GDP-L-fucose synthase (GFUS)

GDP-L-fucose synthase (GFUS) is an NADPH-dependent enzyme that catalyzes the terminal step of the *de novo* biosynthesis of GDP-L-fucose from GDP-4-keto-6-deoxy-D-mannose, involving both epimerization and reduction reactions[1][3][5]. This reaction is essential because GDP-L-fucose serves as a donor for the fucosylation of N- and O-glycans, a modification critical for the function of many glycoproteins and glycolipids, including those involved in cell adhesion (e.g., selectin ligands), immune function, and developmental processes[2][4][5]. Mutations in the GFUS gene lead to a rare congenital disorder of glycosylation (GFUS-CDG), resulting in global protein hypofucosylation and associated symptoms such as developmental delay, growth impairment, and immunological defects. Oral supplementation with L-fucose can compensate for defective *de novo* synthesis by activating the salvage pathway, restoring cellular fucosylation and improving clinical symptoms[2]. GFUS, through its role in glycoprotein modification, may have additional implications for inflammatory diseases, auto-immunity, and cancer, though direct targeting for these indications remains investigational[1].

Other names

GFUSGDP-L-fucose synthaseTSTA3FX proteinSDR4E1P35BGDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductaseGDP-4-keto-6-deoxy-D-mannose epimerase-reductaseRed cell NADP(H)-binding proteinShort-chain dehydrogenase/reductase family 4E member 1Tissue specific transplantation antigen 3Testis tissue sperm-binding protein Li 45a

Enzyme replacement or substrate supplementation (L-fucose enables salvage pathway for GDP-L-fucose generation in deficiency)[2]