LONG CHAIN ACYL COA INTERACTIONS IN THE HEART

脂代谢异常被认为是一种 在心肌缺血期间发生细胞损伤的因素。 长链酰基辅酶A衍生物已被证明在心脏中积累 组织在缺血期间，并可能与细胞内的不利相互作用 膜，产生功能变化。这项提议旨在 获得关于长链酰基CoA与其相互作用的新信息 从心脏组织中提取膜并确定这种相互作用如何 影响细胞内脂质代谢。这样做的长期目标是 建议确定在酰基辅酶A膜上获得的数据 相互作用符合长链酰基辅酶A的假设 分子确实会在心脏组织中造成膜损伤 缺血症。具体目标是：1.研究酰基的相互作用 辅酶A与磷脂双层在体外。单层磷脂小泡 将被用作模型体系以及表面电荷、化学物质的影响 囊泡的组成和物理状态将被确定。2.)至 直接研究酰化辅酶A与胞内膜的相互作用 来自心脏组织。肌浆网和内部线粒体 将使用膜并开发一种检测系统来确定 表面相互作用、特异度和效应的动力学 膜的改性。此外，酰基CoA有可能 改变与分离的 细胞器将接受测试。3.)以确定存在一种可溶的 大鼠或兔心脏中与酰辅酶A结合的蛋白质，为了纯化该蛋白质， 并对结合的性质进行表征。4.)美国政府的影响 可溶性酰基辅酶A结合蛋白与乙酰辅酶A相互作用的研究 将测定单层囊泡和离体膜，并 结合蛋白可能促进运输或代谢的可能性 将进行酰基辅酶A的测试。

Abnormalities of lipid metabolism have been implicated as a causative factor for the cellular damage that occurs during myocardial ischemia. Long chain acyl CoA derivatives have been shown to accumulate in heart tissue during ischemia and may interact adversely with intracellular membranes, producing functional changes. This proposal is designed to obtain new information on the interaction of long chain acyl CoA with membranes from cardiac tissue and to determine how such interactions might influence intracellular lipid metabolism. The long term objective of this proposal is to determine if the data obtained on acyl CoA-membrane interactions are consistent with the hypothesis that long chain acyl CoA molecules actually do cause membrane damage in cardiac tissue during ischemia. The specific aims are: 1.) To examine the interaction of acyl CoA with phospholipid bilayers in vitro. Unilamellar phospholipid vesicles will be used as a model system and the effects of surface charge, chemical composition and physical state of the vesicles will be determined. 2.) To study directly the interaction of acyl CoA with intracellular membranes from cardiac tissue. Sarcoplasmic reticulum and inner mitochondrial membrane will be used and an assay system developed to determine the kinetics of the interaction, specificity, and effects of surface modification of the membranes. In addition, the possibility that acyl CoA alters the activity of selected enzymes associated with the isolated organelles will be tested. 3.) To establish the presence of a soluble protein in rat or rabbit heart that binds acyl CoA, to purify the protein, and to characterize the nature of the binding. 4.) The effect of the soluble acyl CoA binding protein on the interaction of acyl CoA with unilamellar vesicles and isolated membranes will be determined and the possibility that the binding protein may facilitate transport or metabolism of acyl CoA will be tested.