Hörl W H, Kittel R, Heidland A
Am J Clin Nutr. 1980 Jul;33(7):1468-75. doi: 10.1093/ajcn/33.7.1468.
Binephrectomized rats treated with high doses of ketoleucine (0.5 g/rat per 20 hr) expired after about 45 hr. In contrast, survival time was 100% 60 hr after ureteral ligation. In comparison to animals receiving low-protein diets, addition of leucine to the diet almost doubled muscle and liver protein content whereas ketoleucine increased liver protein during the first 40 hr after operation about 1.5-fold. Skeletal muscle protein content was enhanced in the ureter-ligated rats with administration of ketoleucine. There was also about a 10-fold elevation in liver glycogen and total carbohydrate content between the 20th and 60th hr in binephrectomized rats fed leucine at 5-hr intervals. In skeletal muscle glycogen, there were no significant differences among the acutely uremic rats fed at 10-hr intervals low-protein diets alone or supplemented with leucine or ketoleucine. Leucine inhibits glycogenolysis by lowering phosphorylase alpha activity in muscle and liver, whereas ketoleucine enhances glycogenolysis in acute uremia. In rats supplemented with letoleucine, there is a progressive inactivation of glycogen synthetase I which occurs in parallel with increasing phosphorylase alpha activity. In binephrectomized rats receiving leucine supplements at 5-hr feeding intervals, the activity of liver glycogen synthetase I increases up to a maximum of 90% of total enzyme activity.
接受高剂量酮亮氨酸（每20小时0.5克/只大鼠）治疗的双侧肾切除大鼠在约45小时后死亡。相比之下，输尿管结扎术后60小时的存活率为100%。与接受低蛋白饮食的动物相比，在饮食中添加亮氨酸几乎使肌肉和肝脏蛋白质含量增加了一倍，而酮亮氨酸在术后最初40小时内使肝脏蛋白质增加了约1.5倍。给予酮亮氨酸后，输尿管结扎大鼠的骨骼肌蛋白质含量增加。在每隔5小时喂食亮氨酸的双侧肾切除大鼠中，肝脏糖原和总碳水化合物含量在第20小时至第60小时之间也升高了约10倍。在急性尿毒症大鼠中，单独喂食低蛋白饮食或补充亮氨酸或酮亮氨酸且每隔10小时喂食一次时，骨骼肌糖原之间没有显著差异。亮氨酸通过降低肌肉和肝脏中的磷酸化酶α活性来抑制糖原分解，而酮亮氨酸在急性尿毒症中增强糖原分解。在补充亮氨酸的大鼠中，糖原合成酶I会逐渐失活，这与磷酸化酶α活性的增加同时发生。在每隔5小时喂食亮氨酸补充剂的双侧肾切除大鼠中，肝脏糖原合成酶I的活性增加，最高可达总酶活性的90%。
