Arginine-Derived Advanced Glycation End Products Generated in Peptide–Glucose Mixtures During Boiling

Abstract

Glycation refers to the reaction of amino groups, for example in proteins, with reducing sugars. Intermediately formed Amadori products can be degraded by oxidation (Maillard reactions) leading to a heterogeneous class of advanced glycation end-products (AGEs), especially during exposure to heat. AGEs are considered to be toxic in vivo due to their pronounced local and systemic inflammatory effects. At high temperatures, these reactions have been mostly investigated at the amino acid level. Here, we studied the formation of arginine-related AGEs in peptides under conditions simulating household cooking at physiological d-glucose concentrations. High quantities of AGE-modified peptides were produced within 15 min, especially glyoxal-derived products. The intermediately formed dihydroxy-imidazolidine yielded glyoxal- (Glarg) and methylglyoxal-derived hydro-imidazolinones (MG-H), with Glarg being further degraded to carboxymethyl-l-arginine (CMA). Carboxyethyl-l-arginine was not detected. The formation rates and yields were strongly increased in the presence of physiologically relevant concentrations of Fe(II)-ions and ascorbate. A nearby histidine residue increased the content of AGEs, whereas glutamic acid significantly reduced the CMA levels.

Osmotic stress is accompanied by protein glycation inArabidopsis thaliana

“…The pattern of individual AGE classes was dominated by CML, CMA (or isomeric glyoxal-derived dihydroxyimidazolidine, GD-HI (Frolov et al , 2014 b ) and MG-H (Supplementary Fig. S7).…”

“…The most striking differences were observed for the peptides containing the two glyoxal-derived residues: Glarg and its hydrolysis product, CMA. It is important to mention that the increment of 58 m / z can also correspond to GD-HI, known to be the Glarg precursor (Frolov et al , 2014 b ). In contrast, the differences in the modification rates were less pronounced for the methylglyoxal-derived modifications (MG-H and CEA), which was in accordance with higher abundance of glyoxal in leaf tissues (Supplementary Fig.…”

Oxidative degradation of N ε-fructosylamine-substituted peptides in heated aqueous systems

“…comprehensively characterized for amino acids (Glomb and Monnier 1995;Kloepfer et al 2011) and peptides (Frolov et al 2014), AGE formation via degradation of Amadori and Heyns compounds is less understood. However, this aspect has a high relevance in physiology, food chemistry, and nutrition science.…”

Identification of Glucose-Binding Pockets in Human Serum Albumin Using Support Vector Machine and Molecular Dynamics Simulations

“…However, these pockets contain arginine residues (Arg257, Arg445 and Arg485 respectively). Arginine residues have also been reported to undergo glycation [85]. Taken together, our methodology has identified seven new potential glycation sites containing lysine or arginine residues of which two sites are cryptic.…”