Glycation With Fructose: The Bitter Side of Nature's Own Sweetener

Fructose is a ketohexose and sweetest among all the natural sugars. Like other reducing sugars, it reacts readily with the amino- and nucleophilic groups of proteins, nucleic acids and other biomolecules resulting in glycation reactions. The non-enzymatic glycation reactions comprise Schiff base formation, their Amadori rearrangement followed by complex and partly incompletely understood reactions culminating in the formation of Advance Glycation End products (AGEs). The AGEs are implicated in complications associated with diabetes, cardiovascular disorders, Parkinson's disease, etc. Fructose is highly reactive and forms glycation products that differ both in structure and reactivity as compared to those formed from glucose. Nearly all tissues of higher organisms utilize fructose but only a few like the ocular lens, peripheral nerves erythrocytes and testis have polyol pathway active for the synthesis of fructose. Fructose levels rarely exceed those of glucose but, in tissues that operate the polyol pathway, its concentration may rise remarkably during diabetes and related disorders. Diet contributes significantly to the body fructose levels however, availability of technologies for the large scale and inexpensive production of fructose, popularity of high fructose syrups as well as the promotion of vegetarianism have resulted in a remarkable increase in the consumption of fructose. In vivo glycation reactions by fructose, therefore, assume remarkable significance. The review, therefore, aims to highlight the uniqueness of glycation reactions with fructose and its role in some pathophysiological situations.