Carbohydrates and human glycosylation

Glycosylation is one of the most abundant, diverse, and complex forms of posttranslational modification (PTM) shared among nearly all unicellular to multicellular prokaryotic and eukaryotic organisms. The uniqueness of glycosylation PTM stems from the fact that, unlike other forms of PTMs, this phenomenon creates highly dynamic and complex glycan structures depending on the species, the cell type, and the environmental conditions. Involving complex metabolic networks and enzymatic pathways, glycosylation exponentially increases biological complexity and implicates itself in many health and disease functions. It is often regarded as an evolutionary adaptation to bring about a significant expansion in biomolecules without requiring a direct genetic template. Sharing commonalities in glycan synthesis, species-specific glycan structures are generated by the presence of unique sets of enzymes and acceptor substrates across species. However, across organisms, glycosylation plays a crucial role as a structural and functional determinant of the generated glycoconjugates owing to its regulatory control on fundamental aspects of biomolecules such as stability, folding, distribution, and activity. This regulatory control, exerted by the highly dynamic and complex glycoconjugate structures, is spatially organized in both the extracellular and intracellular compartments. This chapter details an overview of the human glycosylation machinery involved in the synthesis and recycling of diverse glycoconjugate structures.