REGULATION OF MYOCARDIAL FATTY ACID METABOLISM

在本申请中提出的研究是针对确定 全面控制心肌中的脂肪酸代谢。 一个主要部分 工作的一部分是关于确定控制机制， 辅酶A和肉毒碱的组织水平，脂肪的必需辅助因子 酸代谢 辅酶A合成的速率控制步骤 泛酸将通过测量合成速率来测定， 使用灌注心脏的途径中中间体的组织水平， 分离的线粒体。 当这些步骤被确定后， 催化反应将被分离， 将在体外测定。 肉毒碱不是由心脏合成的 肌肉. 控制肉毒碱的跨膜转运将 在心里面决定。 细胞质和线粒体的作用 辅酶A和肉毒碱水平在控制脂肪酸代谢中的作用 将在灌注的心脏中测定，其中这些组织水平 辅因子可以改变。 乳酸盐抑制脂肪酸氧化， 这种效应的机制尚不清楚。 乳酸增加的假设 心肌中丙二酰辅酶A的水平，其抑制外线粒体 将在灌注的大鼠心脏中研究肉毒碱酰基CoA转移酶。

The studies proposed in this application are directed toward detemining the overall control of fatty acid metabolism in cardiac muscle. A major part of the work is concerned with determining the mechanism of control of tissue levels of coenzyme A and carnitine, essential cofactors for fatty acid metabolism. The rate controlling steps for coenzyme A synthesis from pantothenic acid will be determined by measuring rates of synthesis and tissue levels of intermediates in the pathway using the perfused heart and isolated mitochondria. When these steps are identified, the enzymes catalyzing the reactions will be isolated and regulation of this activity will be determined in vitro. Carnitine is not synthesized by cardiac muscle. The control of carnitine transport across the plasma membrane will be determined in perfused hearts. The role of cytosolic and mitochondrial levels of coenzyme A and carnitine in controlling fatty acid metabolism will be determined in perfused hearts where the tissue levels of these cofactors can be altered. Lactate inhibits fatty acid oxidation and the mechanism of this effect is unknown. The hypothesis that lactate increases myocardial levels of malonyl CoA which inhibits the outer mitochondrial carnitine-acyl CoA transferase will be investigated in perfused rat hearts.