SMITH J A, DELUCA H F
J Cell Biol. 1964 Apr;21(1):15-26. doi: 10.1083/jcb.21.1.15.
Liver mitochondria isolated in 0.44 M sucrose from rats deficient in essential fatty acids (EFA) oxidized citrate, succinate, alpha-ketoglutarate, glutamate, and pyruvate at a faster rate than did mitochondria isolated from normal rats; however, the oxidation of malate, caprylate, and beta-hydroxybutyrate was not significantly increased. The mitochondria from deficient rats exhibited an increased ATPase activity and extensive structural damage as revealed by electron microscope examination of thin sections. An increase in citrate oxidation and ATPase activity, together with some structural damage, could be demonstrated as early as the 4(th) week in rats on a fat-free diet. Saturated fat in the diet did not prevent the change in mitochondrial structure but accelerated its appearance. Both the biochemical and structural defects could be reversed within three weeks after feeding deficient rats a source of EFA. In the presence of a phosphate acceptor the effect of EFA deficiency on substrate oxidation was largely eliminated. A trend toward a reduced efficiency of oxidative phosphorylation was noted in mitochondria from EFA-deficient rats, but significant uncoupling was found only in the case of citrate, beta-hydroxybutyrate, and glutamate in the presence of malonate. Together with the increased ATPase activity, the uncoupling of phosphorylation could account for the poor respiratory control found with the deficient preparation. However, EFA deficiency was without effect on the respiration of liver slices, which supports the belief that the observed changes in oxidation and phosphorylation are an artifact resulting from damage sustained by the deficient mitochondria during their isolation.
从缺乏必需脂肪酸（EFA）的大鼠中，以0.44M蔗糖分离出的肝脏线粒体，氧化柠檬酸、琥珀酸、α-酮戊二酸、谷氨酸和丙酮酸的速度，比从正常大鼠分离出的线粒体更快；然而，苹果酸、辛酸和β-羟基丁酸的氧化并未显著增加。通过薄切片的电子显微镜检查发现，缺乏EFA的大鼠的线粒体表现出ATP酶活性增加和广泛的结构损伤。早在无脂饮食的大鼠第4周时，就可以证明柠檬酸氧化和ATP酶活性增加，以及一些结构损伤。饮食中的饱和脂肪并不能防止线粒体结构的变化，但会加速其出现。在给缺乏EFA的大鼠喂食EFA来源后三周内，生化和结构缺陷均可逆转。在存在磷酸受体的情况下，EFA缺乏对底物氧化的影响在很大程度上被消除。在来自缺乏EFA的大鼠的线粒体中，注意到氧化磷酸化效率有降低的趋势，但仅在丙二酸存在下，柠檬酸、β-羟基丁酸和谷氨酸的情况下发现明显的解偶联。与增加的ATP酶活性一起，磷酸化的解偶联可以解释缺乏EFA的制剂中发现的呼吸控制不佳的情况。然而，EFA缺乏对肝切片的呼吸没有影响，这支持了一种观点，即观察到的氧化和磷酸化变化是由于缺乏EFA的线粒体在分离过程中受到损伤而产生的假象。
