Sweet complexity: Sugars and diabetes

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  • Published: Jan 7, 2013
  • Author: David Bradley
  • Channels: NMR Knowledge Base
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Dicarbonyl didact

Phosphate-Catalyzed Degradation of d-Glucosone in Aqueous Solution Is Accompanied by C1-C2 Transposition

NMR spectroscopy has been used to investigate dicarbonyl sugars formed inside the human body from the natural breakdown of the simple sugar, glucose. The implications for understanding the link with diabetes are discussed.

Biochemist Anthony Serianni and postdoctoral research associate, Wenhui Zhang,of the University of Notre Dame in Indiana, USA, are providing important new clues as to the nature of diabetes that one day might lead to novel treatments. Serianni explains that the biological compounds known as dicarbonyl sugars are produced inside the human body from the natural breakdown of the basic sugar compound, glucose. The formation of these sugars occurs to a greater extent in people with diabetes because glucose concentrations in the blood and plasma can be much higher than normal.

"We investigated, under laboratory conditions that approximate those in the body, the degradation of a specific dicarbonyl sugar called glucosone," Serianni explains. The researchers used carbon-13 and proton NMR spectroscopy with labelled compounds, "To establish with certainty the chemical fates of the individual carbons of the glucosone molecule during degradation." Serianni explains further that, "We learned that glucosone degrades by an unanticipated reaction pathway that involves a novel rearrangement of the carbon backbone of the molecule, a process we call C1-C2 transposition."

Hypothetical intrigue

Intriguingly, this finding challenges several aspects of the existing hypothesis regarding how sugar molecules undergo general degradation in the body.

The degradation of sugars is an important process in the body with various physiologically relevant implications. For instance, degraded sugars can interfere with protein structures as we age. They can also lead to the generation of highly reactive by-products of C-C bond fragmentation of Amadori products that can damage components of the cell. Understanding how these molecules are transformed in the body is also essential to understanding the spontaneous cellular processes that take place but that are not necessarily subject to normal cellular controls, Serianni adds. The team has also uncovered yet another role in biochemistry for the phosphate group. The researchers suggest that it can act as a catalyst for sugar degradation, which could have previously unrecognised implications for laboratory and clinical studies.

The current work builds on studies by the Serianni group dating back more than three decades. The study represents the culmination of work on saccharide degradation and rearrangement dating back to 1982, for instance. In that work, the team discovered the first stereospecific C1-C2 transposition reaction of saccharides, catalyzed by molybdate ion, which resulted in a process called C2 epimerization. That early discovery (J Am Chem Soc, 1982, 104, 6764-6769) led to a new and more convenient way to add the requisite carbon-13 label to specific centres in saccharide molecules and has since been commercialised.

Glucosone and diabetes

The team of Serianni and Wenhui Zhang describes details of the glucosone research, which was supported by the National Institute of Diabetes and Digestive and Kidney Disease, in a paper published in the Journal of the American Chemical Society." The primary motivation for conducting this work was mechanistic, namely, to examine the effect of C3 structure on the degradation of 1,2-dicarbonyl sugars; the unusual backbone rearrangement that occurred was unanticipated," the team says.

The findings thus have double-edged implications for human health and diabetes in particular. First regarding the interaction of the compound studied and its effects on proteins and secondly its generation of potentially harmful formate, glycolate, and possibly glyceraldehydes. The team concludes that while, "Some of these by-products are probably harmless when generated sporadically, long-term chronic exposure to them in the diabetic condition may lead to metabolic aberrations not fully appreciated at the present time."

"Wenhui and I have two papers in preparation dealing with the degradation of glucose in phosphate buffer, and on the reaction of molybdate ion with glucosone," Serianni told SpectroscopyNOW. "Turns out, in the latter case, C1-C2 transposition occurs, this time giving two epimeric aldonates." He adds that they are now working out the mechanistic details to explain the observed stereochemistry. In the longer term, Serianni hopes to pursue studies of saccharide degradation mechanisms in more detail using isotopes, especially for reactions involving proteins. "We have great tools now and can look at these complex reactions in much greater depth than has been possible previously," he told us. "I think we are going to be surprised by the myriad ways these multifunctional molecules behave in solution."

Related Links

J Am Chem Soc, 2012, 134, 11511-11524: "Phosphate-Catalyzed Degradation of d-Glucosone in Aqueous Solution Is Accompanied by C1-C2 Transposition"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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