Pacitti A J, Chen M K, Bland K I, Copeland E M, Souba W W
Department of Surgery, University of Florida, Gainesville 32610.
Surg Oncol. 1992 Apr;1(2):173-82. doi: 10.1016/0960-7404(92)90031-f.
The mechanisms potentially controlling the net release of glutamine by the liver that occurs in tumour-bearing rats were investigated. Studies were undertaken when the tumour comprised approximately 7% (15 +/- 2 g) of total body weight. Hepatic glutamine gradient ratios were calculated by dividing hepatic glutamine content by arterial blood glutamine concentration. Both sodium-dependent and sodium-independent hepatocyte carrier-mediated glutamine transport were evaluated employing hepatic plasma membrane vesicles (HPMVs). In TBR the hepatic glutamine gradient ratio doubled (P < 0.001) secondary to a 52% increase in hepatic content (P < 0.005) and a 16% decrease in circulating glutamine (P < 0.001). Sodium-dependent glutamine transport was increased in HPMVs from TBR secondary to a 24 +/- 4% increase in the maximal velocity of transport (Vmax; P < 0.01) without alteration in apparent transporter affinity (Km). Saturable sodium-independent carrier-mediated glutamine transport was increased in HPMVs from TBR over CONT to a much greater relative degree owing to a 2.7-fold increase in transport Vmax (P < 0.05) without a change in transport Km. The accelerated hepatic efflux of glutamine which characterizes malignant growth appears to be the result of both mass-action gradient phenomena and alterations at the level of hepatocyte membrane transport activity.
研究了荷瘤大鼠肝脏中潜在控制谷氨酰胺净释放的机制。当肿瘤约占总体重的7%（15±2克）时进行了相关研究。肝谷氨酰胺梯度比通过肝谷氨酰胺含量除以动脉血谷氨酰胺浓度来计算。采用肝细胞膜囊泡（HPMV）评估了钠依赖性和非钠依赖性肝细胞载体介导的谷氨酰胺转运。在荷瘤大鼠中，肝谷氨酰胺梯度比翻倍（P<0.001），这是由于肝脏含量增加52%（P<0.005）和循环谷氨酰胺减少16%（P<0.001）所致。荷瘤大鼠的HPMV中钠依赖性谷氨酰胺转运增加，这是由于转运最大速度（Vmax）增加24±4%（P<0.01），而转运体表观亲和力（Km）未改变。与对照组相比，荷瘤大鼠的HPMV中可饱和的非钠依赖性载体介导的谷氨酰胺转运增加到更大的相对程度，这是由于转运Vmax增加2.7倍（P<0.05），而转运Km没有变化。以恶性生长为特征的谷氨酰胺肝外流加速似乎是质量作用梯度现象和肝细胞膜转运活性水平改变的结果。
