The effect of metabolic acidosis on the synthesis and turnover of rat renal phosphate-dependent glutaminase.
The effect of metabolic acidosis on the synthesis and turnover of rat renal phosphate-dependent glutaminase.
复制标题
代谢性酸中毒对大鼠肾磷酸盐依赖性谷氨酰胺酶合成和周转的影响。
作者：
J. Tong;G. Harrison;N. Curthoys
线粒体磷酸盐依赖性转氨酶活性的调节是控制肾氨生成的重要组成部分。酸碱平衡的改变显著影响大鼠肾脏中存在的转氨酶的量，但不影响大脑或小肠中的转氨酶的量。通过比较掺入特异性免疫沉淀物中的[35S]甲硫氨酸与掺入总蛋白中的甲硫氨酸的量，确定转氨酶合成的相对速率。在正常动物中，转氨酶的合成率占总蛋白质合成的0.04%。代谢性酸中毒7天后，肾转氨酶活性增加至正常值的5倍。在酸中毒发作期间，合成的相对速率增加比转氨酶活性增加的外观更快。增加的合成速率在5天内达到一个平台，其值是正常值的5.3倍。慢性酸中毒恢复后，转氨酶合成的相对速率迅速下降，但转氨酶活性逐渐降低。前者在2天内恢复正常，而后者需要11天。正常和酸中毒大鼠的转氨酶降解的表观半衰期分别为5.1天和4.7天。这些结果表明，与代谢性酸中毒相关的肾转氨酶活性增加主要是由于其合成速率增加。从酸中毒恢复后发生的活性降低来看，谷氨酰胺酶的真实半衰期估计为3天。
Regulation of the mitochondrial phosphate-dependent glutaminase activity is an essential component in the control of renal ammoniagenesis. Alterations in acid-base balance significantly affect the amount of the glutaminase that is present in rat kidney, but not in brain or small intestine. The relative rates of glutaminase synthesis were determined by comparing the amount of [35S]methionine incorporated into specific immunoprecipitates with that incorporated into total protein. In a normal animal, the rate of glutaminase synthesis constitutes 0.04% of the total protein synthesis. After 7 days of metabolic acidosis, the renal glutaminase activity is increased to a value that is 5-fold greater than normal. During onset of acidosis, the relative rate of synthesis increases more rapidly than the appearance of increased glutaminase activity. The increased rate of synthesis reaches a plateau within 5 days at a value that is 5.3-fold greater than normal. Recovery from chronic acidosis causes a rapid decrease in the relative rate of glutaminase synthesis, but a gradual decrease in glutaminase activity. The former returns to normal within 2 days, whereas the latter requires 11 days. The apparent half-time for glutaminase degradation was found to be 5.1 days and 4.7 days for normal and acidotic rats respectively. These results indicate that the increase in renal glutaminase activity associated with metabolic acidosis is due primarily to an increase in its rate of synthesis. From the decrease in activity that occurs upon recovery from acidosis, the true half-life for the glutaminase was estimated to be 3 days.