William L. Dills

Protein fructosylation: fructose and the Maillard reaction.

Fructose, as is the case for other reducing sugars, undergoes the Maillard reaction with proteins and amino acids. The first stage of the reaction results in one or more substituted amino sugars. These products in turn enter the advanced and final stages of the Maillard reaction, which involve the formation of reactive intermediates, cross-linking of proteins, and the formation of brown and fluorescent polymeric materials. It would appear that the initial stages of the reaction occur more rapidly with fructose than with glucose. The Maillard reaction with any sugar, including fructose, results in a decrease in protein quality due to the loss of amino acid residues and decreased protein digestibility. Maillard products can inhibit the uptake and metabolism of free amino acids and of other nutrients such as zinc and some advanced Maillard products have mutagenic and/or anticarcinogenic properties. In vivo the Maillard reactions between proteins and fructose, glucose, and other reducing sugars may play a role in aging and in some of the clinical complications of diabetes.

Inhibition of glycogenolysis by 2,5‐anhydro‐D‐mannitol in isolated rat hepatocytes

2,5‐Anhydro‐D‐mannitol, an analog of D‐fructofuranose, inhibited basal and glucagon‐stimulated glycogenolysis and glucose production in hepatocytes isolated from fed rats. Glucose formation from galactose was unaffected by the inhibitor. 2,5‐Anhydro‐D‐mannitol‐1‐phosphate inhibits phosphorylase a with a K i value of 2.4mM. This same phosphorylated metabolite accumulates to the extent of 9.2 μmol/g wet wt in treated hepatocytes suggesting that phosphorolysis is the locus of the inhibition of glucose production from glycogen. Our results suggest that 2,5‐anhydro‐D‐mannitol can be used to produce a model of hereditary fructose intolerance and that it merits further study as a hypoglycemic agent.