PARADOXICAL ROLE OF LIPID-METABOLISM IN HEART FUNCTION AND DYSFUNCTION
PARADOXICAL ROLE OF LIPID-METABOLISM IN HEART FUNCTION AND DYSFUNCTION
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DOI：
10.1007/bf01270562
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发表时间：
1992-10-21
影响因子：
4.3
通讯作者：
RUPP, H
中科院分区：
文献类型：
--
作者：
DHALLA, NS;ELIMBAN, V;RUPP, H
心脏利用脂肪酸作为底物，而不是葡萄糖来产生能量。心肌摄取和氧化脂肪酸的速率受外源脂肪酸的可获得性、跨线粒体膜的酰基转移速率和柠檬酸循环的乙酰辅酶A氧化速率的控制。肉碱酰辅酶A转移酶在脂肪酸活化和酰基转移与氧化磷酸化的偶联中起着重要作用。活性脂肪酸也被用来合成心肌中的甘油三酯和膜磷脂。抑制长链酰基肉碱转移酶I可以减少脂肪酸的氧化，促进心肌中脂质的合成。在缺血和糖尿病心脏中，脂肪酸及其代谢物如长链酰辅酶A和长链酰基肉碱的积累与心脏功能障碍和细胞损伤有关。膜磷脂组成的改变也被认为改变了各种膜结合酶的活性，从而在不同的病理生理条件下改变了心脏功能。慢性糖尿病被发现与血脂升高、亚细胞缺陷和心脏功能障碍有关。降血脂或减少脂肪酸氧化的药物，如依托莫昔尔，一种棕榈酰肉碱转移酶I的抑制剂，被发现可以促进葡萄糖的利用，并重塑心脏的亚细胞膜细胞器。膜磷脂中的脂肪酸在维持心肌收缩活动的结构完整性和产生能量方面的关键作用，以及脂肪酸及其长链酰基衍生物的毒性作用，支持了心肌中“脂悖论”的概念。
The heart utilizes fatty acids as a substrate in preference to glucose for the production of energy. The rate of fatty acid uptake and oxidation by heart muscle is controlled by the availability of exogenous fatty acids, the rate of acyl translocation across the mitochondrial membrane and the rate of acetyl-CoA oxidation by the citric acid cycle. Carnitine acyl-CoA tranferase appears to have an important function in coupling the fatty acid activation and acyl transfer to the oxidative phosphorylation. Activated fatty acids are also utilized for the synthesis of triglycerides and membrane phospholipids in the myocardium. The inhibition of long chain acyl-carnitine transferase I reduces the oxidation of fatty acids and promotes the synthesis of lipids in the myocardium. Accumulation of fatty acids and their metabolites such as long chain acyl-CoA and long chain acyl-carnitine has been associated with cardiac dysfunction and cell damage in both ischemic and diabetic hearts. Alterations in the composition of membrane phospholipids are also considered to change the activities of various membrane bound enzymes and subsequently heart function under different pathophysiological conditions. Chronic diabetes was found to be associated with increased plasma lipids, subcellular defects and cardiac dysfunction. Lowering the plasma lipids or reducing the oxidation of fatty acids by agents such as etomoxir, an inhibitor of palmitoylcarnitine transferase I was found to promote glucose utilization and remodel the subcellular membranous organelles in the heart. The crucial role of fatty acids in membrane phospholipids for the maintenance of structural integrity and production of energy for cardiac contractile activity as well as the toxic effects of fatty acids and their long chain acyl-derivatives support the concept of 'lipid paradox' in the myocardium.