N-Glycan biosynthesis

The term ‘Glycan’ refers to oligosaccharides or polysaccharides. They also refer to glycoconjugates such as glycolipids and glycoproteins. Two different types of glycans attached to proteins are N-glycans and O-glycans. N-glycans, more precisely N-linked glycans are attached to the Asp residue of the tripeptide sequence of Asp-X-Ser/Thr (X is any amino acid except Pro) of proteins. In most eukaryotes, the N-glycan anchors are derived from a 14-sugar oligosaccharide containing 9 mannose, 3 glucose and 2 N-acetylglucosamine molecules. This process begins with the addition of 2 N-acetylglucosamine to dolichyl-phosphate in the cytoplasmic side of endoplasmic reticulum membrane. After the addition of 2 N-acetylglucosamine and 5 mannose residues, the remaining process continues in the internal side of ER. Then the enzyme oligosaccharide-protein glycosyltransferase links this glycan anchor to the above mentioned Asp residue of polypeptides in the lumen of ER. The glycan anchor can then be processed (by trimming and extension of sugar residues) to produce various types of N-glycans. This process takes place in golgi apparatus. The main processing includes removal of glucose and mannose residues and addition of N-acetylglucosamine, N-acetylneuraminic acid and fucose residues. The attachment of the glycan anchors is important for the proper folding of many proteins.

Of the enzymes required for the incorporation of 9 mannose, 2 N-acetylglucosamine and 3 glucose residues, the enzymes for the incorporation of second N-acetylglucosamine and third glucose residues are missing in Cryptosporidium parvum and Cryptosporidium hominis, whereas the enzymes for the incorporation of all three glucose residues and the second N-acetylglucosamine residues are missing in Cryptosporidium muris genome. The comparison to the N-glycan biosynthesis pathway of Toxoplasma gondii showed that the last two enzymes in T. gondii pathway catalysing the removal of 4 mannose residues and the addition of third N-acetylglucosamine residue are absent in Cryptosporidium species.

Open in a new window

Sources and fates of metabolites