Methylglyoxal-induced modification of myoglobin: An insight into glycation mediated protein aggregation.

Abstract

Post-translational modification of proteins by Maillard reaction, known as glycation, is thought to be the root cause of different complications, particularly in diabetes mellitus and age-related disorders. Methylglyoxal (MG), a reactive α-oxoaldehyde, increases in diabetic condition and reacts with the proteins to form advanced glycation end products (AGEs) following a Maillard-like reaction. In a time-dependent reaction study of MG with the heme protein myoglobin (Mb), MG was found to induce significant structural alterations of the heme protein, such as heme loss, changes in tryptophan fluorescence, and decrease of α-helicity with increased β-sheet content. These changes were found to occur gradually with increasing period of incubation. Incubation of Mb with MG induced the formation of several AGE adducts, including, carboxyethyllysine at Lys-16, carboxymethyllysine at Lys-87, carboxyethyllysine or pyrraline-carboxymethyllysine at Lys-133, carboxyethyllysine at Lys-42 and hydroimidazolone or argpyrimidine at Arg-31 and Arg-139. MG induced amyloid-like aggregation of Mb was detected at a longer period of incubation. MG-derived AGEs, therefore, appear to have an important role as the precursors of protein aggregation, which, in turn, may be associated with pathophysiological complications.