Holecek Milan, Rysava Radana, Safranek Roman, Kadlcikova Jana, Sprongl Ludek
Department of Physiology, Charles Unviersity Prague, Medical Faculty, Hradec Kralove, Czech Republic.
Metabolism. 2003 Aug;52(8):1062-7. doi: 10.1016/s0026-0495(03)00107-0.
Glutamine deficiency, a common finding in severe illness, has a negative influence on immune status, protein metabolism, and disease outcome. In several studies, a close relationship between glutamine, branched-chain amino acid (BCAA), and protein metabolism was demonstrated. The aim of the present study was to investigate the effect of glutamine deficiency on amino acid and protein metabolism in hepatic tissue using a model of isolated perfused rat liver (IPRL). Parameters of protein metabolism and amino acid metabolism were measured using both recirculation and single pass technique with L-[1-(14)C]leucine and [1-(14)C]ketoisocaproate (KIC) as a tracer. Glutamine concentration in perfusion solution was 0.5 mmol/L in control and 0 mmol/L in the glutamine-deficient group. The net release of glutamine (about 11 micromol/g/h) and higher net uptake of most of the amino acids was observed in the glutamine-deficient group. There was an insignificant effect of lack of glutamine on hepatic protein synthesis, proteolysis, and the release of urea. However, significantly lower release of proteins by the liver perfused with glutamine-deficient solution was observed. The lack of glutamine in perfusion solution caused a significant decrease in leucine oxidation (6.66 +/- 1.04 v 13.67 +/- 2.38, micromol/g dry liver/h, P <.05) and an increase in KIC oxidation (163.7 +/- 16.5 v 92.0 +/- 12.9 micromL/g dry liver/h, P <.05). We conclude that decreased delivery of glutamine to hepatic tissue activates glutamine synthesis, decreases resynthesis of essential BCAA from branched-chain keto acids (BCKA), increases catabolism of BCKA, and has an insignificant effect on protein turnover in hepatic tissue.
谷氨酰胺缺乏是重症患者的常见现象，对免疫状态、蛋白质代谢和疾病转归有负面影响。多项研究表明，谷氨酰胺、支链氨基酸（BCAA）与蛋白质代谢之间存在密切关系。本研究旨在利用离体灌注大鼠肝脏（IPRL）模型，探讨谷氨酰胺缺乏对肝组织氨基酸和蛋白质代谢的影响。采用再循环和单程技术，以L-[1-(14)C]亮氨酸和[1-(14)C]酮异己酸（KIC）作为示踪剂，测定蛋白质代谢和氨基酸代谢参数。对照组灌注液中谷氨酰胺浓度为0.5 mmol/L，谷氨酰胺缺乏组为0 mmol/L。在谷氨酰胺缺乏组中，观察到谷氨酰胺的净释放（约11 μmol/g/h）以及大多数氨基酸的净摄取增加。谷氨酰胺缺乏对肝脏蛋白质合成、蛋白水解和尿素释放的影响不显著。然而，观察到用谷氨酰胺缺乏溶液灌注的肝脏蛋白质释放明显降低。灌注液中缺乏谷氨酰胺导致亮氨酸氧化显著减少（6.66±1.04对13.67±2.38，μmol/g干肝/h，P<.05），KIC氧化增加（163.7±16.5对92.0±12.9 μmol/g干肝/h，P<.05）。我们得出结论，向肝组织输送的谷氨酰胺减少会激活谷氨酰胺合成，减少支链酮酸（BCKA）重新合成必需BCAA，增加BCKA的分解代谢，对肝组织中的蛋白质周转影响不显著。
