The “metabolism” of fructosamines is presently the major research interest of the group. Fructosamines form as a result of a spontaneous condensation reaction of glucose with primary amines, followed by an Amadori rearrangement (Fig. 1). Fructosamines slowly convert to advanced glycation endproducts, which are thought to play a role in the development of diabetic complications. Fructosamine-3-kinase (FN3K) phosphorylates intracellular fructosamines, making them unstable and causing them to detach from proteins, with restoration of the amino group in its original state [1-3,8]. A related enzyme (FN3K-related protein), also found in man and other vertebrates, catalyses the phosphorylation of other osamines [5,7], also leading to their detachment from proteins. A major aim of the group is to evaluate the physiological importance of these two enzymes, which could be to prevent some of the toxic effects of hyperglycemia.    

In connection with this, the group identified also an enzymatic pathway allowing E. coli to utilise as energetic substrate both fructoselysine, a degradation product of glycated proteins, and psicoselysine, the C3 epimer of fructoselysine. The bacterial enzymes identified in this way provide interesting tool to analyse fructosamines and psicosamines.

Role of fructosamine-3-kinase in an intracellular deglycation pathway.

Metabolism of fructoselysine and psicoselysine in E. coli.

The metabolism of fructoselysine and psicoselysine involves their transport to the cytoplasm, presumably via the same transporter (FrlA). Fructoselysine is directly phosphorylated by the fructoselysine 6-kinase and fructoselysine 6-phosphate is converted into lysine and glucose 6-phosphate by the deglycase. Psicoselysine is metabolised through the same pathway, after its epimerization to fructoselysine, catalysed by the fructoselysine 3-epimerase.