Showing papers on "Methylglyoxal published in 1995"
TL;DR: Results indicate that dicarbonyl compounds cross-link free amino groups of protein by forming Schiff bases, which donate electrons directly to dicarbon compounds to form the cross-linked radical cations and the methylglyoxal radical anions.
269 citations
TL;DR: Analysis of amino acid modification, gel filtration chromatographic, and electrophoretic characteristics of bovine and human serum albumins irreversibly modified by methylglyoxal and by glucose-derived advanced glycation endproducts suggested that AGE formed from glucose-modified proteins and AGE-like compounds formed from methyl glyoxal- modified proteins may both be signals for recognition and degradation of senescent macromolecules.
Abstract: The amino acid modification, gel filtration chromatographic, and electrophoretic characteristics of bovine and human serum albumins irreversibly modified by methylglyoxal (MG-SA) and by glucose-derived advanced glycation endproducts (AGE-SA) were investigated. Methylglyoxal selectively modified arginine residues at low concentration (1 mM); at high methylglyoxal concentration (100 mM), the extent of arginine modification increased and lysine residues were also modified. Both arginine and lysine residues were modified in AGE-SA. Analytical gel filtration HPLC of serum albumin derivatives suggested that the proportion of dimers and oligomers increased with modification in both low and highly modified MG-SA and AGE-SA derivatives relative to unmodified serum albumins. In SDS-PAGE analysis, dimers and oligomers of low-modified MG-SA were dissociated into monomers, but not in highly modified MG-SA. MG-SA had increased anodic electrophoretic mobility under nondenaturing conditions at pH 8.6, indicating an increased net negative charge, which increased with extent of modification; highly modified MG-SA and AGE-SA had similar high electrophoretic mobilities. MG-SA derivatives were fluorescent: the fluorescence was characteristic of the arginine-derived imidazolone N delta-(5-methyl-4-imidazolon-2-yl)ornithine, but other fluorophores were also present. AGE-SA had similar fluorescence, attributed, in part, to glucose-derived imidazolones. AGE formed from glucose-modified proteins and AGE-like compounds formed from methylglyoxal-modified proteins may both be signals for recognition and degradation of senescent macromolecules.
223 citations
TL;DR: The increased expression of glyoxalase-I may be linked to a higher demand for ATP generation and to enhanced glycolysis in salt-stressed plants.
Abstract: A cDNA, GLX1, encoding glyoxalase-I was isolated by differential screening of salt-induced genes in tomato. Glyoxalases-I and-II are ubiquitous enzymes whose functions are not clearly understood. They may serve to detoxify methylglyoxal produced from triosephosphates in all cells. The protein encoded by GLX1 shared 49.4% and 58.5% identity with glyoxalase-I isolated from bacteria and human, respectively. Furthermore, yeast cells expressing GLX1 showed a glyoxalase-I specific activity 20-fold higher than non-transformed cells. Both GLX1 mRNA and glyoxalase-I polypeptide levels increased 2- to 3-fold in roots, stems and leaves of plants treated with either NaCl, mannitol, or abscisic acid. Immunohistochemical localization indicated that glyoxalase-I was expressed in all cell types, with preferential accumulation in phloem sieve elements. This expression pattern was not appreciably altered by salt-stress. We suggest that the increased expression of glyoxalase-I may be linked to a higher demand for ATP generation and to enhanced glycolysis in salt-stressed plants.
174 citations
TL;DR: In every reaction involving 9-mG, N2-(1-carboxyethyl)-9-methylguanine (CEmG) was a major product which was produced and appears to result from the nucleophilic addition of the primary amino group of guanine to the ketone group of MG followed by an intramolecular rearrangement.
Abstract: Reducing sugars such as glucose react nonenzymatically with protein amino groups to initiate a posttranslational modification process known as advanced glycosylation. Nucleotide bases also participate in advanced glycosylation reactions, producing DNA-linked advanced glycosylation endproducts (AGEs) that cause mutations and DNA transposition. Although several protein-derived AGEs have been isolated and structurally characterized, AGE-modified nucleotides have not yet been reported. We systematically examined the reactivities of the model nucleotide bases 9-methylguanine (9-mG), 9-methyladenine (9-mA), and 1-methylcytosine (1-mC) toward glucose and several glucose-derived reactants. In "fast" reactions performed at refluxing temperature and physiological pH, 1 equiv of nucleotide base was reacted with 10 equiv of D-glucose, D-glucose 6-phosphate (G-6-P), D-glucose 6-phosphate/lysine (G-6-P/Lys), the Schiff base 1-n-propylamino-N-D-glucoside (SB), or the Amadori product 1-n-propylamino-N-D-fructose (AP). In every reaction involving 9-mG, N2-(1-carboxyethyl)-9-methylguanine (CEmG) was a major product which was produced. N2-(1-carboxyethyl)-9-methylguanine also formed from 9-mG and AP in long-term incubations performed at 37 degrees C. Direct treatment of 9-mG with methylglyoxal (MG), a Maillard reaction propagator that forms from the decomposition of AP, also produced CEmG in high yield. N2-(1-Carboxyethyl)-9-methylguanine appears to result from the nucleophilic addition of the primary amino group of guanine to the ketone group of MG followed by an intramolecular rearrangement. Methylglyoxal is a known prokaryotic mutagen and was shown additionally to be mutagenic in a eukaryotic shuttle vector assay system.(ABSTRACT TRUNCATED AT 250 WORDS)
160 citations
TL;DR: The complexity of the regulation of metabolism of methyl glyoxal implies that the glycolytic methylglyoxal pathway is not only a detoxification system in cells, but also may have some significant functions in the characteristic properties of living systems—that is growth, proliferation, and differentiation.
Abstract: Publisher Summary This chapter focuses on the multilateral effects of methylglyoxal and discusses the biological significance and function of methylglyoxal with respect to metabolic pathways, regulation of enzyme activity and expression of the gene in some microorganisms. The production of S-D-lactoylglutathione, an intermediate of the glyoxalase system, and its physiological activity are described. There are insufficient data on the route by which glucose is metabolized to pyruvic acid in mutants, deficient in the enzymes, involved in glycolysis or in the glycolytic methylglyoxal pathway. Oxidative conversion of methylglyoxal to pyruvic acid is also not energy-generating. These routes are not an equivalent to glycolysis with respect to energy conservation. The complexity of the regulation of metabolism of methylglyoxal implies that the glycolytic methylglyoxal pathway is not only a detoxification system in cells, but also may have some significant functions in the characteristic properties of living systems—that is growth, proliferation, and differentiation. The chapter discusses the formation and metabolism of methylglyoxal, genes for metabolic enzymes of methylglyoxal in microorganisms, regulation of glyoxalase I activity in yeast, and S-D-lactoylglutathione.
149 citations
TL;DR: It is demonstrated that mutants lacking the channels can be protected against the lethal effects of methylglyoxal by acidification of the cytoplasm with a weak acid and the implications for pHi‐mediated resistance to methylglyxal are discussed.
Abstract: Escherichia coli possesses two glutathione-gated potassium channels, KefB and KefC, that are activated by glutathione-S-conjugates formed with methylglyoxal. We demonstrate that activation of the channels leads to cytoplasmic acidification and that this protects cells during electrophilic attack. Further, we demonstrate that mutants lacking the channels can be protected against the lethal effects of methylglyoxal by acidification of the cytoplasm with a weak acid. The degree of protection is determined by the absolute value of the pHi and the time at which acidification takes place. Alterations in the pHi do not accelerate the rate of detoxification of methylglyoxal. The mechanism by which methylglyoxal causes cell death and the implications for pHi-mediated resistance to methylglyoxal are discussed.
107 citations
TL;DR: The p-hydroxymercuribenzoate-inactivated enzyme could be almost completely re-activated by dithiothreitol and other thiol-group-containing compounds, indicating the possible involvement of thiol group(s) at or near the active site of the enzyme.
Abstract: A single novel enzyme, glyoxalase III, which catalyses the conversion of methylglyoxal into D-lactate without involvement of GSH, has been detected in and purified from Escherichia coli Of several carbonyl compounds tested, only the alpha-ketoaldehydes methylglyoxal and phenylglyoxal were found to be substrates for this enzyme Glyoxalase III is active over a wide range of pH with no sharp pH optimum In its native form it has an M(r) of 82000 +/- 2000, and it is composed of two subunits of equal M(r) Glutathione analogues, which are inhibitors of glyoxalase I, do not inhibit glyoxalase III Glyoxalase III is found to be sensitive to thiol-blocking reagents The p-hydroxymercuribenzoate-inactivated enzyme could be almost completely re-activated by dithiothreitol and other thiol-group-containing compounds, indicating the possible involvement of thiol group(s) at or near the active site of the enzyme
106 citations
TL;DR: The glyoxalase system in oncology and haematology and genetics, polymorphism and gene cloning, and the interest for oncologists andHaematologists, is summarized.
Abstract: 5. Introduction: the glyoxalase system 1.1. The glyoxalase system in oncology and haematology 1.1.1. The interest for oncologists and haematologists 1.1.2. The glyoxalase system: a definition 1.2. Glyoxalase I 1.2.1. Distribution and molecular characteristics 1.2.2. Physiological substrates, kinetics and mechanism 1.2.3. The active site and catalytic mechanism 1.2.4. Genetics, polymorphism and gene cloning 1.25. Non-giyoxalase I-dependent metabolism of methylglyoxal by aldehyde reductases to lactaldehyde and hydroxyacetone 1.3. Glyoxalase II 1.3.1. Distribution and molecular characteristics 1.3.2. Substrate specificity, kinetics and mechanism 1.3.3. Genetics and polymorphism 1.3.4. D-Lactate metabolism and excretion
104 citations
TL;DR: In this paper, the authors measured the rate of the reaction of CH3CO radicals with methylglyoxal from 260 to 333 K using the discharge flow technique and laser-induced fluorescence detection of OH.
Abstract: Rate coefficients have been measured for the reaction of OH radicals with methylglyoxal from 260 to 333 K using the discharge flow technique and laser-induced fluorescence detection of OH. The rate coefficient was found to be (1.32±0.30) × 10−11 cm3 molecule−1 s−1 at room temperature, with a distinct negative temperature dependence (E/R of −830 ± 300 K). These are the first measurements of the temperature dependence of this reaction. The reaction of OH with acetaldehyde was also investigated, and a rate coefficient of (1.45 ± 0.25) × 10−11 cm3 molecule−1 s−1 was found at room temperature, in accord with recent studies. Experiments in which O2 was added to the flow showed regeneration of OH following the reaction of CH3CO radicals with O2. However, chamber experiments at atmospheric pressure using FTIR detection showed no evidence for OH production. FTIR experiments have also been used to investigate the chemistry of the CH3COCO radical formed by hydrogen abstraction from methylglyoxal. © 1995 John Wiley & Sons, Inc.
64 citations
TL;DR: In this article, the rate and mechanism of methylglyoxal (MGLY, CH3COCHO) photolysis under tropospheric conditions were determined for various wavelength bands between 240 and 480 nm.
Abstract: Laboratory studies have been conducted to determine the rate and mechanism of methylglyoxal (MGLY, CH3COCHO) photolysis under tropospheric conditions. The UV/visible absorption cross sections of MGLY as a function of wavelength have been measured at three different temperatures, 248 K, 273 K, and 298 K. The absorption cross sections show only small variations (≤10%) over this temperature range. The results at 298 K are in agreement with the values published by Meller et al. (1991) and differ by almost a factor of 2 from earlier work published by Plum et al. (1983). The quantum yields and products of the photolysis are reported for various wavelength bands between 240 and 480 nm. The dominant pathway for photolysis at wavelengths relevant to the troposphere produces two radicals, CH3COCHO + hν → CH3CO + HCO. The measured absorption cross sections and quantum yields are used to determine a methylglyoxal lifetime for photolysis of (2.7±0.7) hours, for a solar zenith angle of 0–60°. The kinetics and mechanism for reaction of HO2 with methylglyoxal were also determined. Although this reaction is unimportant for the atmospheric oxidation of methylglyoxal, the results were used in the interpretation of the quantum yield experiments.
56 citations
TL;DR: The 1,3-di Nα-hippuryllysino-4methylimidazolium salt has been identified as a major product of reaction of the α-dicarbonyl compound, methylglyoxal 1, with the lysine derivative, nα-benzoylglycyllysine2, in phosphate buffer at neutral pH, suggesting a mechanism for crosslinking of protein by 1 and related dicaronyl compounds during the Maillard reaction as mentioned in this paper.
Abstract: The 1,3-di-Nα-hippuryllysino-4-methylimidazolium salt 6 has been identified as a major product of reaction of the α-dicarbonyl compound, methylglyoxal 1, with the lysine derivative, Nα-hippuryllysine (Nα-benzoylglycyllysine)2, in phosphate buffer at neutral pH, suggesting a mechanism for crosslinking of protein by 1 and related dicarbonyl compounds during the Maillard reaction.
TL;DR: Transfection of a 622 bp cDNA encoding human glyoxalase I into murine NIH3T3 cells shows a consistent increase in tumour tissue when compared with pair-matched controls, suggesting increased glyoxAlase I is associated with the malignant phenotype and may also contribute to protection against the cytotoxicity of certain anti-cancer drugs.
Abstract: The glyoxalase system (glyoxalase I, glyoxalase II and GSH as cofactor) is involved in the detoxification of methylglyoxal (a byproduct of the glycolytic pathway) and other alpha-oxoaldehydes. We have transfected a 622 bp cDNA encoding human glyoxalase I into murine NIH3T3 cells. The recipient cells were shown to express elevated transcript and protein levels and a 10-fold increase in glyoxalase I enzyme activity. This was accompanied by an increased tolerance for exogenous methylglyoxal and enhanced resistance to the cytotoxic effects of two glyoxalase I inhibitors (s-p-bromobenzylglutathione diethyl ester and s-p-bromobenzylglutathione dicyclopentyl ester), a glutathione analogue [gamma-glutamyl-(S)-(benzyl)cysteinyl-(R)-(-)-phenylglycine diethyl ester] and the anti-cancer drugs mitomycin C and adriamycin. Steady-state levels of GSH were significantly lower in the transfected cells, perhaps reflecting increased flux as a consequence of elevated glyoxalase activity. This decrease did not alter the sensitivity to the alkylating agent chlorambucil. Although transfection did not affect the growth or doubling time of the NIH3T3 cells, analysis of glyoxalase I activity showed a consistent increase in tumour tissue when compared with pair-matched controls. Thus increased glyoxalase I is associated with the malignant phenotype and may also contribute to protection against the cytotoxicity of certain anti-cancer drugs.
TL;DR: Investigation of the reaction of methylglyoxal with isolated human and bovine lens crystallins yielded stable adducts that exhibited fluorescent properties and showed an overall loss of positive charge and an increase in molecular weight and non-disulfide covalent crosslinking.
01 Dec 1995
TL;DR: High speed membrane fractions from rat aorta homogenates metabolized the aliphatic amine aminoacetone to methylglyoxal, and this deaminating activity appears to be due to a semicarbazide-sensitive amine oxidase (SSAO), which is associated with smooth muscle cells in blood vessels of the rat and other species.
TL;DR: MG is capable of inducing hprt mutations as well as DNA adducts in human lymphocytes at doses with low cytotoxicity, and seems to be a comparatively weak mutagen in this system.
Abstract: Methylglyoxal (MG) is a mutagen present in several foodstuffs, including coffee. We have used the 32P-postlabelling method to measure MG-deoxyguanosine adduct levels, and the T-cell cloning technique, to study the frequency of hprt (hypoxanthine-guanine phosphoribosyl transferase) mutant cells after treatment of human lymphocytes with MG in vitro. The mutant induction by single (18 hr) high-dose (1.0-1.5 mM) treatment was comparable to that induced by repeated (3 x 48 hr) low-dose (0.1-0.4 mM) treatment. The latter also correlated with the adduct levels measured in the same experiment. The relative cell survival measured by direct cloning after the final treatment agreed well with the growth curves monitored during the expression phase. Our results show that MG is capable of inducing hprt mutations as well as DNA adducts in human lymphocytes at doses with low cytotoxicity. However, significant adduct formation (two- to threefold) could be obtained only after the first exposure in cells subjected to a repeated treatment protocol, and the induced mutant frequency was low (two- to fourfold over background). Thus, MG seems to be a comparatively weak mutagen in this system.
TL;DR: This work describes enzyme kinetic characterization of a second sulphonylnitromethane, 3',5'-dimethyl-4'-nitromethylsulphonyl-2-(2-tolyl)acetanilide (ZD5522), which is at least 10-fold more potent against bovine lens aldose reductase in vitro and which also has a greater efficacy for reduction of rat nerve sorbitol levels in vivo.
TL;DR: It is observed that rats above 27 months old were decrepit as judged by external appearance movement and other physiological data of them and age-related changes in the levels of D-lactate and its related compounds in rat tissues are reported.
TL;DR: In this paper, the formation of methyl-glyoxal from fructose takes place in a reaction of 1.5 order with an activation energy of 0.5 kJ/mol.
Abstract: Verschieden konzentrierte wasrige Fructose-Losungen (Molenbruch 0,1–1) wurden in Zeitintervallen von 5 bis 80 min bei einer Temperatur von 130 bis 150 °C erhitzt und das sich dabei bildende Methylglyoxal bestimmt. Methylglyoxal bildet mit o-Phenylendiamin das Derivat 3-Methylchinoxalin und zeigt eine Absorption im UV-Bereich. Nach der Separierung und Standardisierung mittels HPLC besteht die Moglichkeit, den Gehalt an Methylglyoxal aus dem Derivat mit einen UV-Detektor zu bestimmen. Nach ersten Ergebnissen war die Menge an Methylglyoxal zu gering, wahrscheinlich ist es an weiteren Reaktionen beteiligt. In der Folge wurde eine Fruktose-Losung mit einem Zusatz an o-Phenylendiamin in einer solchen Menge erhitzt, die ausreicht, um alles Methylglyoxal zu 3-Methylchinoxalin umzusetzen. Wahrend der Untersuchungen wurde die Konzentration an Methylglyoxal unter den Bedingungen der Karamelisierung in warmebehandelter D-Fructose gemessen und die kinetischen Parameter des Prozesses ermittelt. Es wurde festgestellt, das unter diesen Bedingungen die Bildung von Methylglyoxal in erhitzten Fructose-Losungen gemas einer Reaktion 1,5ter Ordnung erfolgt und die Aktivierungsenergie dabei 0,5 kJ/mol betragt.
Concentrated solutions of fructose (0.1 – 1 molfraction) in water were heated at 130 – 150 °C until 5 – 80 min in sealed test-tubes and the formed methyl-glyoxal was determined. Methyl-glyoxal reacts with o-phenylen-diamin, produces 3-methyl-chinoxalin absorbing in the UV range and gives a possibility to determine the methyl-glyoxal by HPLC. The first results show very few methyl-glyoxal since biggest part of them takes part in further reactions, too. If o-phenylen-diamin was given to the fructose solution before the heating process the methyl-glyoxal can react with it in the moment of formation. The methyl-chinoxalin was determined by HPLC and the methyl-glyoxal quantity was calculated. The formation of methyl-glyoxal from fructose takes place in a reaction of 1.5 order with an activation energy of 0.5 kJ/mol.
Journal Article•
TL;DR: The antitumor effect of MGBCP was additively potentiated by combined treatment with MTX, ADM and HIFO, respectively.
Abstract: The antitumor effect of a polyamine biosynthetic pathway inhibitor methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP) on human osteosarcoma cell lines such as KHOS-240S, MG-63 and G-292 cells, and its effect in combination with anticancer drugs such as methotrexate (MTX), adriamycin (ADM) and 4-hydroperoxyfosfamide (HIFO) have been investigated The growth of these cultured osteosarcoma cells was inhibited by MGBCP in a dose-dependent manner Spermidine and spermine levels were dose-dependently depressed in these MGBCP-treated osteosarcoma cells The antitumor effect of MGBCP was additively potentiated by combined treatment with MTX, ADM and HIFO, respectively
TL;DR: Glyoxal should be prior to methylglyoxal as regards the toxicological assessment of ozonation products in drinking water because of less elimination of glyoxal by granular activated carbon-filtration.
Abstract: The occurrence, biodegradation and DNA lesion of glyoxal derivatives as ozonation products, glyoxal and methylglyoxal were compared from the viewpoint of consequences for human health effect. The ozonation of three kinds of humic acids from different origins resulted in the tendency of more formation of glyoxal than methylglyoxal. Methylglyoxal showed high basepair substitution mutagenicity but was easily decomposed by glyoxalase system or S9 mix, compared to glyoxal. In rat hepatocytes, glyoxal induced 2-3 times more apparent frequency of DNA single-strand breaks than methylglyoxal, while only methylglyoxal induced DNA crosslink at about 1/10 frequency of the DNA single-strand breaks. During the process of ozone treatment pilot-scale plant, glyoxal showed 2 times higher formation after ozonation than methylglyoxal, and the concentration after chlorination was higher than that of chlorinated water from the conventional process because of less elimination of glyoxal by granular activated carbon-filtration. Therefore, all the results indicate that glyoxal should be prior to methylglyoxal as regards the toxicological assessment of ozonation products in drinking water.
Journal Article•
TL;DR: The glyoxalase system catalyses the conversion of methylglyoxal (and other 2-ketoaldehydes) to D-lactic acid via the intermediate S-D-lactoylglutathione, and catalytic amount to reduced glutathione.
Abstract: The glyoxalase system catalyses the conversion of methylglyoxal (and other 2-ketoaldehydes) to D-lactic acid via the intermediate S-D-lactoylglutathione. It comprises two enzymes, glyoxalases I and glyoxalases II, and catalytic amount to reduced glutathione. Methylglyoxal inhibits cell growth, while the glyoxalase system by breaking down methylglyoxal may act as a promoter of cell growth. Inhibitors of glyoxalases may serve as possible therapeutic agents against cancer by virtue of their ability to elevate the level of methylglyoxal in the body.