Paradies G, Ruggiero F M, Petrosillo G, Quagliariello E
Department of Biochemistry and Molecular Biology, University of Bari, Italy.
Biochim Biophys Acta. 1997 Dec 31;1362(2-3):193-200. doi: 10.1016/s0925-4439(97)00075-6.
Changes in mitochondrial fatty acid metabolism may underlie the decline in cardiac function in the hypothyroid animals. The effect of hypothyroidism on fatty acid oxidation, carnitine-acylcarnitine translocase activity and lipid composition in rat heart mitochondria has been examined. Rates of mitochondrial fatty acid oxidation as well as carnitine-carnitine and carnitine-palmitoylcarnitine exchange reactions were all depressed in heart mitochondria isolated from hypothyroid rats. Kinetic analysis of the carnitine-carnitine exchange reaction showed that the hypothyroid state affects the Vmax of this process, while having no effect on the K(m) value. Heart mitochondrial inner membrane lipid composition was significantly altered in hypothyroid rats. Cardiolipin, particularly, was found to decrease (by around 36%). Alterations in fatty acid pattern of mitochondrial inner membrane preparations from hypothyroid rats were also found. The effects of the hypothyroid state on fatty acids oxidation, carnitine translocase activity and phospholipid composition were completely reversed by following treatment of hypothyroid rats with thyroid hormone. A lower cardiolipin content in the mitochondrial inner membrane offers a plausible mechanism to explain the decline in the translocase activity in hypothyroidism.
线粒体脂肪酸代谢的变化可能是甲状腺功能减退动物心脏功能下降的潜在原因。研究了甲状腺功能减退对大鼠心脏线粒体中脂肪酸氧化、肉碱 - 脂酰肉碱转位酶活性和脂质组成的影响。从甲状腺功能减退大鼠分离的心脏线粒体中，线粒体脂肪酸氧化速率以及肉碱 - 肉碱和肉碱 - 棕榈酰肉碱交换反应均受到抑制。肉碱 - 肉碱交换反应的动力学分析表明，甲状腺功能减退状态影响该过程的最大反应速度（Vmax），而对米氏常数（K(m)值）没有影响。甲状腺功能减退大鼠的心脏线粒体内膜脂质组成发生了显著变化。特别是，发现心磷脂减少（约36%）。还发现甲状腺功能减退大鼠线粒体内膜制剂的脂肪酸模式发生了改变。用甲状腺激素治疗甲状腺功能减退大鼠后，甲状腺功能减退状态对脂肪酸氧化、肉碱转位酶活性和磷脂组成产生的影响完全逆转。线粒体内膜中心磷脂含量较低，为解释甲状腺功能减退中转位酶活性下降提供了一个合理的机制。
