Guanosine diphosphate fucose (GDP-fucose) (GDP-fucose)

GDP-fucose (Guanosine diphosphate fucose) is a critical nucleotide sugar that serves as the sole donor substrate for all fucosyltransferase enzymes in eukaryotic cells [PubChem CID 161167]. It is synthesized through two distinct metabolic routes: the de novo pathway from GDP-mannose and the salvage pathway from free fucose [PubMed: 28811311]. Once produced, it is transported into the Golgi apparatus by the SLC35C1 transporter to facilitate the fucosylation of proteins and lipids [UniProt: Q96A29]. This modification is essential for biological processes such as leukocyte trafficking via selectin ligands and the regulation of Notch signaling [PubMed: 16040618]. In many cancers, elevated GDP-fucose levels drive the expression of fucosylated glycans like Sialyl Lewis X, which promote tumor metastasis and immune evasion [PubMed: 30217950]. Conversely, genetic defects in the synthesis or transport of GDP-fucose result in Leukocyte Adhesion Deficiency type II (LAD II), characterized by severe immunodeficiency [NCBI: NBK1397]. Therapeutic targeting of this molecule primarily involves the use of small molecule inhibitors like 2-fluorofucose (2-FF), which deplete the intracellular GDP-fucose pool [PubMed: 23939470]. By reducing the availability of this substrate, these drugs can decrease the fucosylation of oncogenic receptors and improve the efficacy of monoclonal antibody therapies [PubMed: 28811311]. Monitoring fucosylated biomarkers, such as AFP-L3, serves as a clinical tool for assessing disease progression and the metabolic state of the fucosylation pathway [PubMed: 15173233].

Other names

GDP-L-fucoseGuanosine 5'-(beta-L-fucopyranosyl diphosphate)GDP-FucGuanosine diphosphofucose

Depletion of the intracellular GDP-fucose pool through inhibition of the de novo synthesis pathway (specifically GMDS) and competitive inhibition of fucosyltransferases.