Fucose: biosynthesis and biological function in mammals

Area of Science:

• Glycobiology
• Biochemistry
• Molecular Biology

Background:

• Fucose is a deoxyhexose found across organisms.
• Fucose-containing glycans are crucial for mammalian processes including immune responses, cell adhesion, and developmental signaling.
• Aberrant fucosylated oligosaccharide expression is linked to diseases like cancer and atherosclerosis.

Purpose of the Study:

• To review the biological functions of mammalian fucosylated glycans.
• To explore the biosynthetic pathways of GDP-fucose, the precursor for fucosylated glycans.

Main Methods:

• Literature review of studies on fucose metabolism and glycan function.
• Analysis of genetic defects and their phenotypic consequences in humans and mice.
• Examination of the two primary pathways for GDP-fucose synthesis in mammalian cells.

Main Results:

• Fucose deficiency leads to complex phenotypes, exemplified by leukocyte adhesion deficiency type II (LAD II) in humans and a mouse model.
• Fucosyltransferases synthesize fucosylated glycans, utilizing GDP-fucose as a substrate.
• Mammalian cells synthesize GDP-fucose via a de novo pathway (GDP-mannose-dependent) and a salvage pathway (free fucose-dependent).

Conclusions:

• Fucosylated glycans play essential roles in diverse physiological and pathological processes in mammals.
• Understanding GDP-fucose biosynthesis is key to comprehending the functional significance of fucosylated glycans.
• Defects in fucose metabolism result in significant health disorders, underscoring the importance of this sugar.