Non-Enzymatic Methylglyoxal Formation From glucose Metabolites and Generation of Superoxide Anion Radical During Methylglyoxal-Dependent Cross-Links Reaction

Abstract

The paper explores the formation of a-oxoaldehydes during the interaction of glucose metabolites with hydroxyl or alkoxyl radicals. Hydroxyl radicals were generated under radiolysis of aqueous solutions, and alkoxyl radicals (t-BuO · ) were obtained in the model system tert-butyl hydroperoxide/Fe 2+ . High-performance liquid chromatography revealed that methylglyoxal was one of the organic products resulting from t-BuO · -induced transformations of fructose-1,6-bisphosphate under hypoxic conditions. The interaction of lysine and methylglyoxal one of the main targets of a-oxoaldehydes in proteins was also studied. As chemiluminescence and EPR spectroscopy demonstrated, this reaction generates a methylglyoxal anion radical, a cation-radical of methylglyoxal dialkylamine and a superoxide anion radical. EPR signal of methylglyoxal-derived free radicals was observed in hypoxia, whereas only the trace amounts of these free radicals were recorded in the aerated reaction medium.

Dicarbonyl-Dependent Modification of LDL as a Key Factor of Endothelial Dysfunction and Atherosclerotic Vascular Wall Damage

“…Glyoxal is formed at glyoxylation during autooxidation of glucose and other six-atom carbohydrates, whereas methylglyoxal is synthesized during glycolysis during enzymatic oxidation of glucose from triosophosphates [ 38 , 41 , 42 ]. However, as shown in our studies, methylglyoxal can also be formed nonenzymatically when glucose derivatives are attacked by peroxy free radicals [ 43 ].…”

“…When LDL cooxidation in the presence of glucose in concentrations characteristic for blood levels of patients with type 2 diabetes, there is a sharp increase in the rate of LDL lipid peroxidation, which is accompanied by the formation of superoxide anion radical [ 44 ]. Superoxide radical can also be generated during the Maillard reaction at the interaction of methylglyoxal with the end amino groups of LDL apoprotein B-100 [ 43 ]. Thus, in diabetogenesis, in contrast to atherogenesis, carbonyl stress (accumulation of RCS) develops initially, and oxidative stress has a secondary origin and is induced at later stages by reactive oxygen species (ROS) generated due to the reactions described above.…”

“…Pathways of secondary development of oxidative stress in diabetes associated with increased free-radical mechanism of endotheliocyte membrane damage and development of endothelial dysfunction lipoperoxidation in atherogenesis [ 42 , 44 ]; 2. An alternative pathway of oxidative stress development in diabetes associated with the formation of superoxide anion radical and other ROS during the reaction of amino-containing compounds with methylglyoxal (Maillard reaction) [ 43 ]; 3. Non-enzymatic formation of methylglyoxal when glucose derivatives are attacked by alkoxyl lipid radicals [ 43 ]; 4.…”

“…An alternative pathway of oxidative stress development in diabetes associated with the formation of superoxide anion radical and other ROS during the reaction of amino-containing compounds with methylglyoxal (Maillard reaction) [ 43 ]; 3. Non-enzymatic formation of methylglyoxal when glucose derivatives are attacked by alkoxyl lipid radicals [ 43 ]; 4. Chemical modification of LDL, involving various natural dicarbonyls: MDA, glyoxal, and methylglyoxal [ 11 , 24 , 27 , 38 ]; 5.…”

Elimination kinetics of carbonyl-modified low density lipoproteins from bloodstream

“…при ферментативном окислении триозофосфатов [5] и свободнорадикальном окислении шестиатомных углеводов [6] [12], добавляя биотин-сукцинимид в диметилсульфоксиде (ДМСО) из расчёта 100 мкг/мг белка ЛНП и после инкубации в течение 2 ч при комнатной температуре избавлялись от избытка биотина при помощи гель-фильтрации на колонках с Sephadex G25 fine. Биотинилированные ЛНП модифицировали, инкубируя их с МДА, который получали методом кислотного гидролиза из его полуацеталя 1,1,3,3-тетраэтоксипропана [4,13], либо при инкубации в присутствии глиоксаля или метилглиоксаля [4,7].…”