Identification of Fructose 3-Phosphate in the Lens of Diabetic Rats

Abstract

Fructose 3-phosphate, a novel monosaccharide phosphate, has been identified in the lens of diabetic rats. This compound, which is not present in normal lenses, is a protein glycosylating agent and enzyme inactivator. In addition, because of its structural features, this metabolite is relatively labile and undergoes hydrolysis to yield inorganic phosphate and the potent glycosylating agent, 3-deoxyglucosone. The increase in the concentration of fructose 3-phosphate in the lens of diabetic rats suggests that it and its hydrolysis product, 3-deoxyglucosone, may be responsible in part for the development of some diabetic complications in the lens.

Bacterial enzymes that can deglycate glucose- and fructose-modified lysine

“…A second group of deglycating enzymes was discovered by Van Schaftingen and co-workers [7] based on earlier NMR studies by Szwergold et al [8], who reported the existence of fructose 3-phosphate in the lens and an enzyme that can phosphorylate the Amadori product of glucose-modified protein into fructosamine 3-phosphate [9]. Van Schaftingen and co-workers [7] cloned and fully characterized the enzyme, and reported that it had deglycating activity, resulting in 3-deoxyglucosone formation while regenerating the free lysine residue.…”

Aging: Drugs to Eliminate Methylglyoxal, a Reactive Glucose Metabolite, and Advanced Glycation Endproducts

“…Amadori adducts, formed in the intermediate stages of AGEs formation can either be quenched by compounds such as aminoguanidine, or degraded enzymatically by enzymes such as amadoriase and human fructosamine-3-kinase, which belong to this group [149,150]. Amadoriases have not been detected in higher organisms [151,152].…”

“…These enzymes, known as amadoriases, include fructosylamine oxidases [197,198], fructosamine-3-kinase [149,150], fructoselysine-6-kinase [199], fructoselysine-3-epimerase (FrlC) [200], and glucoselysine-6-www.intechopen.com Pharmacology 694 phosphate deglycase [201]. The use of these enzymes or development of stable analogues for deglycation therapy remains speculative .…”

Conversion of a synthetic fructosamine into its 3-phospho derivative in human erythrocytes

“…These peaks, which split into doublets in "H-coupled spectra, correspond to the three most important conformations of fructose 3-phosphate, i.e. (in order of decreasing abundance and from left to right in the spectrum) β-fructopyranose, β-fructofuranose and α-fructofuranose [2,24]. Incubation with DMF also caused the appearance of three peaks, which, as in the case of fructose 3-phosphate, split into doublets in "H-coupled spectra.…”

“…Fructose 3-phosphate is a phosphate ester of unknown function that was first identified by NMR spectroscopy in the lenses of diabetic animals [1,2], and subsequently in human erythrocytes from both control and diabetic subjects [3]. Its formation, to concentrations reaching the millimolar range, can be induced by incubating erythrocytes [4] or lenses [5,6] with fructose.…”