Espat N J, Bode B P, Lind D S, Copeland E M, Souba W W
Department of Surgery, University of Florida College of Medicine, Gainesville.
Ann Surg. 1995 Jan;221(1):50-8. doi: 10.1097/00000658-199501000-00006.
The liver of the host with cancer requires increased amounts of amino acids to support the synthesis of glucose and key defense proteins. To study the effect of the growing tumor on hepatic amino acid uptake, the authors measured hepatic transport activity in tumor-bearing rats and in rats at various times after tumor resection.
Fischer-344 rats were implanted subcutaneously with methylcholanthrene-induced fibrosarcoma cells (MCA sarcoma). When the tumors reached 10% of body weight, hepatic amino acid transport activity was assayed or the animals underwent surgical removal of the tumor. In animals that underwent tumor excision, livers were removed at 1, 3, or 5 days post-resection, and hepatic plasma membrane vesicles (HPMVs) were prepared. Nontumor-bearing pair-fed rats undergoing sham implantation or sham resection served as controls. System N (glutamine), System A (MeAIB), and System y+ (arginine) transport activity were assayed, which allowed the authors to compare differences in tumor-induced rates of transport and the influence of resection on transport activity.
System A transport activity was unaltered by tumor growth. In contrast, the presence of the growing tumor increased arginine and glutamine uptake by the liver. Hepatic glutamine transport remained elevated for 5 days after tumor resection, although by postoperative day 5 there was a trend toward normalization. In contrast, arginine transport remained increased by twofold onpost-resection day 1 and had normalized by postoperative day 3. The enhanced arginine transport was a result of an increase in maximal transport velocity (Vmax) rather than a change in carrier affinity.
Increases in hepatic amino acid transport normalize within several days of tumor resection, indicating a key role for the tumor in the induction of this response. The observation that hepatic glutamine transport activity remains augmented after tumor resection longer than any other transporter studied suggests a key role for this amino acid in overall hepatic nitrogen metabolism and may partially explain the persistent glutamine depletion that is characteristic of the tumor-bearing host.
患癌宿主的肝脏需要更多的氨基酸来支持葡萄糖和关键防御蛋白的合成。为了研究生长中的肿瘤对肝脏氨基酸摄取的影响，作者测量了荷瘤大鼠以及肿瘤切除后不同时间点大鼠的肝脏转运活性。
将甲基胆蒽诱导的纤维肉瘤细胞（MCA肉瘤）皮下植入Fischer-344大鼠体内。当肿瘤达到体重的10%时，测定肝脏氨基酸转运活性，或者对动物进行肿瘤手术切除。在接受肿瘤切除的动物中，于切除后1、3或5天取出肝脏，并制备肝细胞膜囊泡（HPMV）。接受假植入或假切除的非荷瘤配对喂养大鼠作为对照。测定系统N（谷氨酰胺）、系统A（甲基氨基异丁酸）和系统y+（精氨酸）的转运活性，这使作者能够比较肿瘤诱导的转运速率差异以及切除对转运活性的影响。
系统A的转运活性不受肿瘤生长的影响。相比之下，生长中的肿瘤的存在增加了肝脏对精氨酸和谷氨酰胺的摄取。肿瘤切除后，肝脏谷氨酰胺转运在5天内一直升高，尽管到术后第5天有恢复正常的趋势。相比之下，精氨酸转运在切除后第1天增加了两倍，并在术后第3天恢复正常。精氨酸转运增强是最大转运速度（Vmax）增加的结果，而不是载体亲和力的改变。
肝脏氨基酸转运在肿瘤切除后数天内恢复正常，表明肿瘤在诱导这种反应中起关键作用。肝脏谷氨酰胺转运活性在肿瘤切除后比所研究的任何其他转运体持续增强的时间更长，这一观察结果表明该氨基酸在肝脏整体氮代谢中起关键作用，并且可能部分解释了荷瘤宿主持续的谷氨酰胺消耗这一特征。
