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Evolution and Diversity of Glycomolecules from Unicellular Organisms to Humans

Richard D. Cummings
Richard D. Cummings
   | Apr 11, 2024
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Article Category: Review
Published Online: Apr 11, 2024
Page range: 1 - 35
DOI: https://doi.org/10.2478/biocosmos-2024-0001
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© 2024 Richard D. Cummings, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1.

Here is depicted a few examples of the diversity of glycans found in glycomolecules of different organisms – mycobacteria, yeast, plants, nematodes, and humans. More details about these structures and discussions about their biosynthesis and function can be found in the following references (5,6,7,8,9,10,11,12). For more information about the symbols above used to designate monosaccharides see https://www.ncbi.nlm.nih.gov/glycans/snfg.html. Hundreds of different monosaccharides are known, and they can be found in multiple and unique combinations in all forms of life (13, 14). As depicted, the monosaccharide linkages are either α or β, and the linkage number, e.g., 2, 3, or 4, etc., refers to the carbon number on the monosaccharide to which the preceding monosaccharide is linked. Asn, asparagine.
Here is depicted a few examples of the diversity of glycans found in glycomolecules of different organisms – mycobacteria, yeast, plants, nematodes, and humans. More details about these structures and discussions about their biosynthesis and function can be found in the following references (5,6,7,8,9,10,11,12). For more information about the symbols above used to designate monosaccharides see https://www.ncbi.nlm.nih.gov/glycans/snfg.html. Hundreds of different monosaccharides are known, and they can be found in multiple and unique combinations in all forms of life (13, 14). As depicted, the monosaccharide linkages are either α or β, and the linkage number, e.g., 2, 3, or 4, etc., refers to the carbon number on the monosaccharide to which the preceding monosaccharide is linked. Asn, asparagine.

Figure 2.

Modifications of proteins with carbohydrates can increase both the complexity and size, as illustrated here for simple sugar modifications of the amino acid serine, as often seen in O-glycans of animals. While the largest one shown here has a tetrasaccharide attached, some O-glycans in animals can reach enormous sizes and contain many hundreds of monosaccharide moieties. Moreover, multiple serine, threonine or tyrosine residues may also be O-glycosylated on a single protein, thus further enhancing diversity and size.
Modifications of proteins with carbohydrates can increase both the complexity and size, as illustrated here for simple sugar modifications of the amino acid serine, as often seen in O-glycans of animals. While the largest one shown here has a tetrasaccharide attached, some O-glycans in animals can reach enormous sizes and contain many hundreds of monosaccharide moieties. Moreover, multiple serine, threonine or tyrosine residues may also be O-glycosylated on a single protein, thus further enhancing diversity and size.

Figure 3.

Examples of formose reactions leading to the generation of d-ribose from formaldehyde. The generation of glycolaldehyde, glyceraldehyde and their condensation can lead to the formation of the 5-carbon pentulose, a ketose, which can epimerize to the straight chain aldose d-ribose, which itself is in equilibrium with its ring form, as shown for β-d-ribose. See the text and references therein for a more complete discussion of the origin and interconversions of monosaccharides.
Examples of formose reactions leading to the generation of d-ribose from formaldehyde. The generation of glycolaldehyde, glyceraldehyde and their condensation can lead to the formation of the 5-carbon pentulose, a ketose, which can epimerize to the straight chain aldose d-ribose, which itself is in equilibrium with its ring form, as shown for β-d-ribose. See the text and references therein for a more complete discussion of the origin and interconversions of monosaccharides.

Figure 4.

Cells are bounded by membranes and glycomolecules are typically on the outer membrane of cells or secreted from the cells; however, the precursors to such glycomolecules are formed in the cytoplasm. One approach found in all organisms to overcome this topological barrier is to generate unique types of lipid-linked sugars. Within the cytoplasmic side of a membrane, cells can generate a lipid-linked sugar, and it can then be flipped to the opposite side (external or lumenal). In the two examples, taken from animal cells, but common to eukaryotes, glucosylceramide is synthesized on the cytoplasmic side of the Golgi apparatus using UDP-glucose as a donor, and the product is then flipped to the lumen of the Golgi by protein-assisted pathways. Similarly, for N-glycosylation pathways in animals, one example is shown here. The dolichol-pyrophosphoryl-GlcNAc2Man4 is synthesized on the cytoplasmic face of the ER, and finally modified to dolichol-pyrophosphoryl-GlcNAc2Man5 through the donor GDP-mannose. This particular product is then flipped to the ER lumen for further modifications there and eventual transfer of its preformed oligosaccharide to the newly synthesized protein, either co- or post-translationally. This basic concept of such topological resolutions also occurs in prokaryotes, as seen for LPS. Also shown is the direct synthesis at the plasma membrane of HA in both prokaryotes and eukaryotes using cytoplasmic precursors and extrusion of the product into the extracellular space. ER, endoplasmic reticulum; GlcNAc, N-acetylglucosamine; HA, hyaluronic acid; LPS, lipopolysaccharides.
Cells are bounded by membranes and glycomolecules are typically on the outer membrane of cells or secreted from the cells; however, the precursors to such glycomolecules are formed in the cytoplasm. One approach found in all organisms to overcome this topological barrier is to generate unique types of lipid-linked sugars. Within the cytoplasmic side of a membrane, cells can generate a lipid-linked sugar, and it can then be flipped to the opposite side (external or lumenal). In the two examples, taken from animal cells, but common to eukaryotes, glucosylceramide is synthesized on the cytoplasmic side of the Golgi apparatus using UDP-glucose as a donor, and the product is then flipped to the lumen of the Golgi by protein-assisted pathways. Similarly, for N-glycosylation pathways in animals, one example is shown here. The dolichol-pyrophosphoryl-GlcNAc2Man4 is synthesized on the cytoplasmic face of the ER, and finally modified to dolichol-pyrophosphoryl-GlcNAc2Man5 through the donor GDP-mannose. This particular product is then flipped to the ER lumen for further modifications there and eventual transfer of its preformed oligosaccharide to the newly synthesized protein, either co- or post-translationally. This basic concept of such topological resolutions also occurs in prokaryotes, as seen for LPS. Also shown is the direct synthesis at the plasma membrane of HA in both prokaryotes and eukaryotes using cytoplasmic precursors and extrusion of the product into the extracellular space. ER, endoplasmic reticulum; GlcNAc, N-acetylglucosamine; HA, hyaluronic acid; LPS, lipopolysaccharides.

Figure 5.

Evolving nature of glycan structures by the host which may be recognized by an invading organism. In this host vs invader model, the host may survive by modifying the glycans, e.g., glycan 1 to glycan 2, to which the invader may not bind well. The invader or other invaders may evolve the ability to bind the new glycan, leading the host to again respond with a modified glycan, e.g., glycan 3 or 4. This cycle may be endless, and leads to great diversity and complexity of both glycans through time on the host and multiple types of binders produced by the invaders.
Evolving nature of glycan structures by the host which may be recognized by an invading organism. In this host vs invader model, the host may survive by modifying the glycans, e.g., glycan 1 to glycan 2, to which the invader may not bind well. The invader or other invaders may evolve the ability to bind the new glycan, leading the host to again respond with a modified glycan, e.g., glycan 3 or 4. This cycle may be endless, and leads to great diversity and complexity of both glycans through time on the host and multiple types of binders produced by the invaders.
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