Showing papers on "Methylglyoxal published in 1983"
TL;DR: A mutant strain, fully defective in glyoxalase I and bearing only one nuclear mutation, was obtained and the strain, which is killed by exposure to glycerol, excretes methylglyoxal into the medium.
62 citations
TL;DR: An enzyme from goat plasma which catalyzes the oxidation of aminoacetone to methylglyoxal has been isolated and purified to apparent homogeneity and has been found to be identical with the well known amine oxidase.
46 citations
TL;DR: All of the S-adenosylmethionine decarboxylases were strongly competitively inhibited by methylglyoxal bis(guanylhydrazone) and even more powerfully by its ethyl analogue, although the putrescine-activated enzymes from prostate and yeast were more sensitive than the bacterial and slime-mould enzymes.
Abstract: S-Adenosyl-L-methionine decarboxylases were purified from rat ventral prostate, yeast (Saccharomyces cerevisiae), slime mould (Physarum polycephalum) and bacteria (Escherichia coli) and tested for inhibition by a variety of nucleosides related to S-adenosylmethionine and by methyl- and ethyl-glyoxal bis(guanylhydrazone). Although the enzymes from these different sources are markedly different with respect to activation by cations, the inhibition by nucleosides was quite similar. Very little inhibition was seen when analogues of S-adenosylmethionine with a different base were tested or when the ribose ring was opened or the positive charge on the sulphur atom was not present. Some derivatives in which the amino acid portion of the molecule was altered were more potent inhibitors, but again there was little difference between the enzymes from different sources. 5'-(Dimethylsulphonio)-5'-deoxyadenosine and S-adenosyl-3-methylthiopropylamine were the most inhibitory substances and had similar Ki values, suggesting that the aminopropyl group does not contribute significantly to the binding. All of the S-adenosylmethionine decarboxylases were strongly competitively inhibited by methylglyoxal bis(guanylhydrazone) and even more powerfully by its ethyl analogue, although the putrescine-activated enzymes from prostate and yeast were more sensitive than the bacterial and slime-mould enzymes. All of the S-adenosylmethionine decarboxylases tested bound to a column of methylglyoxal bis(guanylhydrazone) linked to Sepharose and were not eluted by 0.5 M-NaCl, but could be released by 1 mM concentrations of the drug, providing a rapid and efficient method for their purification.
40 citations
TL;DR: Glyoxalase I catalyzes the formation of S-D-lactoyl-glutathione via the hemimercaptal adduct of methylglyoxal and glutathione and this enzymatic reaction was found to be reversible under such conditions that glutathion liberated from the thiolester was trapped.
33 citations
TL;DR: Results demonstrate that the polyamines, especially spermidine and spermine, enhance hyperthermia-induced cell killing by some mechanism involving the plasma membrane, and suggest that methylglyoxal bis-(guanylhydrazone) can act to affect thermal responses by a mechanism other than modification of intracellular polyamine levels.
Abstract: The issue of how polyamines act to sensitize cultured cells to the lethal effects of hyperthermia was investigated using Chinese hamster cells which were induced to express thermotolerance. Intracellular levels of these naturally occurring polycations were manipulated in certain situations by treating whole cells with methylglyoxal bis-(guanylhydrazone), an inhibitor of the S-adenosyl-L-methionine decarboxylases. Exogenous spermine as low as 100 ..mu..M in the culture media dramatically sensitized cells expressing thermotolerance to the lethal effects of subsequent 42/sup 0/C exposures. When thermotolerance was differentially induced in cultures exposed to 42.4/sup 0/C by varying the rate of heating from 37 to 42.4/sup 0/C, the most resistant cells and the highest levels of intracellular spermidine and spermine. This finding was explainable in part by the observation that the putrescine-dependent S-adenosyl-L-methionine decarboxylase activity was minimally affected in cells expressng the greatest degree of thermotolerance. When this enzyme activity was inhibited by drug, lowered intracellular polyamine levels did not correspond with subsequent survival responses to heat. Interestingly, cultures treated with methylglyoxal bis-(guanylhydrazone) 24 hr previous to heat exposure showed a reduced capacity to express rate of heating-induced thermotolerance. Together, these results demonstrate that the polyamines, especially spermidine and spermine, enhance hyperthermia-induced cell killing by some mechanismmore » involving the plasma membrane. Further, our data suggest that methylglyoxal bis-(guanylhydrazone) can act to affect thermal responses by a mechanism(s) other than modification of intracellular polyamine levels.« less
24 citations
TL;DR: Experiments indicated that the methylglyoxal bis(guanylhydrazone)-induced reversal of polyamine depletion was mediated by the known inhibition of diamine oxidase by the diguanidine, and the combination of these two drugs produced a growth-inhibitory effect not achievable with either of the compounds alone.
Abstract: Treatment of mice bearing L1210 leukaemia with 2-difluoromethylornithine, a specific inhibitor of ornithine decarboxylase (EC 4.1.1.17), produced a profound depletion of putrescine and spermidine in the tumour cells. Sequential combination of methylglyoxal bis(guanylhydrazone), an inhibitor of adenosylmethionine decarboxylase (EC 4.1.1.50), with difluoromethylornithine largely reversed the polyamine depletion and led to a marked accumulation of cadaverine in the tumour cells. Experiments carried out with the combination of difluoromethylornithine and aminoguanidine, a potent inhibitor of diamine oxidase (EC 1.4.3.6), indicated that the methylglyoxal bis(guanylhydrazone)-induced reversal of polyamine depletion was mediated by the known inhibition of diamine oxidase by the diguanidine. In spite of the normalization of the tumour cell polyamine pattern upon administration of methylglyoxal bis(guanylhydrazone) to difluoromethylornithine-treated animals, the combination of these two drugs produced a growth-inhibitory effect not achievable with either of the compounds alone.
23 citations
Journal Article•
21 citations
TL;DR: Results provide the first evidence concerning the molecular binding mode of GSH to an enzyme, and arginyl residues are proposed as anionic recognition sites for glutathione on other GSH-utilizing enzymes.
20 citations
TL;DR: A strain which synthesizes a mutant cAMP receptor protein in an adenylate cyclase deletion background is characterized, and it is suggested that growth inhibition in strain 222 may be due to increased production of triose phosphate, some of which is converted to methylglyoxal.
17 citations
Journal Article•
TL;DR: The data suggest that a phenotypic alteration in mitochondrial function, rather than in polyamine metabolism, may represent the basis for MGBG resistance in these variant cell lines.
Abstract: Stable variants of the human cell line, VA2-B, have been developed which are 10- to 20-fold less sensitive to the antiproliferative effects of methylglyoxal bis(guanylhydrazone) (MGBG) than the parent cell line and which are not drug transport deficient. The lines were characterized biochemically giving particular attention to parameters related to the two known sites of MGBG action, mitochondria and polyamine metabolism. Doseresponse studies with MGBG (0 to 30 µm for 40 to 48 hr) revealed that, of the parameters related to polyamine metabolism ( i.e. , polyamine pools, S -adenosylmethionine, and ornithine decarboxylase activities), only spermine pool size reduction seemed to correlate with inhibition of cell growth by MGBG. By contrast, decreases in pyruvate oxidation (used here as a measure of mitochondrial function) closely paralleled growth inhibition in all cell lines. Similarly, MGBG-induced changes in mitochondrial ultrastructure were less conspicuous in the variants than in the parent cell line and also corresponded with growth inhibition. Respiration of isolated mitochondria from one of the variant lines was about 2-fold more resistant to the inhibitory effects of MGBG than mitochondria from the VA2 cells. Finally, treatment with α-difluoromethylornithine, a potent inhibitor of polyamine biosynthesis having no known effect on mitochondrial function, resulted in comparable inhibition of growth in variant and parent cell lines. Overall, the data suggest that a phenotypic alteration in mitochondrial function, rather than in polyamine metabolism, may represent the basis for MGBG resistance in these variant cell lines.
15 citations
TL;DR: Methylglyoxal is successfully converted to the tin(II) enediolate on treatment with activated metallic tin and reacts with several aldehydes to give α, β-dihydroxyketones in good yields.
Abstract: Methylglyoxal is successfully converted to the tin(II) enediolate on treatment with activated metallic tin. The tin(II) enediolate reacts with several aldehydes to give α, β-dihydroxyketones in good yields.
TL;DR: Experiments in which one of these blocks was imposed as the other was released confirmed that cells blocked by methylglyoxal bis(guanylhydrazone) are arrested at an earlier stage in G1 than cells block by calcium deprivation.
Abstract: Methylglyoxal bis(guanylhydrazone) completely inhibits the induction of thymidine kinase after serum stimulation of quiescent fibroblasts only if added within 3 h after serum, whereas calcium deprivation blocks this induction up to 12 h after serum stimulation. Experiments in which one of these blocks was imposed as the other was released confirmed that cells blocked by methylglyoxal bis(guanylhydrazone) are arrested at an earlier stage in G1 than cells blocked by calcium deprivation.
TL;DR: Mitochondrial structure and function were studied in 9L rat brain tumor cells depleted of polyamines by alpha-difluoromethylornithine, an enzyme-activated irreversible inhibitor of ornithine decarboxylase, and cells treated with methylglyoxal bis(guanylhydrazone), a reversible inhibitor of S-adenosylmethioninedecarboxyase were used for comparison.
Abstract: Mitochondrial structure and function were studied in 9L rat brain tumor cells depleted of polyamines by α-difluoromethylornithine, an enzyme-activated irreversible inhibitor of ornithine decarboxylase. Cells treated with methylglyoxal bis(guanylhydrazone), a reversible inhibitor of S-adenosylmethionine decarboxylase, were used for comparison because this polyamine biosynthesis inhibitor is known to cause structural and functional disruption of mitochondria. A significant increase in mitochondrial size, measured quantitatively, was found in α-difluoromethylornithine-treated cells (10 mM for 72 hr) compared with untreated cells (P < 0.001). This increase in mitochondrial size was reversed when putrescine was added to the cultures for 24 hr after α-difluoromethylornithine treatment. Putrescine alone had no effect on the size of mitochondria. Treatment of cells with methylglyoxal bis(guanylhydrazone) (80 μM for 48 hr) caused only a slight increase in mitochondrial size compared with mitochondria in untreated cells (P < 0.05) and failed to produce the dramatic ultrastructural changes reported in other cell lines. Ultrastructural examination revealed an increase in cytoplasmic and membrane-associated ribosomes in α-difluoromethylornithine-treated cells, an increase in cytoplasmic ribosomes in methylglyoxal bis(guanylhydrazone)-treated cells, and an increase in membrane-bound ribosomes in putrescine-treated cells. In cells treated first with α-difluoromethylornithine and then with putrescine, the distribution of ribosomes was normal. The distributions of ribosomes were not quantitatively assessed. Pyruvate utilization, a measure of mitochondrial function, was decreased in cells treated with 10 mM α-difluoromethylornithine for 72 hr, compared with untreated cells. Restoration of intracellular polyamine levels by the addition of putrescine 24 hr before analysis reversed this phenomenon. Putrescine treatment alone did not affect pyruvate utilization. Pyruvate utilization in methylglyoxal bis(guanylhydrazone)-treated cells was depressed to a greater extent than that in α-difluoromethylornithine-treated cells.
TL;DR: Inhibition of methylglyoxal catabolism suggests possible application as chemotherapeutic agents based on the inhibitor characteristics of methyl Glyoxal.
TL;DR: Convergence of the double reciprocal plots and the pattern of inhibition by products and by acetone, a substrate analog, demonstrate that glyoxal reduction—and most likely that of diacetyl—proceeds via an ordered Bi-Bi mechanism in which NADPH is fixed before the addition of the carbonyl.
Patent•
12 Nov 1983
TL;DR: In this paper, the authors proposed a method to obtain the titled substance by bringing methylglyoxal into contact with ammonium oxalate, formaldehyde and water, removing partially the water, adding an alcohol thereto, filtering the oxalates of the resulting product, and removing the Oxalic acid from the resultant product.
Abstract: PURPOSE: To obtain the titled substance, by bringing methylglyoxal into contact with ammonium oxalate, formaldehyde and water, removing partially the water, adding an alcohol thereto, filtering the oxalate of the titled substance, and removing the oxalic acid from the resultant product. CONSTITUTION: Methylglyoxal is added to an aqueous solution of ammonium oxalate and formaldehyde, etc. to carry out the reaction, and the water is then removed to an amount equal to that of the methylglyoxal or below. An alcohol, e.g. methanol or ethanol, is added to the reaction mixture, and the oxalate of the titled substance in filtered. Oxalic acid is then removed from the resultant reaction product to afford the titled subtance. The amount of the water in bringing the methylglyoxal into contact with the ammonium oxalate, etc. is 4W30 times, preferably 5W15 times of that of the methylglyoxal. Preferably, the oxalate of 4-methylimidazole is subjected to the removal of the oxalic acid with an aqueous ammonia, and the resultant ammonium oxalate is circulated for use. COPYRIGHT: (C)1985,JPO&Japio
TL;DR: In this paper, the physiological effect of methylglyoxal (CH3COCHO) on the living cell, the enzymes responsible for the synthesis and the turnover of methyl glyoxal including the environmental conditions necessary for the accumulation of lethal concentrations in the medium.
Abstract: Methylglyoxal (CH3COCHO) is a toxic intermediate of the carbon metabolism. Its accumulation in the growth medium of microorganisms may be an important danger for many fermentation processes. In this paper data will be presented which show the physiological effect of this compound on the living cell, the enzymes responsible for the synthesis and the turnover of methylglyoxal including the environmental conditions necessary for the accumulation of lethal concentrations in the medium.
TL;DR: Glyoxalase I activity can be determined in crude tissue preparations without interference from biological materials and its values found in millimolar hemimercaptal were about 0.5.
Patent•
12 Nov 1983
TL;DR: In this article, the use of 4W30 times, especially 5W15 times as much water as methylglyoxal of raw material, was used to give 4methylimidazole.
Abstract: PURPOSE: To prepare-4-methylimidazole in high purity in high yield, by reacting methylglyoxal with ammonium oxalate and formaldehyde by the use of a specific amount of water in a water medium. CONSTITUTION: By the use of 4W30 times, especially 5W15 times as much water as methylglyoxal of raw material, methylglyoxal is added to an aqueous solution of ammonium oxalate and formaldehyde, or a mixed solution of methlylyaxal and formaldehyde is added to an aqueous solution of ammonium oxalate, or methylglyoxal and formaldehyde are simultaneously added to it, or the mixed solution of methylglyoxal and formaldehyde and ammonium oxalate are simultaneously added to water previously prepared, or three raw materials are simultaneously added to the water, and the reaction is carried out to give 4-methylimidazole. EFFECT: Low-grade methylglyoxal may be used. COPYRIGHT: (C)1985,JPO&Japio
Patent•
24 Nov 1983
TL;DR: In this paper, a process for the preparation of pyruvic acid by oxidising methylglyoxal in aqueous solution with bromine is described. But this process requires a large amount of methyl glyoxal.
Abstract: Process for the preparation of pyruvic acid by oxidising methylglyoxal in aqueous solution with bromine.