Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, CH-3012 Bern, Switzerland.
Division of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Trends Biochem Sci. 2018 Oct;43(10):752-789. doi: 10.1016/j.tibs.2018.05.003. Epub 2018 Aug 31.
Amino acid transporters (AATs) are membrane-bound transport proteins that mediate transfer of amino acids into and out of cells or cellular organelles. AATs have diverse functional roles ranging from neurotransmission to acid-base balance, intracellular energy metabolism, and anabolic and catabolic reactions. In cancer cells and diabetes, dysregulation of AATs leads to metabolic reprogramming, which changes intracellular amino acid levels, contributing to the pathogenesis of cancer, obesity and diabetes. Indeed, the neutral amino acid transporters (NATs) SLC7A5/LAT1 and SLC1A5/ASCT2 are likely involved in several human malignancies. However, a clinical therapy that directly targets AATs has not yet been developed. The purpose of this review is to highlight the structural and functional diversity of AATs, their diverse physiological roles in different tissues and organs, their wide-ranging implications in human diseases and the emerging strategies and tools that will be necessary to target AATs therapeutically.
氨基酸转运蛋白（AATs）是一种膜结合转运蛋白，可介导氨基酸进出细胞或细胞细胞器。AATs 具有多种功能作用，从神经传递到酸碱平衡、细胞内能量代谢以及合成代谢和分解代谢反应。在癌细胞和糖尿病中，AATs 的失调导致代谢重编程，改变细胞内氨基酸水平，导致癌症、肥胖和糖尿病的发病机制。事实上，中性氨基酸转运蛋白（NATs）SLC7A5/LAT1 和 SLC1A5/ASCT2 可能参与了几种人类恶性肿瘤。然而，尚未开发出直接针对 AATs 的临床治疗方法。本综述的目的是强调 AATs 的结构和功能多样性、它们在不同组织和器官中的多种生理作用、它们在人类疾病中的广泛影响以及靶向 AATs 治疗所需的新兴策略和工具。
