FATTY ACID INTERACTIONS IN THE HEART

这个项目是针对一般问题的 脂类在细胞内的运动。重点是理解 心脏中脂肪酸运动和代谢的调节 组织，并确定这一规定是如何在 已知的影响心脏功能的情况。具体的 重点是脂肪酸结合蛋白的潜在作用。 (FABP)在影响心脏脂肪酸代谢中的作用。这个 具体目标是：1)研究 大鼠心脏FABP上的配基结合部位。结合分析、核磁共振和 将采用化学修饰来关联 具有结构性变化的约束力。2)确定FABP是否起作用 在细胞内结合和运输脂肪酸，酰基辅酶A和 酰基卡尼汀。含有带有酶的细胞器的体外系统 将开发利用这些物质。3)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。加碘的FABP将用于 与分离的细胞膜或合成材料结合的试验 泡囊制剂。4)确定金额的变化或 大鼠心脏FABP的分布是由于转录或后转录引起的 转录控制。5)使用培养的新生儿细胞或细胞 成人心肌细胞悬液用于调节因子的研究 FABP营业额。希望通过了解老鼠的心脏是如何 FABP在心脏脂质正常调节中的作用 新陈代谢，正常功能的改变可能会 在某些疾病状态下可以检查是一个致病因素。

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.