Fucose: biosynthesis and biological function in mammals

Abstract

Fucose is a deoxyhexose that is present in a wide variety of organisms. In mammals, fucose-containing glycans have important roles in blood transfusion reactions, selectin-mediated leukocyte-endothelial adhesion, host-microbe interactions, and numerous ontogenic events, including signaling events by the Notch receptor family. Alterations in the expression of fucosylated oligosaccharides have also been observed in several pathological processes, including cancer and atherosclerosis. Fucose deficiency is accompanied by a complex set of phenotypes both in humans with leukocyte adhesion deficiency type II (LAD II; also known as congenital disorder of glycosylation type IIc) and in a recently generated strain of mice with a conditional defect in fucosylated glycan expression. Fucosylated glycans are constructed by fucosyltransferases, which require the substrate GDP-fucose. Two pathways for the synthesis of GDP-fucose operate in mammalian cells, the GDP-mannose-dependent de novo pathway and the free fucose-dependent salvage pathway. In this review, we focus on the biological functions of mammalian fucosylated glycans and the biosynthetic processes leading to formation of the fucosylated glycan precursor GDP-fucose.

The “less-is-more” in therapeutic antibodies: Afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity

“…A total of 13 fucosyltransferases (FUT) that have been identified in the human genome transfer a fucose residue from GDP-fucose to an acceptor substrate 24 . FUT1 and FUT2 transfer the fucose residue to the terminal galactose and form an α1,2 linkage.…”

“…The de novo pathway, which generates the majority of GDP-fucose, involves the conversion of GDP-mannose to GDP-fucose by GDP-mannose 4,6 dehydratase (GMD) and GDP-keto-6-deoxymannose 3,5-epimerase/4 reductase (also known as FX) 55 . The salvage pathway, which accounts for only a small percentage of GDP-fucose production, utilizes free cytosolic fucose derived from degraded glycoproteins or glycolipids or exogenous fucose 24 . The GDP-fucose synthesized in the cytosol must be transported into the Golgi apparatus or the endoplasmic reticulum (ER) by specific transporters in order to serve as the substrate for fucosylation reactions.…”

Efficacy of nanoceria for periodontal tissues alteration in glutamate-induced obese rats—multidisciplinary considerations for personalized dentistry and prevention

“…Periodontium connective tissue is a source of number of potentially routine biomarkers in diagnosing oral pre-malignant conditions, lesions, and malignancies [25], e.g., fucose and protein bound hexoses can be used as markers. Fucose is a deoxyhexose that is present in a wide variety of mammals; fucose-containing glycans have important roles in blood transfusion reactions, selectin-mediated leukocyte-endothelial adhesion, host-microbe interactions, and numerous ontogenic events, including signaling events by the Notch receptor family [25]. Fucoproteins and proteoglycans of connective tissue with serum glycoconjugates can be diagnostic and or prognostic marker in oral submucous fibrosis (OSMF), Leukoplakia and Oral Cancer, do have a significant diagnostic and prognostic value in these diseases [26].…”

“…This anatomical complex is vulnerable to infections, chronic inflammation, and periodontal destruction leading to loosening or loss of teeth. Molecular matrix in periodontal connective tissue is a source of number of potential biomarkers [9,[23][24][25][26][27].…”

Fucose content of monoclonal antibodies can be controlled by culture medium osmolality for high antibody-dependent cellular cytotoxicity

“…balance is generally regarded as critical in cell culture. Although it was unexpected that fucose supplementation did not increase fucosylation levels (i.e., decrease the deFuc%), it is known that GDP-fucose, the substrate for fucosylation, is derived mainly (90%) from GDPmannose (Becker and Lowe 2003). The conversion of free fucose (transported into the cytosol from extracellular medium or from lysosomes after catabolism of fucosylated glycans) to GDP-fucose is a minor salvage pathway, which explains why the addition of fucose resulted only in an increase in osmolality.…”