The terms glycans and polysaccharides are defined by IUPAC as synonyms meaning "compounds consisting of a large number of monosaccharides linked glycosidically".<ref>{ { cite book | title=IUPAC Gold Book - Glycans | chapter-url=http://goldbook.iupac.org/G02645.html| doi=10.1351/goldbook.G02645| chapter=Glycans| year=2009| isbn=978-0-9678550-9-7}}</ref> However, in practice the term glycan may also be used to refer to the carbohydrate portion of a glycoconjugate, such as a glycoprotein, glycolipid, or a proteoglycan, even if the carbohydrate is only an oligosaccharide. Glycans usually consist solely of O-glycosidic linkages of monosaccharides. For example, cellulose is a glycan (or, to be more specific, a glucan) composed of β-1,4-linked D-glucose, and chitin is a glycan composed of β-1,4-linked N-acetyl-D-glucosamine. Glycans can be homo- or heteropolymers of monosaccharide residues, and can be linear or branched.
Glycans and proteins
Glycans can be found attached to proteins as in glycoproteins and proteoglycans. In general, they are found on the exterior surface of cells. O- and N-linked glycans are very common in eukaryotes but may also be found, although less commonly, in prokaryotes.
N-Linked glycans
Introduction
N-Linked glycans are attached in the endoplasmic reticulum to the nitrogen (N) in the side chain of asparagine (Asn) in the sequon. The sequon is an Asn-X-Ser or Asn-X-Thr sequence, where X is any amino acid except proline and the glycan may be composed of N-acetylgalactosamine, galactose, neuraminic acid, N-acetylglucosamine, fucose, mannose, and other monosaccharides.
Assembly
In eukaryotes, N-linked glycans are derived from a core 14-sugar unit assembled in the cytoplasm and endoplasmic reticulum. First, two N-acetylglucosamine residues are attached to dolichol monophosphate, a lipid, on the external side of the endoplasmic reticulum membrane. Five mannose residues are then added to this structure. At this point, the partially finished core glycan is flipped across the endoplasmic reticulum membrane, so that it is now located within the reticular lumen. Assembly then continues within the endoplasmic reticulum, with the addition of four more mannose residues. Finally, three glucose residues are added to this structure. Following full assembly, the glycan is transferred en bloc by the glycosyltransferase oligosaccharyltransferase to a nascent peptide chain, within the reticular lumen. This core structure of N-linked glycans, thus, consists of 14 residues (3 glucose, 9 mannose, and 2 N-acetylglucosamine).
Image: https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=glyco.figgrp.469
Dark squares are N-acetylglucosamine; light circles are mannose; dark triangles are glucose.
Processing, modification, and diversity
Once transferred to the nascent peptide chain, N-linked glycans, in general, undergo extensive processing reactions, whereby the three glucose residues are removed, as well as several mannose residues, depending on the N-linked glycan in question. The removal of the glucose residues is dependent on proper protein folding. These processing reactions occur in the Golgi apparatus. Modification reactions may involve the addition of a phosphate or acetyl group onto the sugars, or the addition of new sugars, such as neuraminic acid. Processing and modification of N-linked glycans within the Golgi does not follow a linear pathway. As a result, many different variations of N-linked glycan structure are possible, depending on enzyme activity in the Golgi.
Functions and importance
N-linked glycans are extremely important in proper protein folding in eukaryotic cells. Chaperone proteins in the endoplasmic reticulum, such as calnexin and calreticulin, bind to the three glucose residues present on the core N-linked glycan. These chaperone proteins then serve to aid in the folding of the protein that the glycan is attached to. Following proper folding, the three glucose residues are removed, and the glycan moves on to further processing reactions. If the protein fails to fold properly, the three glucose residues are reattached, allowing the protein to re-associate with the chaperones. This cycle may repeat several times until a protein reaches its proper conformation. If a protein repeatedly fails to properly fold, it is excreted from the endoplasmic reticulum and degraded by cytoplasmic proteases.