Methylglyoxal

About: Methylglyoxal is a research topic. Over the lifetime, 2844 publications have been published within this topic receiving 102037 citations. The topic is also known as: acetylformaldehyde & pyruvaldehyde.

Properties and Mode of Action of a Bactericidal Compound (= Methylglyoxal) Produced by a Mutant of Escherichia coli

Abstract: A lethal product (BPG) produced by a glycerol kinase mutant of Escherichia coli was purified, and its mode of action on E. coli was studied. At concentrations where BPG strongly inhibits in vivo deoxyribonucleic acid, ribonucleic acid, and protein synthesis, it produces small effects on other functions: slight inhibition of respiration and small changes in intracellular pools of substrates, nucleic acids degradation, and adenosine triphosphate levels. BPG also inhibits in vitro protein synthesis and produces inactivation of bacteriophage T4. The bactericidal product has been identified in another laboratory as methylglyoxal (MG). By comparing BPG and MG, we confirmed this observation and concluded that the activity found in our BPG preparation is due to its MG content. We also observed that MG is able to react with guanosine triphosphate. According to these results, it is interpreted that MG could act directly on macromolecular synthesis by reacting with the guanine residues of nucleic acids and its precursors.

Carbonylation Induces Heterogeneity in Cardiac Ryanodine Receptor Function in Diabetes Mellitus

Abstract: Heart failure and arrhythmias occur at 3 to 5 times higher rates among individuals with diabetes mellitus, compared with age-matched, healthy individuals. Studies attribute these defects in part to alterations in the function of cardiac type 2 ryanodine receptors (RyR2s), the principal Ca2+-release channels on the internal sarcoplasmic reticulum (SR). To date, mechanisms underlying RyR2 dysregulation in diabetes remain poorly defined. A rat model of type 1 diabetes, in combination with echocardiography, in vivo and ex vivo hemodynamic studies, confocal microscopy, Western blotting, mass spectrometry, site-directed mutagenesis, and [3H]ryanodine binding, lipid bilayer, and transfection assays, was used to determine whether post-translational modification by reactive carbonyl species (RCS) represented a contributing cause. After 8 weeks of diabetes, spontaneous Ca2+ release in ventricular myocytes increased ∼5-fold. Evoked Ca2+ release from the SR was nonuniform (dyssynchronous). Total RyR2 protein levels remained unchanged, but the ability to bind the Ca2+-dependent ligand [3H]ryanodine was significantly reduced. Western blotting and mass spectrometry revealed RCS adducts on select basic residues. Mutation of residues to delineate the physiochemical impact of carbonylation yielded channels with enhanced or reduced cytoplasmic Ca2+ responsiveness. The prototype RCS methylglyoxal increased and then decreased the RyR2 open probability. Methylglyoxal also increased spontaneous Ca2+ release and induced Ca2+ waves in healthy myocytes. Treatment of diabetic rats with RCS scavengers normalized spontaneous and evoked Ca2+ release from the SR, reduced carbonylation of RyR2s, and increased binding of [3H]ryanodine to RyR2s. From these data, we conclude that post-translational modification by RCS contributes to the heterogeneity in RyR2 activity that is seen in experimental diabetes.

Influence of in Vitro Simulated Gastroduodenal Digestion on Methylglyoxal Concentration of Manuka (Lectospermum scoparium) Honey

Abstract: Manuka honey (MH) is a functional food that shows in vitro antimicrobial activity and to which wound healing properties, positive effects on oral health, and beneficial properties during the treatment of gastrointestinal infection diseases and upper gastrointestinal dyspepsia are assigned. The antibacterial activity of MH is mainly due to its high concentration of methylglyoxal (MGO), a highly bifunctional alkylating agent that can induce rapid nonenzymatic modifications of proteins. The aim of the present study was to investigate the influence of in vitro simulated gastric and gastroduodenal digestion on MGO content of MH. To this aim commercial MH samples, with different MGO concentrations, were submitted to digestion, and MGO was determined before and after digestion by a validated RP-HPLC-DAD method. Moreover, the role of MGO in causing carbonylation of the digestive proteins and influencing their enzymatic activities was investigated. The results showed that after digestion MGO concentration decreases because it reacts with digestive enzymes by carbonylating their free amino groups. Nevertheless, carbonylation of pepsin and pancreatin does not influence their physiological activity and therefore does not seem to interfere with the digestion process.

Determination of urinary glyoxal and methylglyoxal by high-performance liquid chromatography.

Abstract: Carbonyl stress compounds such as glyoxal and methylglyoxal have been recently attracting much attention because of their possible clinical significance in chronic and age-related diseases. A high-performance liquid chromatographic procedure has been developed for the simultaneous quantitation of glyoxal and methylglyoxal in human urine. The assay is based on the reaction of these compounds with 1,2-diamino-4,5-dimethoxybenzene to form fluorescent adducts, which are separated by reversed-phase high-performance liquid chromatography in a total run time of 45 minutes and quantitated fluorometrically using 2,3-pentanedione as an internal standard. Derivatization is performed for diluted urine (100-120 mOsm/kg H2O) under acidic conditions (pH 4.5) at 60 degrees C over a prolonged time (15 h) to maximize the yields. The assay is specific and sensitive enough to analyze urinary levels of glyoxal and methylglyoxal with the within- and between-day relative standard deviations of less than 5%. Urinary levels (mean +/- standard deviation, n = 16) of glyoxal and methylglyoxal in healthy subjects were 4.7 +/- 1.35 microg/mg creatinine, 2.2 +/- 0.65 microg/mg creatinine, respectively, the former being 2 to 3 times more than the latter in every subject. The glyoxal and methylglyoxal levels positively correlated with each other, which may suggest that the levels reflect the individual activity of glyoxalase by which both compounds are detoxified.