Role of reactive aldehyde in cardiovascular diseases.

Glycation of collagen: the basis of its central role in the late complications of ageing and diabetes

The chemistry of the key intermediate in the Maillard reaction, the Amadori rearrangements product, is reviewed covering the areas of synthesis, chromatographic analyses, chemical and spectroscopic methods of characterization, reactions, and kinetics. Synthetic strategies involving free and protected sugars are described in detail with specific synthetic procedures. GC- and HPLC-based separations of Amadori products are discussed in relation to the type of columns employed and methods of detection. Applications of infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy for structural elucidation of Amadori products are also reviewed. In addition, mass spectrometry of free, protected, and protein-bound Amadori products under different ionization conditions are presented. The mechanism of acid/base catalyzed thermal degradation reactions of Amadori compounds, as well as their kinetics of formation, are critically evaluated.

Chemistry of Amadori rearrangement products: Analysis, synthesis, kinetics, reactions, and spectroscopic properties

The amino acid modification, gel filtration chromatographic, and electrophoretic characteristics of bovine and human serum albumins irreversibly modified by methylglyoxal (MG-SA) and by glucose-derived advanced glycation endproducts (AGE-SA) were investigated. Methylglyoxal selectively modified arginine residues at low concentration (1 mM); at high methylglyoxal concentration (100 mM), the extent of arginine modification increased and lysine residues were also modified. Both arginine and lysine residues were modified in AGE-SA. Analytical gel filtration HPLC of serum albumin derivatives suggested that the proportion of dimers and oligomers increased with modification in both low and highly modified MG-SA and AGE-SA derivatives relative to unmodified serum albumins. In SDS-PAGE analysis, dimers and oligomers of low-modified MG-SA were dissociated into monomers, but not in highly modified MG-SA. MG-SA had increased anodic electrophoretic mobility under nondenaturing conditions at pH 8.6, indicating an increased net negative charge, which increased with extent of modification; highly modified MG-SA and AGE-SA had similar high electrophoretic mobilities. MG-SA derivatives were fluorescent: the fluorescence was characteristic of the arginine-derived imidazolone N delta-(5-methyl-4-imidazolon-2-yl)ornithine, but other fluorophores were also present. AGE-SA had similar fluorescence, attributed, in part, to glucose-derived imidazolones. AGE formed from glucose-modified proteins and AGE-like compounds formed from methylglyoxal-modified proteins may both be signals for recognition and degradation of senescent macromolecules.

Molecular characteristics of methylglyoxal-modified bovine and human serum albumins. Comparison with glucose-derived advanced glycation endproduct-modified serum albumins.

Site-specific and random fragmentation of Cu,Zn-superoxide dismutase by glycation reaction. Implication of reactive oxygen species.

Autoxidative degradation of Amadori compounds in the presence of copper ion

Glycation of proteins was induced by incubation of high concentrations of d-glucose (1m) and proteins (4 mg/ml) at 40°C for 7 days. The oxidative damage of glycated protein mediated by addition of traces of metal ion in phosphate buffer (1/15m, pH 7.2) under aerated conditions was investigated. Free amino groups (mainly e-NH2 groups of lysine residues) of protein decreased during the glycation of protein but were regenerated in the oxidation of glycated protein induced with metal ion. Also in this process, an α-dicarbonyl compound was generated. Glycated protein was degraded to lower molecular weight fragments in the presence of Cu(II) but not in the absence of Cu(II). Moreover, the histidine residue of protein was selectively degradated in this oxidative process. The oxidative fragmentations of glycated protein were inhibited by EDTA or catalase, but not by urea, DMSO (scavengers of hydroxy radicals) or superoxide dismutase. A possible mechanism of oxidative fragmentation of glycated protein catalyzed by...

https://www.jstage.jst.go.jp/article/bbb1961/55/8/55_8_1993/_pdf

Jun Tsunehiro

Papers

Autoxidative degradation of Amadori compounds in the presence of copper ion

Oxidative Damage of Glycated Protein in the Presence of Transition Metal Ion