Glutamine metabolism in the kidney during induction of, and recovery from, metabolic acidosis in the rat.
Glutamine metabolism in the kidney during induction of, and recovery from, metabolic acidosis in the rat.
复制标题
在大鼠代谢性酸中毒的诱导和恢复过程中，肾脏中的谷氨酰胺代谢。
作者：
David M. Parry;J. Brosnan
在大鼠上进行实验以评估肾转氨酶活性、线粒体对谷氨酰胺的通透性、磷酸烯醇式丙酮酸羧激酶活性和全身酸碱变化在控制肾氨（NH（3）+NH（4）（+））产生中的可能调节作用。通过自由饮用氯化铵溶液诱导酸中毒。无呼吸代偿的明显代谢性酸中毒[pH=7.25; HCO（3）（-）= 16.9毫当量/升; pCO（2）=40.7mmHg（5.41kPa）]，但此后酸碱状态恢复正常。这种酸碱状态的改善伴随着约2天后达到最大氨排泄率（开始阶段）。然后维持稳定的氨排泄速率（平台期），直到大鼠用自来水代替NH（4）Cl溶液，此时pCO（2）和HCO（3）（-）升高[55.4mmHg（7.37kPa）和35.5mequiv./min]。L]，肾氨排泄在1天内恢复至对照值（恢复期）。谷氨酰胺的肾动静脉差异总是高于氨排泄率。磷酸依赖性转氨酶和磷酸烯醇式丙酮酸羧激酶活性以及离体肾脏线粒体的谷氨酰胺代谢速率（NH3产生和O2消耗）在发病期均升高。转氨酶和线粒体代谢的增加持续到平台期，而羧激酶的增加与氨排泄同时达到平台期。在恢复阶段，羧激酶活性的快速下降伴随着氨排泄的减少，而谷氨酰胺酶和线粒体谷氨酰胺代谢在体外仍然升高。恢复期间，肾皮质切片的谷氨酰胺代谢（氨、谷氨酸和葡萄糖生成）与体内谷氨酰胺代谢一致，即恢复至对照值。结果表明，线粒体谷氨酰胺代谢的适应必须由线粒体外因素调节，因为谷氨酰胺在体内和切片中的代谢在恢复期间返回到控制值，而谷氨酰胺的线粒体代谢保持升高。
Experiments were carried out on rats to evaluate the possible regulatory roles of renal glutaminase activity, mitochondrial permeability to glutamine, phosphoenolpyruvate carboxykinase activity and systemic acid-base changes in the control of renal ammonia (NH(3) plus NH(4) (+)) production. Acidosis was induced by drinking NH(4)Cl solution ad libitum. A pronounced metabolic acidosis without respiratory compensation [pH=7.25; HCO(3) (-)=16.9mequiv./litre; pCO(2)=40.7mmHg (5.41kPa)] was evident for the first 2 days, but thereafter acid-base status returned towards normal. This improvement in acid-base status was accompanied by the attainment of maximal rates of ammonia excretion (onset phase) after about 2 days. A steady rate of ammonia excretion was then maintained (plateau phase) until the rats were supplied with tap water in place of the NH(4)Cl solution, whereupon pCO(2) and HCO(3) (-) became elevated [55.4mmHg (7.37kPa) and 35.5mequiv./litre] and renal ammonia excretion returned to control values within 1 day (recovery phase). Renal arteriovenous differences for glutamine always paralleled rates of ammonia excretion. Phosphate-dependent glutaminase and phosphoenolpyruvate carboxykinase activities and the rate of glutamine metabolism (NH(3) production and O(2) consumption) by isolated kidney mitochondria all increased during the onset phase. The increases in glutaminase and in mitochondrial metabolism continued into the plateau phase, whereas the increase in the carboxykinase reached a plateau at the same time as did ammonia excretion. During the recovery phase a rapid decrease in carboxykinase activity accompanied the decrease in ammonia excretion, whereas glutaminase and mitochondrial glutamine metabolism in vitro remained elevated. The metabolism of glutamine by kidney-cortex slices (ammonia, glutamate and glucose production) paralleled the metabolism of glutamine in vivo during recovery, i.e. it returned to control values. The results indicate that the adaptations in mitochondrial glutamine metabolism must be regulated by extra-mitochondrial factors, since glutamine metabolism in vivo and in slices returns to control values during recovery, whereas the mitochondrial metabolism of glutamine remains elevated.