Holeček Milan
Department of Physiology, Faculty of Medicine, Charles University, 500 03 Hradec Kralove, Czech Republic.
Metabolites. 2022 Oct 13;12(10):971. doi: 10.3390/metabo12100971.
Studies from the last decades indicate that increased levels of ammonia contribute to muscle wasting in critically ill patients. The aim of the article is to examine the effects of two different causes of hyperammonemia-increased ATP degradation in muscles during strenuous exercise and impaired ammonia detoxification to urea due to liver cirrhosis. During exercise, glycolysis, citric acid cycle (CAC) activity, and ATP synthesis in muscles increase. In cirrhosis, due to insulin resistance and mitochondrial dysfunction, glycolysis, CAC activity, and ATP synthesis in muscles are impaired. Both during exercise and in liver cirrhosis, there is increased ammonia detoxification to glutamine (Glu + NH + ATP → Gln + ADP + Pi), increased drain of ketoglutarate (α-KG) from CAC for glutamate synthesis by α-KG-linked aminotransferases, glutamate, aspartate, and α-KG deficiency, increased oxidation of branched-chain amino acids (BCAA; valine, leucine, and isoleucine), and protein-energy wasting in muscles. It is concluded that ammonia can contribute to muscle wasting regardless of the cause of its increased levels and that similar strategies can be designed to increase muscle performance in athletes and reduce muscle loss in patients with hyperammonemia. The pros and cons of glutamate, α-KG, aspartate, BCAA, and branched-chain keto acid supplementation are discussed.
过去几十年的研究表明，氨水平升高会导致重症患者肌肉萎缩。本文旨在研究高氨血症的两种不同病因的影响——剧烈运动期间肌肉中ATP降解增加以及肝硬化导致氨向尿素的解毒受损。运动期间，肌肉中的糖酵解、柠檬酸循环（CAC）活性和ATP合成增加。在肝硬化中，由于胰岛素抵抗和线粒体功能障碍，肌肉中的糖酵解、CAC活性和ATP合成受损。在运动和肝硬化期间，氨向谷氨酰胺的解毒均增加（谷氨酸+氨+ATP→谷氨酰胺+ADP+磷酸），通过α-酮戊二酸连接的转氨酶从CAC中排出用于谷氨酸合成的α-酮戊二酸增加，谷氨酸、天冬氨酸和α-酮戊二酸缺乏，支链氨基酸（BCAA；缬氨酸、亮氨酸和异亮氨酸）氧化增加，以及肌肉中的蛋白质能量消耗。得出的结论是，无论氨水平升高的原因如何，氨都可能导致肌肉萎缩，并且可以设计类似的策略来提高运动员的肌肉性能和减少高氨血症患者的肌肉损失。文中讨论了补充谷氨酸、α-酮戊二酸、天冬氨酸、BCAA和支链酮酸的利弊。
