Bidirectional substrate fluxes through the System N (SNAT5) glutamine transporter may determine net glutamine flux in rat liver
Bidirectional substrate fluxes through the System N (SNAT5) glutamine transporter may determine net glutamine flux in rat liver
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DOI：
10.1113/jphysiol.2003.060293
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发表时间：
2004-09-01
影响因子：
5.5
通讯作者：
Taylor, PM
中科院分区：
文献类型：
--
作者：
Baird, FE;Beattie, KJ;Taylor, PM
系统N（SNAT 3和SNAT 5）氨基酸转运蛋白是谷氨酰胺跨哺乳动物细胞类型（包括肝细胞和星形胶质细胞）质膜转运的关键介质。我们证明，SNAT 5在非洲爪蟾卵母细胞中过表达时，同时显示双向谷氨酰胺通量。内流和外流都是明显的Na+依赖性的，但由于它们不直接偶联，载体能够介导净氨基酸穿过细胞膜的运动。谷氨酰胺流入和流出的表观K-m值相似（类似于1 mm），转运蛋白行为与动力学模型一致，其中载体从外向内构象（空的或装载底物的）重新定向是转运循环中的限制步骤。在灌注的大鼠肝脏中，可以通过简单的动力学模型描述流入（门）谷氨酰胺浓度和净肝谷氨酰胺通量之间的观察到的关系，假设通过系统N的流入和流出之间的平衡决定净通量，其中在生理条件下，由于细胞内谷氨酰胺浓度高，流出通常是饱和的。在大鼠肝脏中，SNAT 5显示出比SNAT 3更多的门静脉周围mRNA分布，表明SNAT 5可能对净肝谷氨酰胺通量的调节具有特别重要的意义。
System N (SNAT3 and SNAT5) amino acid transporters are key mediators of glutamine transport across the plasma membrane of mammalian cell types, including hepatocytes and astrocytes. We demonstrate that SNAT5 shows simultaneous bidirectional glutamine fluxes when overexpressed in Xenopus oocytes. Influx and efflux are both apparently Na+ dependent but, since they are not directly coupled, the carrier is capable of mediating net amino acid movement across the cell membrane. The apparent K-m values for glutamine influx and efflux are similar (similar to 1 mm) and the transporter behaviour is consistent with a kinetic model in which re-orientation of the carrier from outside- to inside-facing conformations (either empty or substrate loaded) is the limiting step in the transport cycle. In perfused rat liver, the observed relationship between influent (portal) glutamine concentration and net hepatic glutamine flux may be described by a simple kinetic model, assuming the balance between influx and efflux through System N determines net flux, where under physiological conditions efflux is generally saturated owing to high intracellular glutamine concentration. SNAT5 shows a more periportal mRNA distribution than SNAT3 in rat liver, indicating that SNAT5 may have particular importance for modulation of net hepatic glutamine flux.