Protein Cross-linking by the Maillard Reaction

Abstract

The Maillard reaction, initiated by the nonenzymatic reaction of reducing sugars with proteins, is proposed to play a significant role in protein aging and the complications of aging and diabetes. The reaction is initiated with the reversible formation of a Schiff base between a reducing sugar and the amino group of a protein. The relatively unstable Schiff base undergoes rearrangement to form a more stable Amadori product. The Amadori product, over a period of several months to years, undergoes a series of further reactions through dicarbonyl intermediates to form advanced glycation end products (AGEs) 1 that are also known as advanced Maillard products. The AGEs are a heterogeneous group of structures formed as both cross-linking and noncross-linking adducts on proteins. The long-lived proteins in the body like lens crystallins and collagen accumulate AGEs because of their negligible or slow turnover. Immunochemical and chemical methods have clearly shown the progressive accumulation of AGEs in tissue proteins in aging (1-3). In diabetes, AGE accumulation in general is accelerated and linked to atherosclerosis, nephropathy, neuropathy, retinopathy, and cataract (4 -8). The binding of AGEs to specific receptors on macrophages has been shown to result in the synthesis of cytokines and growth factors and enhanced oxidative stress (9 -12). These events are proposed to play a major role in age-and diabetes-associated vascular complications.Considerable interest has focused recently on the structural characterization of AGEs. Attempts are being made to isolate major products by using specific antibodies and by chromatographic methods. A consistent difficulty in these procedures has been the isolation of individual AGEs in a reaction where numerous products are formed with highly cross-linked structures. Although protein cross-linking is a major end result of the Maillard reaction, only two minor protein cross-linking compounds, pentosidine and fluorophore LM-1, have been detected in tissues (13)(14)(15). Therefore, to better understand the impact of the Maillard reaction in aging and diabetes and to develop effective therapeutic methods to prevent AGE accumulation in tissues, it is necessary to elucidate the chemical nature of the major protein cross-links derived from this reaction.In addition to glucose, a number of other sugars and sugar metabolites are known to initiate the Maillard reaction. Among them methylglyoxal (MG) has attracted considerable attention recently. MG is formed by enzymatic and nonenzymatic routes from glycolytic intermediates as well as from autoxidation of sugars (16,17). It has been shown that in diabetes the concentration of MG increases in the lens, blood, and kidney (18 -20). In Type I diabetic patients the blood MG levels increased 5-6-fold and in Type II 2-3-fold compared with normal control

Glucose delays seed germination in Arabidopsis thaliana

“…As an aldehyde, glucose is chemically reactive. Biochemical interactions between reducing sugars and proteins, known as the Maillard reaction, lead to the formation of glycoproteins and advanced glycation end products (AGEs: heterogeneous group of structures formed as both cross-linking and non-cross-linking adducts on proteins; Nagaraj et al 1996). The formation of these products is proposed to play an important role in protein aging.…”

Formation Pathways for Lysine-Arginine Cross-links Derived from Hexoses and Pentoses by Maillard Processes

“…So far, pentosidine 11 ( Fig. 1) (15), fluorophore LM-1 (16,17), crossline (18), MOLD (19), and GOLD (20,21) have been detected in vivo. Some of the cross-links (e.g.…”

Generation of Superoxide Anions during the Reaction of Guanidino Compounds with Methylglyoxal.

“…4) Moreover, it was identified as a precursor of AGE [5][6][7] which accumulates in the plasma of uremic patients at a reported concentration of 1.53Ϯ0.25 mM. 8) This compound is known to react with the guanidino group in proteins 4,7,9,10) and it binds and reversibly modifies arginine residues. [11][12][13] The reactions have been shown to occur even at physiological concentrations of methylglyoxal.…”