By: Richard D. Cummings
Most, if not all, of the carbohydrates and glycans in animals are reducing glycans in their free form, either as they are generated, e.g., milk sugars, or upon release from proteins or lipids. However, there are many non-reducing sugars in nature, so far mostly found in plants. By definition there are no free carbonyl groups in a non-reducing sugar, and they are in acetal or ketal form, and lack the ability to mutarotate polarized light. Thus, non-reducing sugars do not react with reagents that react with aldehyde or keto groups. Non-reducing sugars include the very important disaccharide, sucrose, a disaccharide of Glc-Fru (Glcα1-2βFruf or α-D-glucopyranosyl-1,2-D-fructofuranose), in which the Glc and Fru are joined at their anomeric carbons, head-to-head, so to speak. Other small, free glycans are extensions of sucrose with other sugars, and include raffinose (a trisaccharide of Gal α1-6-linked to sucrose), gentianose (a trisaccharide of Glc β1-6-linked to sucrose), stachyose (a tetrasaccharide of Gal-Gal linked to sucrose (Galα1-6Galα1-6Glcα1-2βFruf), and verbascose (a pentasaccharide of Gal-Gal-Gal linked to sucrose as in Galα1-6Galα1-6Galα1-6Glcα1-2βFruf) (1). The Gal residues in these sugars as indicated is α1,6-linked, and these types of sugars occur in many types of legumes (beans), but are also present in broccoli, cabbage, and brussel sprouts. Interestingly, human intestines lack an α-galactosidase, leading to the sugars gaining access to the large intestine. There, the galactose is released from the α-Gal-containing sugars by the intestinal flora and leading to bloating and the production of unpleasant gases (hydrogen sulfide, methane, nitrogen, carbon dioxide) (See: https://www.hopkinsmedicine.org/health/conditions-and-diseases/gas-in-the-digestive-tract).
Another famous and very common non-reducing disaccharide is trehalose (disaccharide of Glc-Glc as in Glcα1-1αGlc), also linked through their anomeric carbons. Trehalose is a very unusual disaccharide - very acid stable, resistant to α-glucosidases, and requires a specific enzyme ‘trehalase’ for its degradation (2). Interestingly, trehalose is considered a useful ‘cryoprotectant’ and is often used in nature for that role, as seen in the resurrection plant (Selaginella lepidophylla) and in brine shrimp embryos, where the dry weight of the organisms can reach 10-15% trehalose, allowing them to be desiccated, and rise to life again upon addition of water! Trehalose is also synthesized by microbes, especially by Mycobacterium tuberculosis, where its synthesis is essential to viability (3). Trehalose is also used in commercial products, especially in drug formulations, as a cryoprotectant and as a preservative (4,5).
References
1. Sanyal, R., Kumar, S., Pattanayak, A., Kar, A., and Bishi, S. K. (2023) Optimizing raffinose family oligosaccharides content in plants: A tightrope walk. Front Plant Sci 14, 1134754
2. Richards, A. B., Krakowka, S., Dexter, L. B., Schmid, H., Wolterbeek, A. P., Waalkens-Berendsen, D. H., Shigoyuki, A., and Kurimoto, M. (2002) Trehalose: a review of properties, history of use and human tolerance, and results of multiple safety studies. Food Chem Toxicol 40, 871-898
3. Backus, K. M., Boshoff, H. I., Barry, C. S., Boutureira, O., Patel, M. K., D'Hooge, F., Lee, S. S., Via, L. E., Tahlan, K., Barry, C. E., 3rd, and Davis, B. G. (2011) Uptake of unnatural trehalose analogs as a reporter for Mycobacterium tuberculosis. Nat Chem Biol 7, 228-235
4. Murray, A., Kilbride, P., and Gibson, M. I. (2024) Trehalose in cryopreservation. Applications, mechanisms and intracellular delivery opportunities. RSC Med Chem 15, 2980-2995
5. Ohtake, S., and Wang, Y. J. (2011) Trehalose: current use and future applications. J Pharm Sci 100, 2020-2053