Scholte H R, Luyt-Houwen I E, Vaandrager-Verduin M H
Department of Biochemistry, Medical Faculty, Erasmus University, Rotterdam, The Netherlands.
Basic Res Cardiol. 1987;82 Suppl 1:63-73. doi: 10.1007/978-3-662-08390-1_8.
The carnitine system functions in the transport of activated acyl groups over the mitochondrial inner membrane, and is needed for oxidation of long-chain fatty acids by all mitochondria. The rate of cardiac fatty acid oxidation is determined by availability of fatty acids, oxygen and the activity of carnitine palmitoyltransferase I, which is regulated by a variety of factors. It is inhibited by malonyl-CoA, which in rat heart was found to be synthesized by acetyl-CoA carboxylase. It is also inhibited by long-chain acylcarnitine. Linoleoylcarnitine was found to be a better inhibitor than palmitoylcarnitine. The concentration of carnitine in human heart, muscle and other tissues is much higher than is needed for the optimal beta-oxidation rate. In contrast to controls, we found in several myopathic patients that extra carnitine (from 1/2 to 5 mM) caused a considerable increase in beta-oxidation rate of isolated muscle mitochondria. In some of these patients we detected medium-chain acyl-CoA dehydrogenase deficiency. Patients with primary carnitine deficiency caused by a renal carnitine leak often show cardiomyopathy, which completely disappears under carnitine therapy. Cardiomyopathy may also be the cause of secondary carnitine deficiency resulting from a mitochondrial defect in acyl-CoA metabolism, or by the mitochondrial defect itself, which may be induced by drugs or viral attack, or be the result of a genetic error. In cardiomyopathic patients with a (subclinical) myopathy, study of isolated mitochondria and homogenate from skeletal muscle may reveal a mitochondrial dysfunction, which, in some patients, is treatable by dietary measures and supplementation with vitamins, CoQ and/or carnitine. When the cause of cardiomyopathy is not known, determination of plasma carnitine and carnitine supplementation of hypocarnitinemic patients is of great therapeutic value.
肉碱系统在活化酰基在线粒体内膜的转运中发挥作用，是所有线粒体氧化长链脂肪酸所必需的。心脏脂肪酸氧化速率取决于脂肪酸的可利用性、氧气以及肉碱棕榈酰转移酶I的活性，该酶受多种因素调节。它受到丙二酰辅酶A的抑制，在大鼠心脏中发现丙二酰辅酶A由乙酰辅酶A羧化酶合成。它也受到长链酰基肉碱的抑制。发现亚油酰肉碱比棕榈酰肉碱是更好的抑制剂。人心脏、肌肉和其他组织中的肉碱浓度远高于最佳β氧化速率所需的浓度。与对照组相比，我们在一些肌病患者中发现，额外的肉碱（从1/2到5 mM）会使分离的肌肉线粒体的β氧化速率显著增加。在其中一些患者中，我们检测到中链酰基辅酶A脱氢酶缺乏。由肾脏肉碱泄漏导致的原发性肉碱缺乏患者常表现出心肌病，在肉碱治疗下可完全消失。心肌病也可能是酰基辅酶A代谢线粒体缺陷或线粒体缺陷本身导致继发性肉碱缺乏的原因，线粒体缺陷可能由药物或病毒攻击诱发，或由基因错误导致。在患有（亚临床）肌病的心肌病患者中，对分离的线粒体和骨骼肌匀浆的研究可能揭示线粒体功能障碍，在一些患者中，可通过饮食措施以及补充维生素、辅酶Q和/或肉碱来治疗。当心肌病的病因不明时，测定血浆肉碱并对低肉碱血症患者补充肉碱具有重要的治疗价值。
