Kilberg M S, Handlogten M E, Christensen H N
J Biol Chem. 1980 May 10;255(9):4011-9.
In the rat hepatocyte, whether freshly separated or in primary culture, we do not find L-glutamine entry by Systems A and ASC as seen in cells previously studied. Instead the mediated entry of glutamine appears to occur exclusively by a Na+-dependent system ("N") apparently specific to amino acid amides and L-histidine; however, a portion of asparagine uptake occurs by System A. The simplest evidence for the separateness of the added system is the failure of model substrates for System A (e.g. N-methylalanine) to inhibit glutamine uptake significantly, and the failure of glutamine to inhibit the uptake of L-cysteine, model substrate for System ASC, at least in this cell. As is the case for cysteine, glutamine inhibits transport by System A (although not competitively), even though showing no transport by that system. Our finding confirms an earlier inference that glutamine uptake by this cell may follow a route not taken by alanine or serine, and explains the apparently erroneous companion inference that glutamine also shares a route with these two amino acids. Its uptake has now been characterized to show a series of differences from Systems A and ASC. Especially significant in view of the importance of glutamine metabolism are an insensitivity of the new system to stimulation by either insulin or glucagon, and its distinct enhancement (not as large as that for System A) on starvation of the cells with respect to amino acids. Hence, a second system has been found to show adaptive regulation.
在大鼠肝细胞中，无论是刚分离的还是原代培养的，我们都未发现如先前研究的细胞中那样通过系统A和系统ASC进行L-谷氨酰胺的摄取。相反，谷氨酰胺的介导摄取似乎完全通过一种明显对氨基酸酰胺和L-组氨酸特异的Na⁺依赖性系统（“N”）发生；然而，一部分天冬酰胺的摄取是通过系统A进行的。支持该新增系统独立性的最简单证据是，系统A的模型底物（如N-甲基丙氨酸）不能显著抑制谷氨酰胺的摄取，并且谷氨酰胺至少在这种细胞中不能抑制系统ASC的模型底物L-半胱氨酸的摄取。与半胱氨酸的情况一样，谷氨酰胺虽不通过系统A转运，但能抑制该系统的转运（尽管不是竞争性抑制）。我们的发现证实了一个较早的推断，即该细胞摄取谷氨酰胺可能遵循一条丙氨酸或丝氨酸未采用的途径，并解释了一个明显错误的相关推断，即谷氨酰胺也与这两种氨基酸共享一条途径。现在已确定其摄取表现出与系统A和系统ASC的一系列差异。鉴于谷氨酰胺代谢的重要性，尤其显著的是新系统对胰岛素或胰高血糖素的刺激不敏感，以及在细胞氨基酸饥饿时其摄取明显增强（不如系统A增强得大）。因此，已发现第二个系统表现出适应性调节。
