ALUMINUM TOXICITY THROUGH PHOSPHATES

描述：（改编自研究者摘要） 从研究者的实验室发表的工作，它已经建立 铝毒性表达的至少一种模式是通过 与生物磷酸盐形成可溶性铝络合物， 这些磷酸盐作为随后的底物的能力 酶促反应 主要的表达方式包括 从天然磷镁中置换镁辅因子 复合物，作为代谢的中间体，从而减弱 受体生化途径的活性。 的具体目标 项目是：继续化学研究之间的相互作用 A1（III）和生物化学来源的磷酸盐，集中在关键 膜组分磷酸盐，如磷脂，和某些关键 磷酸化残基，如1，4，5-三磷酸肌醇;和 使用Molecular Systems BIOGRAF建立A1-磷酸相互作用模型 程序，目的是阐明精确的特征， 磷-铝和磷-镁络合物。 的目的 模拟实验是为了确定那些能够 阻止有毒物质的形成，从而确定 研究可能导致有效的治疗方案。

DESCRIPTION: (Adapted from the investigator's abstract) In previous published work from the investigator's laboratory it has been established that at least one mode of aluminum toxic expression is through the formation of soluble aluminum complexes with biophosphates that compromises the ability of these phosphates to serve as substrates for subsequent enzymatic reactions. The principal mode of expression involves the displacement of the magnesium cofactor from the natural phosphomagnesium complexes that serve as intermediates of metabolism, thus attenuating the activity of the recipient biochemical pathway. The specific aims of the project are to:continue chemical investigation of the interactions between A1(III) and phosphates of biochemical origin, concentrating on key membrane-component phosphates, such as the phospholipids, and certain key phosphorylated residues, such as myo-inositol 1,4,5-trisphosphate; and model A1-phosphate interactions using the Molecular Systems BIOGRAF program, with the goal of elucidating the precise characteristics of phospho-aluminum and phospho-magnesium complexes. The purpose of the modeling experiments is to identify those ionic systems capable of interdicting the formation of toxic species, thus identifying avenues of research likely to lead toward effective therapeutic regimens.