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TOXICITY OF CHLOROPHENOLS IN MITOCHONDRIAL MEMBRANES

氯酚对线粒体膜的毒性

基本信息

批准号：
3253461
负责人：
Pavel K Smejtek
金额：
$ 13.93万
依托单位：
PORTLAND STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-07-01 至 1992-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3253461
关键词：
adenosine triphosphate chlorine electrodes electron transport electrophoresis electrophysiology environmental toxicology enzyme mechanism laboratory rat mathematical model membrane activity membrane lipids membrane potentials membrane structure mitochondrial membrane oxidative phosphorylation phenols toxicant interaction

项目摘要

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.

猪内膜氧化磷酸化的研究线粒体在氯化苯酚存在的情况下会辅以对脂类双层膜的研究，以便确定氯仿毒性的物理化学来源酚类。研究中包含的化合物已被确定作为指定的危险物质或同意法令污染物《清洁水法》或资源中的有害成分《保护和恢复法案》。该项目分为两部分：(1) 生物学，重点是(A)02消费量的测定速率作为氯苯酚分子结构的函数，浓度、pH等影响静电的因素相互作用；(B)氯酚对质子泵的影响，以及质子浓度梯度的消散率；和(C)反向电子转移。这些研究将会完成在细胞、线粒体和亚线粒体颗粒上。(2) 物理化学，重点是详细了解氯代酚在大鼠脂基质中的作用机理生物膜。这些研究将包括：(A)确定 Zeta电位和吸附等温线，(B)测定膜上吸附的氯苯酚的pKalpha，(C) 感生电导机理的确定或用氯苯酚修饰，(D)测定可能与02阻塞有关的边界势消耗，(E)带电的AHA络合物的表征与跨膜有关的膜透性物种质子的移位，(F)凝胶变化的测定- 脂膜向流体的转变温度作为衡量氯苯酚引起的脂间相互作用的改变可能的交错和侧向分离的探讨脂类。我们希望确定和描述至少两种类型构成氯苯酚毒性作用的成分： (1)原基渗透，以及(2)直接或间接，由膜基质，氯代酚与酶的相互作用氧化磷酸化反应序列。