的许多因素的影响。但首先,必须考虑加合物的结构。我们报告了使用分子建模方法对HSA和BChE上有机磷加合物的结构和构象进行的比较分析，以及氟离子暴露后OP释放的机理。对HSA和BChE上的有机磷加合物进行了构象分析，分子动力学模拟研究了氟离子与修饰蛋白的相互作用。使用分子力学和半经验方法计算了所研究的加合物及其与氟离子的配合物的几何和能量特性。揭示了改性HSA和BChE的结构特征，这些结构特征可以影响氟离子暴露后OP的释放效率。使用所提出的方法，使用KF建立不同OPs暴露的权宜之计，根据它们的结构，可以评估。
