ALUMINUM TOXICITY THROUGH PHOSPHATES

描述：(改编自调查人员的摘要) 从调查员的实验室发表的工作已经建立 至少有一种铝毒的表达方式是通过 与生物磷酸盐形成可溶的铝络合物 这些磷酸盐用作后续工作的底物的能力 酶促反应。主要的表达方式涉及 天然磷镁中镁辅基的置换 作为新陈代谢的中间体的复合体，从而减弱 受体生化途径的活性。《公约》的具体目标 项目是：继续对相互作用的化学研究 A1(III)和生化来源的磷酸盐，集中在关键 膜组分磷酸盐，如磷脂和某些键 磷酸化残基，如肌醇1，4，5-三磷酸；以及 用分子系统Biograf模拟A1-磷酸盐相互作用 计划，目的是阐明 磷-铝和磷-镁络合物。该计划的目的是 模拟实验是为了识别那些能够 阻止有毒物种的形成，从而确定 研究可能会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.