Showing papers on "Methylglyoxal published in 1980"
TL;DR: Inhibition of polyamine synthesis by alpha-difluoromethylornithine in cultured Ehrlich ascites-carcinoma cells rapidly enhanced the uptake of exogenous putrescine, spermidine and spermine from the culture medium.
Abstract: Inhibition of polyamine synthesis by alpha-difluoromethylornithine in cultured Ehrlich ascites-carcinoma cells rapidly enhanced the uptake of exogenous putrescine, spermidine and spermine from the culture medium. In tumour cells exposed to the drug for 2 days, the intracellular concentration of spermidine was decreased to less than 10% of that found in untreated cells. However, the strikingly stimulated transport system brought the concentration of spermidine to the control values in less than 2h after supplementation of the cells with micromolar concentrations of the polyamine. In the absence of polyamine deprivation, tumour cells did not accumulate extracellular polyamines to any appreciable extent. Ascites-tumour cells deprived of putrescine and spermidine likewise concentrated methylglyoxal bis(guanylhydrazone) [1,1′-[methylethanedylidine)dinitrilo]diguanidine] at a greatly enhanced rate. A previous “priming of tumour cells with difluoromethylornithine followed by an exposure of the cells to methylglyoxal bis(guanylhydrazone) resulted in a marked and rapid anti-proliferative effect.
175 citations
TL;DR: Although an enzyme system capable of converting acetone into acetol has not been detected, the inclusion of acetol in the pathway is supported by the results of studies with whole cells and [14C]acetone.
Abstract: Four Gram-positive bacteria have been isolated from separate soil samples by enrichment culture with acetone as sole source of carbon. Whole cells of all strains grown on acetone rapidly oxidized acetone, acetol and methylglyoxal, and three of the four also oxidized isopropanol. The patterns of induced enzymes in cell extracts are compatible with the oxidation sequence: isopropanol → acetone → acetol → methylglyoxal → pyruvate. Although an enzyme system capable of converting acetone into acetol has not been detected, the inclusion of acetol in the pathway is supported by the results of studies with whole cells and [14C]acetone. The proposed pathway of acetone metabolism is contrasted with evidence for an alternative, but not fully understood, pathway used by Mycobacterium vaccae JOB5.
100 citations
TL;DR: Since all glycolytic enzymes,except triose- phosphate isomerase, contain essential arginine resi- dues, it seemed worthwhile to compare the effect of methylglyoxal on the enzymes of the glyco- lytic pathway.
54 citations
TL;DR: It is concluded that the primary step in the reaction involves the formation of a Schiff base linkage between the lysine side chain and methylglyoxal, reaffirm the concept that aldehydes can act as electron acceptors in charge transfer interactions with proteins.
Abstract: Spectroscopic measurements are reported for the effects of pH, time, solvent, and chemical modification of arginine and lysine side chains on the reaction of proteins with methylglyoxal. The reaction responsible for the appearance of a brown coloration and increased submolecular electronic activity in the proteins involves the epsilon-amino groups of the lysine residues. It is concluded that the primary step in the reaction involves the formation of a Schiff base linkage between the lysine side chain and methylglyoxal. These findings reaffirm the concept that, by the formation of Schiff bases, aldehydes can act as electron acceptors in charge transfer interactions with proteins.
47 citations
TL;DR: Regular determination of the cellular drug concentrations indicated that methylglyoxal bis(guanylhydrazone) could be given as weekly infusions, which represents much lower dosing of the drug than the earlier daily regimens which were commonly associated with unacceptable toxicity.
Abstract: Methylglyoxal bis(guanylhydrazone), a cytostatic compound which apparently interferes with the metabolism and/or functions of the natural polyamines (spermidine and spermine), was effectively taken up by cultured human lymphocytic leukemia cells, rapidly resulting in the formation of a concentration gradient of up to 1,000-fold across the cell membrane in cells grown in the presence of micromolar concentrations of the drug. For an anti-proliferative effect on the leukemia cells, an intracellular concentration of more than 0.5 mm was required. The uptake of methylglyoxal bis-(guanylhydrazone) was critically dependent on the growth rate of the leukemia cells. Low intracellular concentrations of the drug were present in cells growing slowly, whereas in rapidly dividing cells the intracellular concentration of the drug approached 5 mm. When given as repeated intravenous infusions to two leukemic children, methylglyoxal bis(guanylhydrazone) exhibited sharp and transient peaks of plasma concentration, the drug having an apparent half-life in plasma of only 1-2 h. However, as in cultured cells, the drug was rapidly concentrated in the leukemia cells, reaching concentrations that were distinctly anti-proliferative. In contrast to the rapid disappearance of methylglyoxal bis(guanylhydrazone) from plasma, the circulation leukemia cells retained the drug for a period of several days with only minimal decrease in the initial concentrations. Methylglyoxal bis(guanylhydrazone) was given to the patients for 1 to 2 months as intravenous infusions, the timing of which was determined by regular assays of the drug concentrations in the leukemia cells. In agreement with the results obtained with the cultured cells, an intracellular concentration of about 0.5 to I mm was apparently required for growth-inhibitory action to occur. Regular determination of the cellular drug concentrations indicated that methylglyoxal bis(guanylhydrazone) could be given as weekly infusions. This treatment schedule represents much lower dosing of the drug than the earlier daily regimens which were commonly associated with unacceptable toxicity.
25 citations
TL;DR: A methyl glyoxal-resistant mutant of Escherichia coli B excreted glutathione into the growth medium, especially during growth on medium containing methylglyoxal, which appeared to be due to the simultaneous increase in the activities of these two enzyme systems.
Abstract: A methylglyoxal-resistant mutant of Escherichia coli B excreted glutathione into the growth medium, especially during growth on medium containing methylglyoxal. In the presence of methylglyoxal, the total amount of glutathione excreted was increased about 50-fold over that of the wild-type strain. The resistant mutant had high activities of two enzyme systems: a glutathione-forming enzyme system (consisting of gamma-glutamylcysteine synthetase and glutathione synthetase) and a glyoxalase system (consisting of glyoxalase I and glyoxalase II). Methylglyoxal resistance appeared to be due to the simultaneous increase in the activities of these two enzyme systems.
25 citations
22 citations
TL;DR: In the presence of a magnetic field, the faster of the two sloow components of the fluorescence of methylglyoxal decreases in intensity while the slower component is unaffected, and a new component with a lifetime of about 40 ns appears as mentioned in this paper.
18 citations
TL;DR: The results indicate that the mode of action of 1,1'-[(methylethanediylidene)dinitrilo]bis-(3-aminoguanidine) is fully comparable to that of methylglyoxal bis(guanylhydrazone), as regards stabilization of adenosylmethionine decarboxylase and the appearance of growth inhibition in Ehrlich ascites cells.
Abstract: The anti-proliferative effects of 1,1'-[(methylethanediylidene)dinitrilo]diguanidine [methylglyoxal bis(guanylhydrazone)] and 1,1'-[(metHYLETHANEDIYLIDENE)dinitrilo]bis-(3-aminoguaNIDINE) HAVE BEEN STUDIED IN Ehrlich ascites carcinoma cells grown in suspension cultures. Both compounds are potent inhibitors of S-adenosyl-L-methionine decarboxylase from the tumour cells. In the presence of putrescine (but not in its absence), the inhibition produced by 1,1'-[methylethanediylidene)dinitrilo]bis-(3-aminoguanadine) was apparently irreversible, as judged by persistent depression of the enzyme activity even after extensive dialysis. The two compounds produced similar increases in adenosylmethionine decarboxylase activity, which resulted from a striking stabilization of the enzyme in cells grown in the presence of the drugs. The inhibitory effect of the two diguanidine derivatives on the synthesis of DNA and protein became evident after an exposure of 4--8 h. At that time, the only change seen in tumour polyamines in cells grown in the presence of the inhibitors was an increase in cellular putrescine. To find out whether the compounds initially interfered with the energy production of the tumour cells, the cultures were grown in the presence of uniformly labelled glucose, and the formation of lactate, as well as the oxidation of the sugar into CO2, were measured. The activation of glycolysis upon dilution of the tumour cells with fresh medium and the subsequent formation of labelled CO2 were siliar in control cells and in cells exposed to methylglyoxal bis(buanylhydrazone), 1,1'-[(methylethanediylidene)dinitrilo]bis-(3-aminoguanidine) or diaminopropanol. Only a marginal decrease in the cellular content of ATP was found in cells exposed to the inhibitors for 24 h. The diguanidine-induced growth inhibition was fully reversed by low concentrations of exogenous polyamines. However, the possibility remained that the reversal by polyamines was due to a decrease of intracellular diguanidine concentration. Our results indicate that the mode of action of 1,1'-[(methylethanediylidene)dinitrilo]bis-(3-aminoguanidine) is fully comparable to that of methylglyoxal bis(guanylhydrazone), as regards stabilization of adenosylmethionine decarboxylase and the appearance of growth inhibition in Ehrlich ascites cells. The data tend to support the view that both compounds apparently have an early anti-proliferative effect unrelated to polyamine metabolism.
17 citations
TL;DR: The presence at rest and the rise in blood after exercise of two metabolites of the aminoacetone pathway of amino acid degradation in man and the possible physiologic significance of the assumed amino acetone pathway was discussed with respect to muscular activity.
Abstract: The following article reports (A) data on glyoxalase I activity in skeletal muscle of untrained men and endurance--trained athletes, and (B) the presence at rest and the rise in blood after exercise of two metabolites of the aminoacetone pathway of amino acid degradation in man. Glyoxalase I showed an average activity of 191 +/- 38 U/g wet weight (37 degrees C) in bioptic samples of m.vastus medialis quadricipitis of young adults whereas this was of 235 +/- 64 U/g (p < 0.15) in athletes. After an ergometer exercise test with increasing intensity (50 to 400 Watt (W), 3 min-steps) by well trained cyclists, blood (L-(+)-lactate increased to 10.12 mmole/liter, whereas methylglyoxal rose by 48.4% and D-(-)-lactate by 70% (resting levels 92 and 100/mumole/liter, respectively). The possible physiologic significance of the assumed aminoacetone pathway was discussed with respect to muscular activity.
17 citations
TL;DR: The results indicate that the structural requirements for binding of methylglyoxal bis(guanylhydrazone) to the enzyme are strict and that structural modifications of this compound result in a dramatic loss of activity.
TL;DR: The drug caused extensive deletions in mitochondrial DNA detected by an increase in the frequency of the mitochondrial mutant petite but had little or no effect on cell viability.
Abstract: Primary action of methylglyoxal bis(guanylhydrazone) (MGBG) on the yeast mitochondrial system was demonstrated by (1) selective inhibition of cell growth in non-fermentable medium, (2) blockage of mitochondrial synthesis of cytochromes aa3
and b and (3) ultrastructural aberration. The drug caused extensive deletions in mitochondrial DNA detected by an increase in the frequency of the mitochondrial mutant petite but had little or no effect on cell viability. Growth inhibition by MGBG was antagonized by spermidine but neither the polyamine nor MGBG had any effect on growth inhibition by ethidium bromide. Strains showed no cross-correlation in their tolerance to MGBG and ethidium bromide.
Journal Article•
TL;DR: Reaction of rabbit muscle fructose 1,6-P2 aldolase with methylglyoxal results in a biphasic loss of activity and data suggest that probably one of these arginine residues is essential and could be its interaction with the C1 negatively charged phosphate binding site of the enzyme.
Abstract: Reaction of rabbit muscle fructose 1,6-P2 aldolase with methylglyoxal results in a biphasic loss of activity. The kinetics of the initial rapid phase are first order with respect to the inhibitor. Dihydroxyacetone phosphate and fructose 1,6 bisphosphate afford complete protection whereas inorganic phosphate provides only a partial protection against inactivation. The treatment with methylglyoxal modifies the aldolase ability to bind D-Ga3P and DHAP. Loss of activity correlates with the modification of 1.7 arginine residues but data suggest that probably one of these arginine residues is essential. A likely role of this residue could be its interaction with the C1 negatively charged phosphate binding site of the enzyme.
TL;DR: S-(p-azidophenacyl)-glutathione, l, is a linear competitive inhibitor at pH 7.40 of beef liver glyoxalase II with Ki = 7.96 × 10−4 M that covalently inhibits glyoxAlase II to a level of 42 ± 5% inhibition.
TL;DR: Exposure of the cells to methylglyoxal bis(guanylhydrazone) during growth phase caused a dose-dependent fall in intracellular spermidine and spermine levels and an increase in putrescine levels at higher concentrations.
Abstract: The putrescine, spermidine, and spermine content of subcultured human newborn foreskin keratinocytes was determined during growth and early plateau phase and found to be highest during growth. Exposure of the cells to methylglyoxal bis(guanylhydrazone) during growth phase caused a dose-dependent fall in intracellular spermidine and spermine levels and an increase in putrescine levels at higher concentrations. These effects reflect inhibition of S-adenosyl methionine decarboxylase by the drug. At 8×10-6 M the drug reduced incorporation of leucine into protein, lowered or stopped the accumulation of DNA per dish, inhibited mitotic activity, and increased the histidine/leucine incorporation into protein. The last effect is regarded as induction of keratinization. All these effects were reversible if the use of the drug was discontinued after 3 days. Inhibition of the enzymes of polyamine biosynthesis may have value in psoriasis therapy.
TL;DR: Nuclear magnetic resonance measurements show that the methylglyoxal polymer interacts with the polypeptide via the NH groups of peptide bonds.
TL;DR: It is demonstrated that partially purified aminopropyltr~sfera~s from rat liver were strongly inhibited by SAM and that administration of SAM in combination with methylglyoxal bis(guanylhydrazone) (MGBG) caused a decrease in the concentration of spermid~e, which may be useful for understanding the regulation of polyamine synthesis in eukaryotic cells.
Patent•
04 Jul 1980
TL;DR: Methyl glyoxal is manufactured continuously by passing glycerol in the gaseous phase over a heterogeneous dehydrogenation catalyst as discussed by the authors, but it is not known how to make it more stable.
Abstract: Methylglyoxal is manufactured continuously by passing glycerol in the gaseous phase over a heterogeneous dehydrogenation catalyst.
01 Jan 1980
TL;DR: A methyl glyoxal-resistant mutant of Escherichia coli B excreted glutathione into the growth medium, especially during growth on medium containing methylglyoxal, which appeared to be due to the simultaneous increase in the activities of these two enzyme systems.
Abstract: A methylglyoxal-resistant mutant of Escherichia coli B excreted glutathione into the growth medium, especially during growth on medium containing methylglyoxal. In the presence of methylglyoxal, the total amount of glutathione excreted was increased about 50-fold over that of the wild-type strain. The resistant mutant had high activities of two enzyme systems: a glutathione-forming enzyme system (consisting of y-glutamylcysteine synthetase and glutathione synthetase) and a glyoxalase system (consisting of glyoxalase I and glyoxalase 11). Methylglyoxal resistance appeared to be due to the simultaneous increase in the activities of these two enzyme systems.