Processing pathway for non-lysosomal glycoproteins

After the processing in the Golgi, three types of N-linked oligosaccharides are formed :

  1. High-mannose type
  2. Complex type
  3. Hybrid type

The overall synthesis process is controlled by specific enzymes which act in the proper order and time, and are present in different amounts and in the respective Golgi compartment.

Each specific cell type in an organism contains its own specific processing enzymes. The result is that the same protein produced by individual cell types may have different carbohydrate chains.

For example certain Asn residues in HA (haemagglutinin) of influenza virus have complex type oligosaccharides when the virus is grown in one cell type but high-mannose oligosaccharides when the virus is grown in another cell type.


The high-mannose oligosaccharides have the same structures as the intermediates which are formed during the processing of complex oligosaccharides : (Man)8 (GlcNAc)2 , (Man)7 (GlcNAc)2 , (Man)6 (GlcNAc)2 , (Man)5 (GlcNAc)2. They occur after trimming by Mannosidase I (alpha1,2 specific) in the cis-Golgi.


The exception is (Man)8 (GlcNAc)2 which is not cleaved by the enzyme. Possibly the part of the oligosaccharide is buried in a creavasse in the protein surface and thus is not available for mannosidase.


The complex type oligosaccharides are formed after the further processing of (GlcNAc)2 (Man)5 by specific enzymes. This precursor is at first transported from cis- to the medial-Golgi compartment. Then:
a.)N-Acetylglucosaminyltransferase I adds a GlcNAc residue to the terminal mannose residue.
b.)Mannosidase II (alpha 1,3/6 specific) removes two mannose residues
c.)N-Acetylglucosaminyltransferase II adds one GlcNAc residue and fucosyltransferase can add fucose residue but only when there is GlcNAc linked (beta 1,2) to the mannose (alpha 1,3) branched.


Further processing occurs in the trans-Golgi :

d.)N-Acetylglucosaminyltransferase IV adds GlcNAc residue to the mannose residue (then the oligosaccharide is higher branched). Higher branched (tri-, tetra_ and pentaantennary ) complex type oligosaccharides are formed by the subsequent addition of further GlcNAc residues by the corresponding transferases to the mannose residues. The type is determined by the order of action of the different N-Acetylglucosaminyltransferases.
e.)Galactosyltransferase adds galactose residues to the terminal GlcNAc residues.
f.)Sialyltransferase adds sialic acid residues which become the terminal part of the oligosaccharide (they are thought to protect the glycoprotein from degradation).


Sialic acid can be linked either (alpha 2,6) or (alpha 2,3) to the galactose residues. It could be also linked (alpha 2,8/9) to another preceeding sialic acid residue forming large sialic acid clusters (for example up to 55 in N-CAMs - neural cells adhesion molecules). The sialic acid polymers are found predominantly in neurons.


The hybrid type oligosaccharides are synthesized when the N-Acetylglucosaminyltransferase III acts prior to the action of Mannosidase II (in medial-Golgi compartment). GlcNAc-T III adds GlcNAc residue which is linked (beta 1,4) to the core mannose residue. It prevents the action of mannosidase II.

Then in the trans-Golgi galactose and sialic acid residues are added.


The carbohydrate chains of different types can undergo additional modifications such as sulphation, phosphorylation or acetylation.


Go to :

Pathway for lysosomal enzymes

N-glycosylation

Biosynthesis of GPI membrane anchors

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