Yoshida S, Ishibashi N, Noake T, Shirouzu Y, Oka T, Shirouzu K
First Department of Surgery, School of Medicine, Kurume University, Fukuoka, Japan.
Metabolism. 1997 Apr;46(4):370-3. doi: 10.1016/s0026-0495(97)90049-4.
Arginine supplementation increases glutamine levels in muscle and plasma. Since glutamine production is increased in catabolic states, these observations prompted us to investigate whether the flux of arginine to glutamine was increased in tumor-bearing (TB) rats, and we measured the synthesis rate of glutamine from arginine in control versus TB rats receiving standard total parenteral nutrition (TPN) solution. Male Donryu rats (N = 36; body weight, 200 to 225 g) were divided into two groups, control and TB rats. Yoshida sarcoma cells (1 x 10(6)) were inoculated into the back of the rats (n = 18) subcutaneously on day 0. The rats were given free access to water and rat chow. On day 5, all animals, including non-TB rats (n = 18), were catheterized at the jugular vein and TPN was begun. On day 10, TPN solution containing either U-14C-glutamine (2.0 microCi/h) or U-14C-arginine (2.0 microCi/h) was infused as a 6-hour constant infusion. At the end of the isotope infusion, plasma was collected to determine the glutamine production rate in rats receiving U-14C-glutamine, and the ratio of specific activity of glutamine to specific activity of arginine was measured in rats receiving U-14C-arginine. Only 2 g tumor caused a decrease in glutamine levels and an increase in glutamine and arginine production. The low flux rate of arginine to glutamine was observed in control rats (Arg to Gln, 41.0 +/- 11.9 mumol/kg/h). On the other hand, TB caused a significant increase in Arg to Gln compared with the control (213.3 +/- 66.1 mumol/kg/h, P < .01 v control). An increase in the flux rate of Arg to Gln was associated with an enhancement in the ratio of specific activity of ornithine to specific activity of arginine in TB rats (control 51.5% +/- 10.9% v 77.4% +/- 8.9%, P < .05). We conclude that (1) glutamine and arginine metabolism is altered with very small tumors, (2) although the flux of Arg to Gln was increased in TB and rats, the small increase in Arg to Gln cannot explain the observed large increase in Gln production.
补充精氨酸可提高肌肉和血浆中的谷氨酰胺水平。由于分解代谢状态下谷氨酰胺的生成会增加，这些观察结果促使我们研究荷瘤（TB）大鼠中精氨酸向谷氨酰胺的通量是否增加，我们测量了接受标准全胃肠外营养（TPN）溶液的对照大鼠与荷瘤大鼠中精氨酸合成谷氨酰胺的速率。将雄性Donryu大鼠（N = 36；体重200至225克）分为两组，即对照大鼠和荷瘤大鼠。在第0天，将吉田肉瘤细胞（1×10⁶）皮下接种到大鼠（n = 18）的背部。大鼠可自由饮水和进食大鼠饲料。在第5天，对所有动物，包括非荷瘤大鼠（n = 18），进行颈静脉插管并开始给予TPN。在第10天，以6小时持续输注的方式输注含有U-¹⁴C-谷氨酰胺（2.0微居里/小时）或U-¹⁴C-精氨酸（2.0微居里/小时）的TPN溶液。在同位素输注结束时，收集血浆以测定接受U-¹⁴C-谷氨酰胺的大鼠中谷氨酰胺的生成速率，并测定接受U-¹⁴C-精氨酸的大鼠中谷氨酰胺比活性与精氨酸比活性的比值。仅2克肿瘤就导致谷氨酰胺水平降低以及谷氨酰胺和精氨酸生成增加。在对照大鼠中观察到精氨酸向谷氨酰胺的通量率较低（精氨酸向谷氨酰胺，41.0±11.9微摩尔/千克/小时）。另一方面，与对照相比，荷瘤导致精氨酸向谷氨酰胺的通量显著增加（213.3±66.1微摩尔/千克/小时，与对照相比P <.01）。在荷瘤大鼠中，精氨酸向谷氨酰胺的通量率增加与鸟氨酸比活性与精氨酸比活性的比值升高相关（对照为51.5%±10.9%，而荷瘤大鼠为77.4%±8.9%，P <.05）。我们得出结论：（1）谷氨酰胺和精氨酸代谢在肿瘤非常小的时候就会发生改变；（2）尽管荷瘤大鼠中精氨酸向谷氨酰胺的通量增加，但精氨酸向谷氨酰胺的小幅增加无法解释所观察到的谷氨酰胺生成的大幅增加。
