May R C, Masud T, Logue B, Bailey J, England B K
Renal Division, Emory University School of Medicine, Atlanta, Ga.
Miner Electrolyte Metab. 1992;18(2-5):245-9.
Previous work documented an acceleration of proteolysis and branched-chain amino acid oxidation when muscles from rats with chronic metabolic acidosis were incubated in vitro. The present study examines the impact of chronic metabolic acidosis on whole body amino acid turnover and oxidation in chronically catheterized, awake, male Sprague-Dawley rats using stochastic modeling and a primed continuous infusion of L[1-14C] leucine. Whole body protein turnover was accelerated by acidosis as reflected in a 70% increase in proteolysis and a 55% increase in protein synthesis. Amino acid oxidation was increased by 145% in rats with acidosis relative to control rats receiving diets identical in protein and calories based on a reciprocal pool model and plasma alpha-ketoisocaproate specific radioactivity. These changes were accompanied by a 104% increase in liver branched-chain ketoacid dehydrogenase (BCKAD) activity in rats with acidosis, similar to previously documented increases in skeletal muscle BCKAD activity caused by acidosis. In contrast, kidney BCKAD activity was decreased by 38%, illustrating the tissue specificity of the changes that were present. We conclude that chronic metabolic acidosis accelerates whole body protein turnover and reduces the efficiency of protein utilization by accelerating amino acid oxidation. These changes may require an intact glucocorticoid axis.
先前的研究记录了慢性代谢性酸中毒大鼠的肌肉在体外孵育时蛋白水解和支链氨基酸氧化加速的现象。本研究使用随机模型和L-[1-14C]亮氨酸的预充连续输注，考察慢性代谢性酸中毒对长期插管、清醒的雄性Sprague-Dawley大鼠全身氨基酸周转和氧化的影响。酸中毒加速了全身蛋白质周转，蛋白水解增加70%，蛋白质合成增加55%。根据互逆池模型和血浆α-酮异己酸比放射性，酸中毒大鼠的氨基酸氧化相对于接受相同蛋白质和热量饮食的对照大鼠增加了145%。这些变化伴随着酸中毒大鼠肝脏支链酮酸脱氢酶（BCKAD）活性增加104%，这与先前记录的酸中毒引起的骨骼肌BCKAD活性增加相似。相比之下，肾脏BCKAD活性降低了38%，说明存在组织特异性变化。我们得出结论，慢性代谢性酸中毒通过加速氨基酸氧化来加速全身蛋白质周转并降低蛋白质利用效率。这些变化可能需要完整的糖皮质激素轴。
