Nozu F, Takeyama N, Tanaka T
Department of Emergency and Critical Care Medicine, Kansai Medical University, Osaka, Japan.
Hepatology. 1992 Jun;15(6):1099-106. doi: 10.1002/hep.1840150621.
Hepatic mitochondrial functions related to fatty acid metabolism, including the respiratory control ratio, fatty acid oxidative capacity and carnitine palmitoyltransferase I activity, were studied in vitro with mitochondria isolated from rats treated with thioacetamide for up to 12 wk. The levels of ketone bodies, carnitine, carnitine esters and malonyl-coenzyme A were also determined in liver extracts. Polarography of mitochondrial respiration from succinate or glutamate plus malate showed a lower respiratory control ratio in thioacetamide-treated rats, whereas uncoupled oxygen consumption was not altered. This suggests that the mitochondrial respiratory chain capacity remained intact in the thioacetamide-treated rats. The oxygen consumption associated with palmitoyl-coenzyme A and palmitoyl-L-carnitine oxidation by isolated liver mitochondria was increased by thioacetamide treatment on both a per-mitochondrial protein and a per-total liver basis. The carnitine palmitoyl-transferase I activity; the tissue levels of ketone bodies, carnitine and carnitine esters; and the beta-hydroxybutyrate/acetoacetate ratio were all higher in the livers of thioacetamide-treated animals than in control livers, whereas the hepatic malonyl-coenzyme A level was decreased by thioacetamide. These results indicate the increased diversion of cytosolic long-chain acyl-coenzyme As into the mitochondria for beta-oxidation rather than their esterification and use in lipogenesis. These intrahepatic metabolic changes induced by chronic thioacetamide administration may reflect the whole-body catabolic state and can be seen as adaptive for maintaining energy homeostasis under conditions of impaired glucose tolerance.
利用从用硫代乙酰胺处理长达12周的大鼠分离得到的线粒体，在体外研究了与脂肪酸代谢相关的肝线粒体功能，包括呼吸控制率、脂肪酸氧化能力和肉碱棕榈酰转移酶I活性。还测定了肝脏提取物中酮体、肉碱、肉碱酯和丙二酰辅酶A的水平。琥珀酸或谷氨酸加苹果酸引起的线粒体呼吸极谱分析显示，硫代乙酰胺处理的大鼠呼吸控制率较低，而解偶联氧消耗未改变。这表明硫代乙酰胺处理的大鼠线粒体呼吸链能力保持完整。硫代乙酰胺处理使分离的肝线粒体与棕榈酰辅酶A和棕榈酰-L-肉碱氧化相关的氧消耗在每线粒体蛋白和每全肝基础上均增加。硫代乙酰胺处理动物肝脏中的肉碱棕榈酰转移酶I活性、酮体、肉碱和肉碱酯的组织水平以及β-羟基丁酸/乙酰乙酸比值均高于对照肝脏，而硫代乙酰胺使肝脏丙二酰辅酶A水平降低。这些结果表明，胞质长链酰基辅酶A更多地转向线粒体进行β氧化，而不是酯化并用于脂肪生成。慢性给予硫代乙酰胺引起的这些肝内代谢变化可能反映了全身分解代谢状态，并且可被视为在葡萄糖耐量受损的情况下维持能量稳态的适应性变化。
