Understanding L-fucose metabolism is important because it is used as a therapy for several congenital disorders of glycosylation. 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 demonstrate 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 endocytic pathways, can contribute to L-fucose uptake and utilization. In conclusion, we determined that GLUT1 functions as the previously missing transporter component in mammalian L-fucose metabolism.

了解 L-岩藻糖代谢非常重要，因为它被用作多种先天性糖基化疾病的治疗方法。外源 L-岩藻糖可以被激活并通过岩藻糖回收/再循环途径直接掺入多种 N-和 O-聚糖中。然而，与其他单糖不同的是，尚未鉴定出哺乳动物 L-岩藻糖转运蛋白。在这里，我们对近 140 个带注释的转运蛋白进行了功能筛选，并将 GLUT1 ( SLC2A1 ) 鉴定为 L-岩藻糖转运蛋白。我们使用多种改变 GLUT1 功能的方法（包括化学抑制、siRNA 敲低和基因敲除）证实了这一分配。总的来说，所有方法都表明 GLUT1 对 L-岩藻糖的摄取及其在低微摩尔水平下的利用有显着贡献。令人惊讶的是，毫摩尔水平的 D-葡萄糖不会与 L-岩藻糖的吸收竞争。我们还表明巨胞饮作用（但不是其他内吞途径）可以促进 L-岩藻糖的摄取和利用。总之，我们确定 GLUT1 在哺乳动物 L-岩藻糖代谢中充当先前缺失的转运蛋白成分。