Welbourne T C
Department of Physiology, Louisiana State University Medical Center, Shreveport.
Am J Kidney Dis. 1989 Oct;14(4):293-7. doi: 10.1016/s0272-6386(89)80206-9.
The amino acid glutamine serves as a major fuel, powering tubular transport processes and base generation in the kidneys of acidotic animals. Removing the adrenals limits the kidneys' response to an exogenous acid load and impairs the removal rate of glutamine from the blood. Administering glucocorticoid to adrenalectomized (ADX) rats reverses a small net release of glutamine to uptake; similarly, administering an exogenous acid load to ADX rats restores the kidneys to organs of net extraction. Glucocorticoid-induced uptake is substantially less than the filtered glutamine load in contrast to uptake across both the luminal and basolateral surfaces when filtered HCO3- is reduced. Furthermore, mitochondrial glutamine oxidation is glucocorticoid dependent with a distinct impairment exhibited by the ADX acidotic rat kidney. However, combining the effect of reduced filtered HCO3- with glucocorticoid supplementation results in a marked potentiation of glutamine uptake coupled to oxidation. These results are consistent with a proposed proximal tubule cell model in which basolateral glutamine uptake is inversely related to basolateral HCO3- efflux and coupled, in the presence of glucocorticoid, to mitochondrial oxidation. This model of glucocorticoid-induced ammoniagenesis predicts an increased renal work capacity when basolateral transport of a major metabolic fuel, glutamine, is closely coupled to its oxidative metabolism.
氨基酸谷氨酰胺作为一种主要燃料，为酸中毒动物肾脏中的肾小管转运过程和碱基生成提供能量。摘除肾上腺会限制肾脏对外源性酸负荷的反应，并损害谷氨酰胺从血液中的清除率。给肾上腺切除（ADX）大鼠注射糖皮质激素可使谷氨酰胺的小量净释放转变为摄取；同样，给ADX大鼠施加外源性酸负荷可使肾脏恢复为净摄取器官。与滤过的HCO3-减少时管腔和基底外侧表面的摄取相比，糖皮质激素诱导的摄取显著低于滤过的谷氨酰胺负荷。此外，线粒体谷氨酰胺氧化依赖于糖皮质激素，ADX酸中毒大鼠肾脏表现出明显的损伤。然而，将滤过的HCO3-减少的效应与补充糖皮质激素相结合，会导致谷氨酰胺摄取与氧化的显著增强。这些结果与提出的近端小管细胞模型一致，在该模型中，基底外侧谷氨酰胺摄取与基底外侧HCO3-流出呈负相关，并在糖皮质激素存在的情况下与线粒体氧化偶联。这种糖皮质激素诱导氨生成的模型预测，当主要代谢燃料谷氨酰胺的基底外侧转运与其氧化代谢紧密偶联时，肾脏工作能力会增加。
