Formation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose

Abstract

The glycation of proteins by glucose has been linked to the development of diabetic complications and other diseases. Early glycation is thought to involve the reaction of glucose with N-terminal and lysyl side chain amino groups to form Schiff's base and fructosamine adducts. The formation of the alpha-oxoaldehydes, glyoxal, methylglyoxal and 3-deoxyglucosone, in early glycation was investigated. Glucose (50 mM) degraded slowly at pH 7.4 and 37 degrees C to form glyoxal, methylglyoxal and 3-deoxyglucosone throughout a 3-week incubation period. Addition of t-BOC-lysine and human serum albumin increased the rate of formation of alpha-oxoaldehydes - except glyoxal and methylglyoxal concentrations were low with albumin, as expected from the high reactivity of glyoxal and methylglyoxal with arginine residues. The degradation of fructosyl-lysine also formed glyoxal, methylglyoxal and 3-deoxyglucosone. alpha-Oxoaldehyde formation was dependent on the concentration of phosphate buffer and availability of trace metal ions. This suggests that alpha-oxoaldehydes were formed in early glycation from the degradation of glucose and Schiff's base adduct. Since alpha-oxoaldehydes are important precursors of advanced glycation adducts, these adducts may be formed from early and advanced glycation processes. Short periods of hyperglycaemia, as occur in impaired glucose tolerance, may be sufficient to increase the concentrations of alpha-oxoaldehydes in vivo.

Hydrazine compounds inhibit glycation of low-density lipoproteins and prevent the in vitro formation of model foam cells from glycolaldehyde-modified low-density lipoproteins

“…Some AGE, such as N ɛ -carboxymethyl-and N ɛ -carboxyethyl-lysines and pentosidine, accumulate with age on tissue proteins, and at an increased rate in LDL and atherosclerotic lesions from patients with diabetes [16,[18][19][20]. N ɛ -Carboxymethyllysine and N ɛ -carboxyethyllysine are formed on reaction of Lys residues with low-molecular-mass aldehydes (glyoxal/glycolaldehyde and methylglyoxal, respectively) arising from glucose and metabolic pathways [21], providing evidence for a role of such aldehydes in diabetes-induced complications. These aldehydes are present at elevated levels in the plasma of patients with diabetes [22,23].…”

Fasting and Postprandial Glycoxidative and Lipoxidative Stress Are Increased in Women With Type 2 Diabetes

“…There are multiple sources and mechanisms in the formation of AGEs in vivo, involving both oxidative and nonoxidative reactions of reducing carbohydrates and other metabolic intermediates with amino acid residues (28). The AGE precursor 3DG, which is increased in patients with diabetes (29), is formed by nonoxidative modifications of Amadori adducts and from fructose-3-phosphate (30). In line with these observations, we found that 3DG increased more after the carbohydrate-rich meals than after the fat-rich meals.…”

Inhibition of human muscle-specific enolase by methylglyoxal and irreversible formation of advanced glycation end products

“…Alterations in the functions of two glycolytic enzymes, triose phosphate isomerase (TIM) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which control the levels of GAP and DHAP may lead to the accumulation of DHAP ( Figure 1) and cause an increase in cellular MG concentration [18,19]. Lower quantities of MG are formed from the decomposition of Amadori products of the autooxidation of free monosugars, or from the oxidation of acetone as well as from L-threonine via aminoacetone [20][21][22]. The level of cellular AGE depends on the intracellular mechanisms of enzymatic MG detoxification in the glyoxalase or aldose reductase system, as well as on the activity of fructosamine-3-kinase and fructoselysine-3-phosphate hydrolase, the enzymes which releases free hexose from proteins glycated at early steps of the Maillard reaction [23,24].…”