Almond M K, Smith A, Cohen R D, Iles R A, Flynn G
Medical Unit, London Hospital Medical College, University of London, U.K.
Biochem J. 1991 Sep 15;278 ( Pt 3)(Pt 3):709-14. doi: 10.1042/bj2780709.
Switching in acidosis of hepatic nitrogen disposal from urea synthesis to NH4+ and net glutamine production was demonstrated in the isolated perfused livers of starved male Wistar rats. Lactate was preferred to glucose as the substrate for the carbon skeleton of glutamine synthesized over the pH range 6.9-7.5. This is necessary if the switch away from a proton-producing process (ureagenesis) in acidosis is to constitute an acid-base regulating system intrinsic to the liver. Glutamine balance shifted with pH from marked net uptake to small net output under acidotic conditions (pH 7.5-6.9), an effect due solely to a decrease in glutamine uptake. NH4+ uptake by the liver had a linear relationship with pH, being markedly decreased in acidosis because glutamine synthesis was insufficient to compensate for the decreased incorporation into urea. Animals rendered chronically acidotic showed a lower central venous plasma urea concentration and a raised NH4+ concentration, but their livers synthesized no more glutamine when perfused at an acidotic pH than did normal livers. We conclude that perivenous hepatocytes may not be efficient scavengers of NH4+ ions, which must be partly disposed of elsewhere by non-proton-generating pathways if inhibition of ureagenesis is to represent a hepatic acid-base regulating system.
在饥饿雄性Wistar大鼠的离体灌注肝脏中，已证实肝脏氮代谢在酸中毒时从尿素合成转变为生成NH₄⁺并净生成谷氨酰胺。在pH值6.9 - 7.5范围内，乳酸比葡萄糖更适合作为合成谷氨酰胺碳骨架的底物。如果在酸中毒时从产生质子的过程（尿素生成）转变要构成肝脏固有的酸碱调节系统，这是必要的。在酸中毒条件下（pH 7.5 - 6.9），谷氨酰胺平衡随pH值从显著的净摄取转变为少量的净输出，这种效应完全是由于谷氨酰胺摄取减少所致。肝脏对NH₄⁺的摄取与pH值呈线性关系，在酸中毒时显著降低，因为谷氨酰胺合成不足以补偿尿素合成中NH₄⁺掺入量的减少。长期处于酸中毒状态的动物，其中心静脉血浆尿素浓度较低，NH₄⁺浓度升高，但在酸中毒pH值下灌注时，其肝脏合成的谷氨酰胺并不比正常肝脏多。我们得出结论，肝小叶周边的肝细胞可能不是NH₄⁺离子的有效清除者，如果抑制尿素生成要代表一种肝脏酸碱调节系统，那么NH₄⁺离子必须部分通过不产生质子的途径在其他地方进行处理。
