By: Richard D. Cummings
Five of the most famous giant polysaccharides produced by microbes, plants, and animals are peptidoglycan, starch, cellulose, chitin, and hyaluronic acid (hyaluronan, HA). Consistent with this, five of the most common nucleotide sugars in nature are the precursors to these polysaccharides, and include ADP-glucose (ADP-Glc), UDP-glucose (UDP-Glc), UDP-glucuronate (UDP-GlcA), UDP-N-acetylmuramic acid (UDP-MurNAc), and UDP-N-acetylglucosamine (UDP-GlcNAc). In plants, ADP-Glc is used largely for starch synthesis (1), whereas UDP-Glc is used for cellulose in plants and also for glycogen synthesis in animals. In the brain, UDP-GlcNH2 is used as a donor to place glucosamine within glycogen there (2). Peptidoglycan is made from UDP-MurNAc and UDP-GlcNAc. In animals, hyaluronan is an exceptional polysaccharide, as it is generated from UDP-GlcNAc and UDP-GlcA without linkage to a protein carrier precursor. HA is found extracellularly in animal cells and bacteria, and it is the only one that is normally synthesized in the plasma membrane of animal cells. It is made by the HAS enzyme that is positioned in the plasma membrane and uses the donors UDP-GlcA and UDP-GlcNAc in alternating fashion to create the GlcA-GlcNAc repeating disaccharide in hyaluronan (3-5). It is also likely that HAS first synthesizes short chitin oligomers GlcNAc-(GlcNAc)n that help initiate the synthesis of the polysaccharide, which oddly grows from the reducing end (6,7). This is odd because all other polysaccharides in mammals grow from the non-reducing end, except those that occur in proteoglycans and the glycan is linked to serine. The length of a typical hyaluronan molecule may exceed 25,000 disaccharide repeats in length and millions of daltons in size and a length up to ∼10 µm (3,8). The naked mole rate has a high level of hyaluronan, associated with its reduced likelihood of developing cancer (9), as well as a long life expectancy (10-30 years), which may in part be attributed to its fantastic rate of production of hyaluronan (10). Engineered overexpression of hyaluronan in a mouse also extends its lifespan (10).
What are the most abundant polysaccharides on earth? No one has measured this of course, but here is an educated guess. Cellulose (a linear polymer of Glc in β-1-4 linkage) is likely to be first place as the most abundant polysaccharide on earth, as it occurs in all plants. The ranking of other polysaccharides is often disputed. Perhaps hemicelluloses (branched cellulose with various monosaccharides attached, e.g., xylose, mannose, galactose) is in second place, and it is likely that xylans (polymers of Xyl in β-1-4 linkage and branched with monosaccharides e.g., GlcA and arabinose) are in third place, although some might argue xylans are in second place. But who is in fourth and fifth place? This might belong to peptidoglycan in microbes, or to chitin. Chitin is a β-1-4 GlcNAc repeating polysaccharide, and is found in many bacteria, all fungi, insects, and all crustaceans. [Of course, some might argue that chitin is actually second place, and xylans are third.]. But chitin oligosaccharides, as in disaccharides, occur in animal cells and make up the core structure of all N-glycans (11). Short chitin oligosaccharides are also found in glycans of parasites (12). Chitin is extremely interesting in its abundance. E.O. Wilson has stated that ants alone make up 2/3 of all the biomass of insects on earth, and chitin is a major part of both ants and termites (the latter make up a large amount of our earth’s insect biomass) (13).
Starches and glycogen contain polymers of ⍺-linked glucose (Glc⍺1-4Glc)n, and these are common in both plants and animals; they can also be branched with Glc⍺1-6 side chains. Interestingly, glucose also occurs in ⍺-linkage in N-glycans of fungi, plants and most animals; the glucose trisaccharide Glc⍺1-2Glc⍺1-3Glc⍺1-3Man⍺1-2Man-R occurs in N-glycans during their biosynthesis, but is completely removed after glycoproteins are matured in the ER/Golgi (11).
References
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