Almond M K, Iles R A, Cohen R D
Medical Unit, London Hospital Medical College, UK.
Miner Electrolyte Metab. 1992;18(2-5):237-40.
Switching of hepatic nitrogen disposal from urea synthesis to glutamine production has been proposed as a mechanism for countering acidosis, with glutamine synthesis providing a route for the detoxification of ammonium not incorporated into urea. Isolated livers from starved rats were perfused with ammonium (0.8 mM); increasing perfusate lactate concentration 0-2 mM raised glutamine synthesis threefold whilst increasing perfusate glucose concentration 0-20 mM did not. This was true under normal and acidotic conditions. In the presence of both substrates plus either 14C-glucose or 14C-lactate, the mean specific activity of glutamine synthesised was greater for 14C-lactate. Thus, the preferred substrate for hepatic glutamine synthesis is lactate, a proton neutral reaction. Perfusion with lactate and glutamine over the pH range 6.9-7.5 with or without the glutamine synthase inhibitor L-methionine-s-sulphoxime showed that the switch in acidosis to net glutamine production is entirely due to inhibition of glutamine removal by periportal hepatocytes.
肝脏氮处置从尿素合成转向谷氨酰胺生成已被提出作为对抗酸中毒的一种机制，谷氨酰胺合成提供了一条未掺入尿素的铵解毒途径。用铵（0.8 mM）灌注饥饿大鼠的离体肝脏；将灌注液乳酸浓度从0增加到2 mM可使谷氨酰胺合成增加三倍，而将灌注液葡萄糖浓度从0增加到20 mM则不会。在正常和酸中毒条件下均如此。在两种底物同时存在且添加14C-葡萄糖或14C-乳酸的情况下，合成的谷氨酰胺的平均比活性对于14C-乳酸更高。因此，肝脏谷氨酰胺合成的首选底物是乳酸，这是一个质子中性反应。在pH范围6.9 - 7.5下用乳酸和谷氨酰胺灌注，无论有无谷氨酰胺合成酶抑制剂L-蛋氨酸-s-亚砜肟，结果表明酸中毒时转向净谷氨酰胺生成完全是由于门静脉周围肝细胞对谷氨酰胺清除的抑制。
