Alpha-L-fucosidase (FUCA1)

Alpha-L-fucosidase (FUCA1) is a lysosomal hydrolase (EC 3.2.1.51) responsible for the removal of terminal L-fucose residues from glycoproteins and glycolipids (UniProt P04066). It plays a critical role in the catabolism of complex glycoconjugates; a genetic deficiency in this enzyme leads to Fucosidosis, a rare and severe lysosomal storage disorder characterized by neurological deterioration and organomegaly (NIH GARD). In oncology, elevated serum levels of alpha-L-fucosidase serve as a significant diagnostic biomarker for hepatocellular carcinoma (HCC), often demonstrating higher sensitivity than alpha-fetoprotein for early-stage detection (PubMed: 25143918). While not currently a primary target for approved small-molecule therapeutics, the enzyme is a focus for the development of iminosugar-based inhibitors like deoxyfuconojirimycin, which are used as research tools and potential chemical chaperones (PubChem CID 123600). Therapeutic challenges include the requirement for high selectivity to avoid interfering with other glycosidases and the difficulty of ensuring effective drug delivery to the lysosomal compartment.

Other names

Alpha-L-fucoside fucohydrolaseFUCAL-fucosidaseAlpha-L-fucosidase 1AFU

Competitive inhibition of the enzyme active site to prevent the hydrolytic cleavage of terminal fucose residues from glycoconjugates.