Mitch W E, Jurkovitz C, England B K
Renal Division, Emory University School of Medicine, Atlanta, GA 30322.
Am J Kidney Dis. 1993 Jan;21(1):91-5. doi: 10.1016/s0272-6386(12)80729-3.
Anorexia and/or a protein- and calorie-restricted diet can cause protein wasting by limiting the intake of essential amino acids (EAA) and, hence, protein synthesis. By this mechanism plus the effects of inadequate calories, restricted diets could contribute to the loss of lean body mass of uremic patients. Uremia also impairs the normal metabolic responses that must be activated to preserve body protein, thereby augmenting the adverse effects of anorexia. The responses impaired are those that conserve EAA and protein, which results in catabolism of EAA and muscle protein. An important factor that initiates abnormal adaptive responses in uremia is metabolic acidosis, because acidosis stimulates muscle protein degradation and increases the activity of branched-chain ketoacid dehydrogenase and, hence, the catabolism of branched-chain amino acids (BCAA). The effects of acidosis could be mediated by impaired regulation of intracellular pH and/or an increase in glucocorticoid production. Research directed at identifying the specific proteolytic pathways that are activated by metabolic acidosis has excluded a major role for Ca(2+)-activated or lysosomal proteases and suggests activation of an adenosine triphosphate (ATP)- and ubiquitin-dependent proteolytic pathway. The mechanism of activation of this pathway includes an increase in mRNA for enzymes involved in protein and amino acid catabolism.
厌食和/或蛋白质及热量受限饮食会因限制必需氨基酸（EAA）的摄入，进而限制蛋白质合成，导致蛋白质消耗。通过这种机制，再加上热量不足的影响，受限饮食可能会导致尿毒症患者瘦体重的流失。尿毒症还会损害为维持身体蛋白质而必须激活的正常代谢反应，从而加剧厌食的不良影响。受损的反应是那些保存EAA和蛋白质的反应，这会导致EAA和肌肉蛋白的分解代谢。引发尿毒症异常适应性反应的一个重要因素是代谢性酸中毒，因为酸中毒会刺激肌肉蛋白降解，并增加支链酮酸脱氢酶的活性，进而增加支链氨基酸（BCAA）的分解代谢。酸中毒的影响可能是由细胞内pH调节受损和/或糖皮质激素产生增加介导的。旨在确定由代谢性酸中毒激活的特定蛋白水解途径的研究排除了Ca(2+)激活或溶酶体蛋白酶的主要作用，并表明激活了一种三磷酸腺苷（ATP）和泛素依赖性蛋白水解途径。该途径的激活机制包括参与蛋白质和氨基酸分解代谢的酶的mRNA增加。
