Inhibition of muscle glutamine formation in hypercatabolic patients
Inhibition of muscle glutamine formation in hypercatabolic patients
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DOI：
10.1042/cs19990254
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发表时间：
2000-09-01
期刊：
影响因子：
6
通讯作者：
Wolfe, RR
中科院分区：
文献类型：
--
作者：
Biolo, G;Fleming, RYD;Wolfe, RR
谷氨酰胺主要在骨骼肌中合成，并使氮转移到肝脏，以及提供其他功能。越来越多的证据表明，谷氨酰胺补充剂对危重患者有有益的临床效果。然而，对内源性谷氨酰胺形成对严重胁迫的响应知之甚少。本文测定了20例严重烧伤病人和19例正常人小腿骨骼肌吸收后的净蛋白平衡率、亮氨酸氧化脱羧率、丙氨酸和谷氨酰胺合成率。患者在烧伤后14 +/-5天进行研究，其平均烧伤面积为总体表面积的66 +/-18%。方法以下肢动静脉平衡技术结合股外侧肌活检为基础。在吸收后状态下，与健康对照受试者相比，严重烧伤患者表现出加速的肌肉损失（+150%）（即蛋白水解减去合成）和亮氨酸氧化脱羧（+117%），以及肌内游离谷氨酰胺池的消耗（-63%）。烧伤患者骨骼肌谷氨酰胺从头合成的平均速率降低了48%，而丙氨酸从头净合成的平均速率增加了174%。总之，在严重的高分解代谢烧伤患者，肌肉谷氨酰胺的形成受到抑制，而丙氨酸是器官间氮运输的主要载体。这些变化解释了在长期严重应激期间谷氨酰胺可用性的降低。
Glutamine is synthesized primarily in skeletal muscle, and enables transfer of nitrogen to the liver, as well as serving other functions. There is increasing evidence for beneficial clinical effects of glutamine supplementation in critically ill patients. However, the response of endogenous glutamine formation to severe stress is poorly understood. The rates of net protein balance, leucine oxidative decarboxylation, and alanine and glutamine synthesis de novo were determined in leg skeletal muscle of 20 severely burned patients and 19 normal controls in the post-absorptive state. Patients were studied at 14 +/- 5 days post-burn, and their mean burn size was 66 +/- 18% of total body surface area. Methods were based on the leg arteriovenous balance technique in combination with biopsies of the vastus lateralis muscle. In the post-absorptive state, patients with severe burns, as compared with healthy control subjects, exhibited accelerated muscle loss (+ 150%) (i.e. proteolysis minus synthesis) and leucine oxidative decarboxylation (+ 117%), and depletion of the intramuscular free glutamine pool (- 63%). The average rate of glutamine synthesis de novo was decreased by 48%, whereas net alanine synthesis de novo was increased by 174%, in skeletal muscle of burned patients. In conclusion, in severely hypercatabolic burned patients, muscle glutamine formation was suppressed, whereas alanine was the major vehicle for inter-organ nitrogen transport. These changes account for a decreased glutamine availability during prolonged severe stress.