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Showing papers on "Methylglyoxal published in 1986"


Journal ArticleDOI
TL;DR: A cup of coffee contains mutagens which produce about 5 X 10(4)-10(5) revertants of Salmonella typhimurium TA 100 without S9 mix, and one of them was identified to be methylglyoxal, which induced tumors in rats when administered by subcutaneous injection.
Abstract: A cup of coffee contains mutagens which produce about 5 X 10(4)-10(5) revertants of Salmonella typhimurium TA 100 without S9 mix. One of the mutagens was identified to be methylglyoxal. Methylglyoxal was present in various beverages such as black tea, whisky, and brandy. Methylglyoxal itself induced tumors in rats when administered by subcutaneous injection. However, the mutagenic properties of coffee were different from those of methylglyoxal. The mutagenicity of coffee was suppressed by catalase, and coffee was found to contain hydrogen peroxide. Furthermore, coffee solution was found to have a hydrogen peroxide-generating system. Instant coffee (15 mg/mL) contains 130 microM hydrogen peroxide immediately after the dissolution of coffee powder in water at room temperature. The concentration of hydrogen peroxide increased with time. The mutagenicity of methylglyoxal was increased by the copresence of hydrogen peroxide. A maximum of 30-fold enhancement was observed. The mutagenicity of black tea but not that of whisky was suppressed by catalase.

119 citations


Journal ArticleDOI
TL;DR: The first structural study of the lowest triplet states of three α-dicarbonyls (glyoxal, methyl glyoxal and biacetyl) using the technique of laser-induced phosphorescence (LIP) spectroscopy in supersonic jets was performed in this article.
Abstract: We report the first structural study of the lowest triplet states of three α‐dicarbonyls (glyoxal, methylglyoxal, and biacetyl) using the technique of laser‐induced phosphorescence (LIP) spectroscopy in supersonic jets. At the level of vibrational resolution, 3Au glyoxal appears to have a geometry very similar to that of the ground state. But the T1←S0 transitions of methylglyoxal and biacetyl each exhibit strong progressions in the torsional vibrations of the methyl groups, showing that these molecules undergo a conformational change on excitation to the lowest triplet state. A Franck–Condon analysis of the methylglyoxal spectrum, with proper consideration for nuclear spin statistics, yields a methyl barrier of V3=115±5 cm−1 in this state. This value has been confirmed by a direct measurement of the tunneling splitting of A and E torsional levels. The hindering potential in the lowest triplet state of methylglyoxal is substantially different from those in the ground (V3=269 cm−1) and first excited single...

78 citations



Journal ArticleDOI
TL;DR: S-hydroxymethylglutathione, formed by pre-equilibrium addition of formaldehyde to glutathione), is concluded to be direct substrate for the dehydrogenase, following the observation that the catalytic turnover number of the enzyme in the forward direction exceeds by a factor of approximately 20 the first order rate constant for decomposition of S-hydruvylglUTathione to glutATHione and formaldehyde.

41 citations


Journal ArticleDOI
TL;DR: In this paper, the NMR spectra of the ether extract of reaction mixtures indicated that methyl glyoxal dialkylimme was produced mainly at an early stage of the reaction of glucose with alkylamine, and was assumed to change to methylglyoxal on the TLC.
Abstract: Formation of a product easily converted to methylglyoxal on TLC with silica gel was observed in an early stage of the reaction mixture of sugar with an alkylamine or amino acid. NMR spectra of the ether extract of reaction mixtures indicated that methylglyoxal dialkylimme was produced mainly at an early stage of the reaction of glucose with alkylamine, and was assumed to change to methylglyoxal on the TLC. The C3 imine production in the t-butylamine system was apparently little and slow compared to that in the normal alkylamine system. A large, rapid production of C3 imine was also observed in the system of the Amadori product and n-butylamine. These results suggested that the C3 formation in the system with normal alkylamine may occur mainly via a newly proposed mechanism, though the ?-butylamine system may possibly produce it according to the scheme proposed by Hodge.

32 citations


Journal ArticleDOI
TL;DR: The result indicated the possible role of glycolytic bypath as a detoxification system of methylglyoxal formed from L-threonine catabolism.
Abstract: L-Threonine catabolism by Saccharomyces cerevisiae was studied to determine the role of glycolytic bypath as a detoxyfication system of 2-oxoaldehyde (methylglyoxal) formed from L-threonine catabolism. During the growth on L-threonine as a sole source of nitrogen, a large amount of aminoacetone was accumulated in the culture. The enzymatic analyses indicated that L-threonine was converted into either acetaldehyde and glycine by threonine aldolase or 2-aminoacetoacetate by NAD-dependent threonine dehydrogenase. Glycine formed was condensed with acetyl-CoA by aminoacetone synthase to form 2-aminoacetoacetate, a labile compound spontaneously decarboxylated into aminoacetone. The enzyme activities of the glycolytic bypath of the cells grown on L-threonine were considerably higher than those of the cells grown on ammonium sulfate as a nitrogen source. The result indicated the possible role of glycolytic bypath as a detoxification system of methylglyoxal formed from L-threonine catabolism.

32 citations


Journal Article
TL;DR: Methylglyoxal was found to induce mutations in Salmonella typhimurium strains TA100, TA102 and TA104, gene conversion in Saccharomyces cerevisiae strain D7, and diphtheria toxin resistance mutation in Chinese hamster lung cells.
Abstract: Methylglyoxal was found to induce mutations in Salmonella typhimurium strains TA100, TA102 and TA104, gene conversion in Saccharomyces cerevisiae strain D7, and diphtheria toxin resistance mutation in Chinese hamster lung cells. Methylglyoxal was detected in coffee, whiskey, a soft drink, toasted bread and soy sauce. The mutagenicity of methylglyoxal was suppressed by sulfite, cysteine, glutathione and dithiothreitol, and enhanced by hydrogen peroxide. Methylglyoxal induced sarcomas in rats at the site of its subcutaneous injection.

27 citations


Journal ArticleDOI
TL;DR: Among the metal ions tested, Zn++ specifically and completely inhibited the activity of the enzyme at a millimolar level and the properties of bacterial glyoxalase I were quite different from mammalian and yeast enzymes.

23 citations


Journal ArticleDOI
TL;DR: EMGBG sulfate was synthesized and was shown to be an extremely powerful competitive inhibitor of eukaryotic S-adenosyimethionine decarboxylase, with an apparent Ki value 12 nᴍ, appearing to be the most powerful known inhibitor of the enzyme.
Abstract: Ethylmethylglyoxal bis(guanylhydrazone) (EMGBG) sulfate, an analog of the well-known anti-leukemic drug methylglyoxal bis(guanylhydrazone), was synthesized. It was shown to be an extremely powerful competitive inhibitor of eukaryotic S-adenosylmethionine decarboxylase, with an apparent Ki value 12 nM. Thus, it appears to be the most powerful known inhibitor of the enzyme, being almost an order of magnitude more powerful than the corresponding ethylglyoxal derivative. It neither inhibited the proliferation of mouse L1210 leukemia cells in vitro, nor did it potentiate the growth inhibition produced by alpha-difluoromethyl ornithine. In this respect, its properties are closely related to those of dimethylglyoxal, ethylglyoxal and propylglyoxal bis(guanylhydrazones), while in striking contrast to those of the antiproliferative glyoxal and methylglyoxal analogs. EMGBG also inhibited intestinal diamine oxidase activity (Ki 0.7 microM). EMGBG sulfate was crystallized from water, giving orthorhombic crystals (space group Pbcn). Their crystal and molecular structure was determined by X-ray diffraction methods. The carbon-nitrogen double bonds between the ethylmethylglyoxal part and the aminoguanidine moieties were found to have the same configuration as they are known to have in the salts of glyoxal, methylglyoxal and propylglyoxal bis(guanylhydrazones). The glyoxal bis(guanylhydrazone) chain of the EMGBG cation deviated strongly from planarity, thus differing dramatically from the corresponding chains of the glyoxal, methylglyoxal and propylglyoxal analogs.

20 citations


Journal ArticleDOI
TL;DR: Hemimercaptal, a non-enzymatic condensation product of methylglyoxal and glutathione, strongly inhibited the activity of the enzyme, and glyoxalase II was purified approximately 100 fold from a cell extract with a 20% activity yield.
Abstract: Glyoxalase II, that catalyzes the conversion of S-lactoylglutathione into lactate and glutathione, was isolated from the yeast, Saccharomyces cerevisiae, and some properties of the enzyme were determined. The glyoxalase II was purified approximately 100 fold from a cell extract with a 20% activity yield. Estimation of the molecular weight of the enzyme by both gel filtration and SDS/polyacrylamide gel electrophoresis gave a value of 1.9 × 104. Among the various thiol esters tested, the enzyme hydrolyzed only S-lactoylglutathione with a Km = 7.0 × 10-6 m . The enzyme was most active at low pH (pH 3 ~4) and was stable even in 0.001 n HCl at 40°C for at least 15 min. The activity of the enzyme was inhibited by various thiol compounds such as glutathione and coenzyme A. Hemimercaptal, a non-enzymatic condensation product of methylglyoxal and glutathione, strongly inhibited the activity of the enzyme.

20 citations


Journal ArticleDOI
TL;DR: Low intracellular S -lactoylglutathione concentration was postulated to account for the observed growth arrest of Saccharomyces cerevisiae cells with hybrid plasmid pYMG14 carrying a gene for NADPH-dependent methylglyoxal reductase of the yeast.

Journal ArticleDOI
TL;DR: α-Dicarbonyl and α-hydroxycarbonyl compounds such as 2,3-butanedione, glyoxal, methylglyoxal , dihydroxyacetone, glyceraldehyde, and glycolaldehyde polymerized both lyso enzyme and acetylated lysozyme, and impaired their Arg residues, however, the elution patterns of the impaired amino acid residues on amino acid analysis were different from that observed with glucose.
Abstract: We studied the mechanism of polymerization of proteins induced by storage with reducing sugars. Glucose alone did not polymerize acetylated lysozyme as a solid (75% relative humidity), but it did when there was free Lys. This indicated that a certain substance generated through a reaction between glucose and amino groups of proteins polymerized the proteins. The substance impaired Arg residues. The impaired Arg residues appeared in three peaks eluting just behind the Phe peak on amino acid analysis.α-Dicarbonyl and α-hydroxycarbonyl compounds such as 2,3-butanedione, glyoxal, methylglyoxal, dihydroxyacetone, glyceraldehyde, and glycolaldehyde polymerized both lysozyme and acetylated lysozyme, and impaired their Arg residues. However, the elution patterns of the impaired amino acid residues on amino acid analysis were different from that observed with glucose.Glyoxal, methylglyoxal, and 2,3-butanedione polymerized proteins to a notable extent even under the conditions used conventionally for chemical modif...

Journal ArticleDOI
TL;DR: Whiletrp-GO-1 polymerized itself very little, Trp-MG-1 did produce some polymers, which suggests that Tr p- MG-1 and trp-3DG-1 may participate in the crosslinking of proteins.
Abstract: To find the mechanism of the amino-carbonyl reaction of proteins with reducing sugars, we examined the reactivity of Nα-acetyl-tryptophan (N-Ac-Trp), a model of tryptophan residues, with various sorts of carbonyl compounds, formaldehyde, acetaldehyde, glyoxal, methylglyoxal, butanedione, and acetone, on incubation at pH 6.8 and 50°C. Aldehydes reacted with N-Ac-Trp, but ketones did not.The most abundant reaction product between N-Ac-Trp and glyoxal (Trp-GO-1) was identified as Nα-acetyl-1-(2-hydroxy-1-oxoethyl)-l-tryptophan and that between N-Ac-Trp and methylglyoxal (Trp-MG-1) was identified as Nα-acetyl-l-(l-hydroxy-2-oxopropyl)-l-tryptophan. From the UV spectrum, a major reaction product between N-Ac-Trp and 3-deoxyglucosone (Trp-3DG-1) was supposed to be analogous to Trp-MG-1.While Trp-GO-1 polymerized itself very little, Trp-MG-1 did produce some polymers. This suggests that Trp-MG-1 and Trp-3DG-1 may participate in the crosslinking of proteins.

Journal ArticleDOI
TL;DR: MGBB showed less SAMDC-stabilizing effect in rat liver in vivo than did methylglyoxal bis-(guanylhydrazone) (MGBG), andethionine incorporation into trichloroacetic acid-insoluble fraction was decreased in the inhibitor-treated cells.

Journal ArticleDOI
TL;DR: The acetone metabolism curves tend to indicate that the capacity for acetone disposal may be enhanced in the 48 hr-fasted pregnant rat, thus enabling the animal to re-use acetone metabolically, possibly for accelerated gluconeogenesis.
Abstract: The administration of a single dose of acetone (100 mg/kg bw) to virgin and 21-day pregnant rats resulted in the appearance of relatively high concentrations of 1,2-propanediol, acetol and methylglyoxal in plasma and liver. In the fetuses no methylglyoxal was detectable. The acetone metabolism curves tend to indicate that the capacity for acetone disposal may be enhanced in the 48 hr-fasted pregnant rat, thus enabling the animal to re-use acetone metabolically, possibly for accelerated gluconeogenesis.

Journal ArticleDOI
TL;DR: The activities of ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SAT) were increased by the addition of methylglyoxal bis(guanylhydrazone) (MGBG) in cultured human erythroid leukemia K 562 cells and were blocked by treatment with cycloheximide, suggesting that the increase of enzyme activity resulted from the synthesis of new enzyme proteins.

Journal ArticleDOI
TL;DR: The present observations may suggest that the initial proliferation of the tumor cells is accompanied with a decrease of MG and further development of the tumors results in an inductive increase of MG level due to the acceleration of sugar catabolism and/or to the decrease of glyoxalase I and II activities.
Abstract: Changes of methylglyoxal (MG) level accompanying the changes of glyoxalase I and II activities were examined in the liver and blood of mice inoculated with L1210 leukemia or Sarcoma 180 intraperitoneally. The amounts of MG in the liver and blood decreased for the first 3-5d after the inoculation of L1210 leukemia or Sarcoma 180 and then increased significantly. Glyoxalase I and II activities, on the other hand, increased for the first 3-5d and then decreased on day 8. The levels of dihydroxyacetone phosphate, glyceraldehyde-3-phosphate and fructose-1, 6-diphosphate decreased gradually during the experimental period of 8d in the liver and blood of mice with Sarcoma 180.The present observations may suggest that the initial proliferation of the tumor cells is accompanied with a decrease of MG and further development of the tumor cells results in an inductive increase of MG level due to the acceleration of sugar catabolism and/or to the decrease of glyoxalase I and II activities.

Journal Article
TL;DR: The aldehyde administration to the purified microtubular protein induces alterations in some tubulin properties already at lower concentrations, which show a possible tubulin-methylglyoxal interaction, also if the reaction mechanism is so far unclear.
Abstract: Methylglyoxal antiproliferative action is well known; this action may be exerted by a non-enzymic mechanism and may directly involve the microtubular system. Our purpose was to verify this hypothesis, by studying the aldehyde effect on normal and tumour microtubular protein. Methylglyoxal incubation of normal and tumour liver cell homogenates causes inhibition of colchicine binding activity above all at higher concentrations. The aldehyde administration to the purified microtubular protein induces alterations in some tubulin properties already at lower concentrations. These results show a possible tubulin-methylglyoxal interaction, also if the reaction mechanism is so far unclear.


Journal ArticleDOI
TL;DR: Two phenylated compounds of methylglyoxal bis(guanylhydrazone), potentially inhibitors of diamine oxidase activity, have been synthesized and their inhibitory capacity was tested; the inhibition of PGBG was non-competitive and the Ki calculated by a Dixon plot was estimated as 1.7 microM.


Journal ArticleDOI
TL;DR: In this article, the reaction of 1,2-hydroxyamino oximes with a hydroxyamino group attached to a tertiary carbon atom with phenyl- and methylglyoxal was described.
Abstract: 2-Acyl-4-hydroxy-2-imidazoline 3-oxide derivatives were obtained by the reaction of 1,2-hydroxyamino oximes with a hydroxyamino group attached to a tertiary carbon atom with phenyl- and methylglyoxal.