Triosidines: novel Maillard reaction products and cross-links from the reaction of triose sugars with lysine and arginine residues

Abstract

The role of the highly reactive triose sugars glyceraldehyde and glyceraldehyde-3-phosphate in protein cross-linking and other amino acid modifications during the Maillard reaction was investigated. From the incubation of glyceraldehyde with N (alpha)-acetyl-L-lysine and N (alpha)-acetyl-L-arginine, we isolated four new Maillard reaction pyridinium compounds named 'triosidines'. Two of them, 'lys-hydroxy-triosidine' [1-(5-amino-5-carboxypentyl)-3-[(5-amino-5-carboxypentylamino)methyl]-5-hydroxypyridinium] and 'arg-hydroxy-triosidine' [2-(4-amino-4-carboxybutylamino)-8-(5-amino-5-carboxypentyl)-6-hydroxy-3,4-dihydro-pyrido[2,3-d]pyrimidin-8-ium] are fluorescent, UV-active Lys-Lys and Lys-Arg cross-links respectively. Their structures were identified by NMR and MS. In addition, two UV-active lysine adducts, 'trihydroxy-triosidine' [1-(5-amino-5-carboxypentyl)-3,4-dihydroxy-5-(hydroxymethyl)pyridinium] and 'triosidine carbaldehyde' [1-(5-amino-5-carboxypentyl)-3-formylpyridinium] were tentatively identified by MS. All structures involve six sugar-derived carbons as part of the heterocyclic ring. Of the two novel cross-links, only arg-hydroxy-triosidine was formed by glyceraldehyde-3-phosphate, an intermediate metabolite of the glycolytic pathway. Lys-hydroxy-triosidine and arg-hydroxy-triosidine were detected in human and porcine corneas treated with glyceraldehyde. The HPLC-fluorescence identification was confirmed by MS. Triosidines were also formed from dihydroxyacetone, a widely used artificial sun-tanning agent. Triosidines are expected to be useful tools in tissue engineering, where the utilization of highly reactive sugars is needed to stabilize the loose matrix. In addition, they are expected to be present in selected biological conditions, such as on consumption of a high fructose diet, and syndromes associated with high glyceraldehyde excretion, such as Fanconi Syndrome, fructose-1,6-diphosphatase deficiency and tyrosinaemia.

A mechanism of covalent substrate binding in the x-ray structure of subunit K of the Escherichia coli dihydroxyacetone kinase

“…We propose that formation of the hemiaminal is the chemical basis for efficient discrimination between short-chain ketoses and aldoses on one hand and the structurally similar polyalcohols on the other. The former are chemically reactive and potentially toxic, even at low concentrations (31,32). The latter are compatible solutes, which accumulate to high concentrations as osmoprotectants, for instance in yeast (33).…”

2-Ammonio-6-(3-oxidopyridinium-1-yl)hexanoate (OP-lysine) Is a Newly Identified Advanced Glycation End Product in Cataractous and Aged Human Lenses

“…There is no guarantee that the structures, and the relative amounts of products built in vitro, match those of AGEs formed in vivo. In the contrary, model glycation reaction mixtures can contain major glycation products, which do not exist in vivo (5). Another problem is that the first approach refers to an abstract or imaginary value, "total AGEs," whereas it is clear that at least the known AGEs belong to completely different structural classes having little in common.…”

3-Hydroxypyridine Chromophores Are Endogenous Sensitizers of Photooxidative Stress in Human Skin Cells

“…Importantly, AGE-fluorophores of the N-alkyl-3HP type have been isolated in significant amounts from human tissue, such as glycolaldehyde-pyridine from human atherosclerotic lesions (47). Moreover, Lyshydroxytriosidines, another protein cross-link of the N-alkyl-3-HP type was isolated from human cornea collagen exposed to the artificial tanning agent dihydroxyacetone (48) and is therefore expected to form in appreciable amounts in human skin exposed to this compound. The phototoxicity of 3-HP derivatives as described in this study therefore raises the possibility that chemical tanning of human skin places a suspected photosensitizer in direct proximity to sensitive targets and adds to the increasing health concerns associated with the cosmetic use of dihydroxyacetone preparations (61).…”