Schematic diagram of GDP-L-fucose synthesis. GDP-L-fucose synthesis occurs by two cytosolic pathways, namely the de novo and salvage pathways. In de novo synthesis (A), GMD with coenzyme NADP+ removes one H2O-equivalent from GDP-D-mannose to form GDP-4-keto-6-deoxy-D-mannose. Then, GMER catalyzes epimerizations at C3 and C5 followed by an NADPH-dependent reduction of C4 to yield GDP-L-fucose. In the salvage pathway (B), Fuk transfers a single phosphate from ATP to free cytosolic L-fucose, yielding L-fucose-1-phosphate and the byproduct ADP. Next, FPGT transfers GMP from GTP to L-fucose-1-phosphate, producing GDP-L-fucose and pyrophosphate. Evidence presented here strongly supports the exclusive use of the de novo synthetic pathway in S. mansoni. GMD, GDP-D-mannose-4,6-dehydratase; GMER, GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase; Fuk, L-fucokinase; FPGT, L-fucose-1-phosphate guanylyltransferase.