Recent molecular advances in mammalian glutamine transport
Recent molecular advances in mammalian glutamine transport
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DOI：
10.1093/jn/131.9.2475s
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发表时间：
2001-09-01
影响因子：
4.2
通讯作者：
Bode, BP
中科院分区：
文献类型：
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作者：
Bode, BP
在过去的30年里，关于质膜谷氨酰胺转运蛋白在健康和疾病中的活性，包括它们在代谢中的潜在调节作用，已经有了很多了解。自20世纪60年代以来，对单个谷氨酰胺转运体的区分是基于功能特征，如底物特异性、离子依赖性、动力学和调控特性。在过去的两年中，已经从人类和啮齿动物的cDNA文库中分离出几个编码具有这些定义活性的蛋白质的基因（称为“系统”），并发现它们分布在四个不同的基因家族中。目前分离到的Na+依赖性谷氨酰胺转运蛋白基因有系统N （SN1）、系统A（ATA1, ATA2）、系统ASC/B-0 （ASCT2或ATB(0)）、系统B-0、B-+ (ATB(0,+))和系统y(+)L(y（+)LAT1, y(+)LAT2）。编码系统L（LAT1, LAT2）和系统b(0,+) （b(0,+)AT）的Na+独立谷氨酰胺转运蛋白基因最近也被分离出来，并且与y(+)L类似，已被证明具有与4F2重链（CD98）或rBAT（与b（0,+）氨基酸转运蛋白相关）的二硫连接异二聚体的功能。本文综述了它们的分子特征、催化机理和组织分布。虽然大多数这些转运体介导其他几种氨基酸的跨膜运动，但它们在调节器官间谷氨酰胺通量中的潜在作用被讨论。最重要的是，这些新分离的转运基因提供了人们期待已久的工具来研究它们在分解代谢状态下的分子调控，在这种状态下谷氨酰胺被认为是“有条件必需的”。
Much has been learned about plasma membrane glutamine transporter activities in health and disease over the past 30 years, including their potential regulatory role in metabolism. Since the 1960s, discrimination among individual glutamine transporters was based on functional characteristics such as substrate specificity, ion dependence, and kinetic and regulatory properties. Within the past two years, several genes encoding for proteins with these defined activities (termed "systems") have been isolated from human and rodent cDNA libraries and found to be distributed among four distinct gene families. The Na+-dependent glutamine transporter genes isolated thus far are System N (SN1), System A(ATA1, ATA2), System ASC/B-0 (ASCT2 or ATB(0)), System B-0,B-+ (ATB(0,+)) and System y(+)L(y(+)LAT1, y(+)LAT2). Na+-independent glutamine transporter genes encoding for System L(LAT1, LAT2) and System b(0,+) (b(0,+)AT) have also been recently isolated, and similar to y(+)L, have been shown to function as disulfide-linked heterodimers with the 4F2 heavy chain (CD98) or rBAT (related to b(0,+) amino acid transporter). In this review, the molecular features, catalytic mechanisms and tissue distributions of each are addressed. Although most of these transporters mediate the transmembrane movement of several other amino acids, their potential roles in regulating interorgan glutamine flux are discussed. Most importantly, these newly isolated transporter genes provide the long awaited tools necessary to study their molecular regulation during the catabolic states in which glutamine is considered to be "conditionally essential."