FATTY ACID INTERACTIONS IN THE HEART

这个项目是针对一般问题， 脂质的细胞内运动。 重点在于理解 心脏脂肪酸运动和代谢的调节 组织，并确定这种调节是如何改变的， 已知会影响心脏功能的疾病。 具体 重点是脂肪酸结合蛋白的潜在作用 脂肪酸结合蛋白（FABP）影响心脏脂肪酸代谢。 的 具体目标是：1）研究的性质和特殊性， 大鼠心脏FABP上的配体结合位点。 结合试验、NMR和 化学修饰将被用来关联 结合结构变化。 2)为了确定FABP是否起作用， 在细胞内结合和转运脂肪酸、酰基辅酶A和 酰基肉毒碱 含有细胞器和酶的体外系统 将开发利用这些物质。 3)以确定是否 心脏或肝脏FABP与模型膜上的特定位点相互作用 系统或生物膜。 碘化FABP将用于 与分离细胞膜或合成细胞膜结合试验 囊泡制剂。 4)以确定金额或 大鼠心脏FABP的分布是由于转录或后 转录调控 5)使用培养的新生细胞或细胞 成人心肌细胞悬液，用于研究 FABP周转率。 希望通过了解老鼠的心脏 脂肪酸结合蛋白在心脏脂质正常调节中的作用 代谢，正常功能的改变可能 在某些疾病状态下，可以检查致病因素。

This project is directed towards the general problem of intracellular movement of lipids. The focus is on understanding the regulation of fatty acid movement and metabolism in cardiac tissue, and to determine how this regulation is altered in conditions known to affect cardiac performance. The specific emphasis is on the potential role of fatty acid binding protein (FABP) in influencing fatty acid metabolism in the heart. The specific aims are: 1) To-study the nature and specificity of the ligand binding sites on rat heart FABP. Binding assays, NMR, and chemical modification will be employed to correlate changes in binding with structural changes. 2) To determine if FABP functions in intracellular binding and transport of fatty acid, acyl CoA and acylcarnitine. In vitro systems containing organelles with enzymes utilizing those substances will be developed. 3) To determine if heart or liver FABP interacts with specific sites on model membrane systems or biological membranes. Iodinated FABP will be used to test for binding to isolated cellular membranes or synthetic vesicle preparations. 4) To determine if changes in amount or distribution of rat heart FABP are due to transcriptional or post- transcriptional control. 5) To use cultured neonatal cells or cell suspensions from adult myocytes for studies on factors regulating FABP turnover. It is hoped that by understanding how rat heart FABP functions in the normal regulation of cardiac lipid metabolism, the possibility that alterations in normal function may be a causative factor in certain disease states can be examined.