WHAT IS GLYCOSILATION?

Glycosylation is the enzymatic process that links saccharides (also called, carbohydrates or sugars) to produce glycans (see definition), either free or attached to proteins and lipids.

This enzymatic process produces one of four fundamental components of all cells (along with nucleic acids, proteins, and lipids) and also provides a co-translational and post-translational modification mechanism that modulates the structure and function of membrane and secreted proteins.

The majority of proteins synthesized in the rough ER (check more about ER and rough ER in the definition part) undergo glycosylation.
It is an enzyme-directed site-specific process, as opposed to the non-enzymatic chemical reaction of glycation.
Glycosylation is also present in the cytoplasm and nucleus as the O-GlcNAc modification.

Six classes of glycans are produced:


N-linked glycans attached to the amide nitrogen of asparagine (Asn) side chains,

O-linked glycans attached to the hydroxy oxygen of serine (SER) and threonine (Thr ) side chains;


glycosaminoglycans attached to the hydroxy oxygen of serine;

glycolipids in which the glycans are attached to ceramide,

hyaluronan which is unattached to either protein or lipid,

and GPI anchors which link proteins to lipids through glycan linkages.









Proteins that traverse the secretory pathway of eukaryotic cells can be covalently modified with carbohydrates, which are important for their stability and folding, and which mediate diverse recognition events in growth and development.

Defects in the attachment of carbohydrate to protein give rise to mental and psychomotor retardation, dysmorphism, and blood coagulation defects.
These symptoms, referred to as CDG (for congenital disorders of glycosylation, or, until recently, for carbohydrate-deficient glycoprotein syndrome), are caused by mutations that affect the pathway for N-glycosylation.
CDGs are caused by N-glycosylation defects stemming from abnormalities in N-glycosylation site occupancy (CDG type-I) or N-glycan trimming and elongation (CDG-type II).
The abundant plasma protein transferrin, which is normally fully glycosylated, can be used as an indicator to detect protein underglycosylation.
N-linked glycosylation is the most frequent modification of secretory proteins in eukaryotic cells.

The highly conserved glycosylation process is initiated in the endoplasmic reticulum (ER), where the Glc3Man9GlcNAc2 oligosaccharide is assembled on the lipid carrier dolichylpyrophosphate and then transferred to selected asparagine residues of polypeptide chains.
In recent years, several inherited human diseases, congenital disorders of glycosylation (CDG), have been associated with deficiencies in this pathway.
The ER-associated glycosylation pathway has been studied in the budding yeast Saccharomyces cerevisiae, and this model system has been invaluable in elucidating the molecular basis of novel types of CDG.