Chen Chung-Lin, Fei Zhewei, Carter Edward A, Lu Xiao-Ming, Hu Rey-Heng, Young Vernon R, Tompkins Ronald G, Yu Yong-Ming
Department of Surgery, National Cheng Kung Univversity Hospital, Taiwan, Republic of China.
Metabolism. 2003 Oct;52(10):1232-9. doi: 10.1016/s0026-0495(03)00282-8.
Increased nitrogen loss in the form of urea is a hallmark of the metabolic aberrations that occur after burn injury. As the immediate precursor for urea production is arginine, we have conducted an investigation on the metabolic fate of arginine in the liver to shed light on the metabolic characteristics of this increased nitrogen loss. Livers from 25% total surface burn (n = 8) and sham burn rats (n = 8) were perfused in a recycling fashion with a medium containing amino acids and stable isotope labeled l-[(15) N(2)-guanidino, 5,5-(2)H(2)]arginine for 120 minutes. The rates of glucose and urea production and oxygen consumption were measured. The rate of unidirectional arginine transport and the intrahepatic metabolic fate of arginine in relation to urea cycle activity were quantified by tracing the disappearance rate of the arginine tracer from and the appearance rate of [(15)N(2)]urea in the perfusion medium. Perfused livers from burned rats showed higher rates of total urea production (mean +/- SE, 4.471 +/- 0.274 v 3.235 +/- 0.261 mumol. g dry liver(-1). min(-1); P <.01). This was accompanied by increased hepatic arginine transport (1.269 +/- 0.263 v 0.365 +/- 0.021 mumol. g dry liver(-1). min(-1)) and an increased portion of urea production from the transported extrahepatic arginine (12.9% +/- 2.9% v 3.5% +/- 0.4%, P <.05). The disposal of arginine via nonurea pathways was also increased (0.702 +/- 0.185 v 0.257 +/- 0.025 mumol/g dry weight(-1)/min(-1); P <.05). We propose that increased inward transport and utilization of extrahepatic arginine by the liver contributes to the accelerated urea production after burn injury and accounts, in part, for its conditional essentiality in the nutritional support of burn patients.
以尿素形式增加的氮损失是烧伤后发生的代谢异常的一个标志。由于尿素产生的直接前体是精氨酸，我们对肝脏中精氨酸的代谢命运进行了研究，以阐明这种增加的氮损失的代谢特征。将25%体表烧伤大鼠（n = 8）和假烧伤大鼠（n = 8）的肝脏以循环方式用含有氨基酸和稳定同位素标记的l-[(15)N(2)-胍基，5,5-(2)H(2)]精氨酸的培养基灌注120分钟。测量葡萄糖和尿素的产生速率以及耗氧率。通过追踪灌注培养基中精氨酸示踪剂的消失速率和[(15)N(2)]尿素的出现速率，对单向精氨酸转运速率以及精氨酸在肝脏内与尿素循环活性相关的代谢命运进行定量。烧伤大鼠的灌注肝脏显示出更高的总尿素产生速率（平均值±标准误，4.471±0.274对3.235±0.261 μmol·g干肝(-1)·min(-1)；P <.01）。这伴随着肝脏精氨酸转运增加（1.269±0.263对0.365±0.021 μmol·g干肝(-1)·min(-1)）以及从转运的肝外精氨酸产生的尿素部分增加（12.9%±2.9%对3.5%±0.4%，P <.05）。通过非尿素途径处理精氨酸也增加了（0.702±0.185对0.257±0.025 μmol/g干重(-1)/min(-1)；P <.05）。我们提出，肝脏对肝外精氨酸的内向转运和利用增加导致烧伤后尿素产生加速，并且部分解释了其在烧伤患者营养支持中的条件必需性。
