GLUT1 is a highly efficient L-fucose transporter

Understanding L-fucose metabolism is important because it is used as a therapy for several congenital disorders of glyco-sylation. Exogenous L-fucose can be activated and incorporated directly into multiple N-and O-glycans via the fucose salvage/ recycling pathway. However, unlike for other monosaccharides, no mammalian L-fucose transporter has been identified. Here, we functionally screened nearly 140 annotated transporters and identified GLUT1 (SLC2A1) as an L-fucose transporter. We confirmed this assignment using multiple approaches to alter GLUT1 function, including chemical inhibition, siRNA knockdown, and gene KO. Collectively, all methods demon-strate that GLUT1 contributes significantly to L-fucose uptake and its utilization at low micromolar levels. Surprisingly, millimolar levels of D-glucose do not compete with L-fucose uptake. We also show macropinocytosis, but not other endo-cytic pathways, can contribute to L-fucose uptake and utiliza-tion. In conclusion, we determined that GLUT1 functions as the previously missing transporter component in mammalian L-fucose metabolism.