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.

This pathway was not reconstructed for Plasmodium falciparum in MPMP. This pathway is reconstructed with KEGG reference pathway of N-glycan biosynthesis as template for Coccidians Toxoplasma gondii and Neospora caninum. The analysis of T. gondii and N. caninum gene models showed that it has all the enzymes necessary for the formation of 14-sugar core anchor from dolichyl-phosphate. The enzyme which catalyses N-linked glycosylation (oligosaccharide-protein glycosyltransferase) is also present. In addition they also possess the enzymes for the trimming of 3 glucose residues and this forms high-mannose oligosaccharide N-glycans. Except MAN1, all the enzymes required for the removal of 4 mannose residues and addition one more N-acetylglucosamine sugar (forms complex oligosaccharide N-glycans) is also present in the gene models. The two enzymes which are present in P. falciparum (dolichol metabolism pathway) and involved in conversion of dolichol phosphate from dolichol (dolichol kinase) and dolichol diphosphate (dolichyldiphosphatase) were absent in the release 7 gene models of T. gondii and N. caninum. Of these, dolichol kinase was recently identifiedin release 8 gene models of T. gondii and it also has an ortholog in N. caninum.

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Sources and fates of metabolites