TOXICITY OF CHLOROPHENOLS IN MITOCHONDRIAL MEMBRANES

线粒体内膜氧化磷酸化的研究 线粒体在氯酚的存在下， 辅以对脂质双层膜的研究， 确定氯的毒性的物理化学来源， 酚类。 研究中包含的化合物已被鉴定 作为指定危险物质或同意令污染物的 清洁水法或作为资源中的危险成分 保护和恢复法。 该项目分为两部分：（1） 生物学方面，着重于（a）确定O2消耗量 速率作为氯苯酚分子结构的函数， 浓度，pH值和其他影响静电的因素 相互作用;（B）氯酚对质子泵的影响， 和质子浓度梯度的耗散率; 和（c）反向电子转移。 这些研究将在 细胞、线粒体和亚线粒体颗粒上。 （二） 物理化学，侧重于详细了解 氯代酚类化合物在脂质基质中的作用机制 生物膜 这些研究将包括： zeta电位和吸附等温线，（B）测定 吸附到膜上的氯酚的pKa，（c） 电导率诱导机制的确定 （d）测定氯酚类化合物的 可能与阻塞O2有关的边界电位 （e）表征AHA-复合物作为荷电的 与跨膜相关的膜透性物质 质子的移位，（f）确定凝胶的变化- 脂质膜的流体转变温度作为测量 氯酚诱导的脂质间相互作用的变化，以及 可能的交错和横向分离的探索 脂质。 我们希望识别和描述至少两种类型 构成氯酚毒性作用的贡献： (1)质子电泳，和（2）直接或间接，介导的 膜基质，氯酚与酶的相互作用， 氧化磷酸化反应顺序。

Studies of oxidative phosphorylation in the inner membranes of mitochondria in the presence of chlorinated phenols will be complemented by studies on lipid bilayer membranes in order to determine the physico-chemical origin of the toxicity of chloro- phenols. The compounds included in the study have been identified as Designated Hazardous Substances or Consent Decree Pollutants of the Clean Water Act or as Hazardous Constituents in the Resource Conservation and Recovery Act. The project has two parts: (1) Biological, focused on (a) the determination of the 02 consumption rate as a function of the chlorophenol molecular structure, concentration, the pH, and other factors influencing electrostatic interactions; (b) the effect of chlorophenols on proton pumping, and the rate of dissipation of the proton concentration gradient; and (c) on reverse electron transfer. These studies will be done on cells, mitochondria, and submitochondrial particles. (2) Physico-chemical, focused on detailed understanding of the mechanism of action of chlorinated phenols in the lipid matrix of biomembranes. These studies will include: (a) determination of the zeta potential and adsorption isotherms, (b) determination of the pKalpha of chlorophenols adsorbed to membranes, (c) determination of the mechanism of electrical conductivity induced or modified by chlorophenols, (d) determination of changes of boundary potentials which may be related to blocking of 02 consumption, (e) characterization of AHA- complex as the charged membrane-permeable species associated with transmembrane translocation of protons, (f) determination of changes of the gel- to-fluid transition temperature of lipid membranes as a measure of chlorophenol-induced changes of interlipid interaction, and exploration of possible interdigitation and lateral separation of lipids. We expect to identify and characterize at least two types of contributions constituting the toxic action of chlorophenols: (1) protonophoretic, and (2) direct or indirect, mediated by the membrane matrix, interaction of chlorophenols with enzymes in oxidative phosphorylation sequence of reactions.