Showing papers on "Methylglyoxal published in 1984"
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TL;DR: The data suggest that acetone both acts to induce a critical enzyme or enzymes and serves as a precursor for the production of 1,2-propanediol, and it is also clear that chronic acetone feeding plays a role in 2,3-butanediol production in the rat.
271 citations
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TL;DR: A bypass of the EMBDEN·MEYERHOF PATHWAy using the Glyoxalase System for the UTILIZation of Methylglyoxal and its results show the importance of knowing the carrier and removal mechanisms.
Abstract: INTRODUCTION 49 A METHYl.GLYOXAL BYPASS OF THE EMBDEN·MEYERHOF PATHWAy...... 51 CYTOTOXIC NATURE OF METHYLGLYOXAL ........ 54 ENZYMA TJ[C FORMATION OF METHYLGLYOXAL 54 Studies on Methylglyoxal Synthase 54 Glyceraldehyde 3.Phosphate and Glyceraldehyde as Possible Precursors of Methylglyoxal 57 Acetol Dehydrogenase 57 Methylglyoxal from Aminoacetone 58 REACTIONS FOR THE UTILIZATION OF METHYLGLYOXAL 58 The Glyoxalase System 58 Methylg,yoxal Dehydrogen ase 60 Formaldehyde Dehydrogenase 60
255 citations
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TL;DR: The hypothesis of a carcinogenic effect of the aldehydic products released in biomembranes during lipid peroxidation is supported.
Abstract: Alkaline elution was employed to study DNA damage in CHO-Kl cells treated with a series of biotic and xenobiotic aldehydes. DNA cross-linking was measured in terms of the reduction in the effect of methyl methanesulphonate on the kinetics of DNA elution and was observed in cells treated with formaldehyde, acetaldehyde, methylglyoxal and malonaldehyde. Propionaldehyde, valeraldehyde, hexanal and 4-hydroxynonenal produced DNA single-strand breaks, or lesions which were converted to breaks in alkali. Both types of DNA damage occurred in cells exposed to malealdehyde. These findings support the hypothesis of a carcinogenic effect of the aldehydic products (malonaldehyde, methylglyoxal, propionaldehyde, hexanal, 4-hydroxynonenal) released in biomembranes during lipid peroxidation.
82 citations
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TL;DR: The uptake of exogenously administered radiolabeled polyamines by a rat prostate-derived tumor line, the Dunning R3327 MAT-Lu, and various normal tissues was studied and methylglyoxal bis(guanylhydrazone), which utilizes the polyamine transport system for uptake into cells, exhibited uptake behavior different from that of the polyamines.
Abstract: The uptake of exogenously administered radiolabeled polyamines by a rat prostate-derived tumor line, the Dunning R3327 MAT-Lu, and various normal tissues was studied. Pretreatment of tumor cells in vitro with alpha-difluoromethylornithine (DFMO), a polyamine synthesis inhibitor, resulted in a markedly enhanced uptake of both [14C]putrescine and [14 C]spermidine. The in vitro uptake of [14C]putrescine by these cells was effectively inhibited by unlabeled spermine, spermidine, 1,8-diaminooctane, 1,7-diaminoheptane, 1,6-diaminohexane, 1,5-diaminopentane, 1,4-diaminopentane, and 1,4-diaminobutane, but less effectively by 1,4-diamino-2,3-butene and 1,4-diamino-2,3-butyne. The diamines, 1,3-diaminopropane and 1,2-diaminoethane, were ineffective in inhibiting [14C]putrescine uptake in vitro into the R3327 MAT-Lu cell line. When tumor-bearing animals were pretreated with DFMO or with DFMO and 5-alpha-dihydrotestosterone propionate, the tumor and prostate uptake of [14C]putrescine and [14C]-cadaverine was enhanced but not substantially increased in other tissues. In contrast to the in vitro results, spermidine and spermine were not enhanced substantially by DFMO pretreatment into any tissue, and their uptake into the tumor actually decreased. Ethylenediamine, which does not utilize the polyamine transport system, did not have its uptake increased into any tissue following DFMO pretreatment. The chemotherapeutic agent, methylglyoxal bis(guanylhydrazone), which utilizes the polyamine transport system for uptake into cells, exhibited uptake behavior different from that of the polyamines. Thus, methylglyoxal bis(guanylhydrazone) uptake into the tumor was not significantly increased or decreased by DFMO or by DFMO + 5-alpha-dihydrotestosterone propionate pretreatment, and only the ventral, but not the dorsal-lateral, lobe of the prostate showed increased uptake of methylglyoxal bis(guanylhydrazone) following DFMO + 5-alpha-dihydrotestosterone propionate pretreatment.
45 citations
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TL;DR: With the addition of mitotic inhibitors, vinblastine and methylglyoxal in the growth medium, the enzyme activity was inhibited by 92 percent and 50 percent respectively, at the most effective concentration and the callus growth was also reduced.
Abstract: Glyoxalase-I activity in growingDatura callus showed 184% increase with the age of the culture. Spermidine increased the enzyme activity together with DNA and protein synthesis. With the addition of mitotic inhibitors, vinblastine and methylglyoxal in the growth medium, the enzyme activity was inhibited by 92 percent and 50 percent respectively, at the most effective concentration and the callus growth was also reduced. Similar results were obtained with specific glyoxalase I inhibitors, iso-ascorbate and squaric acid.
43 citations
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TL;DR: The inactivation by p-chloromercuribenzoate could be substantially protected by methylglyoxal in combination with NADH, indicating a possible involvement of one or more sulfhydryl group(s) at the active site of the enzyme.
43 citations
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TL;DR: EGBG is more suitable as a specific inhibitor of polyamine biosynthesis and that use of this drug, rather than MGBG, in combination with alpha-difluoromethylornithine may be useful for studying the physiological functions of polyamines in animal cells.
Abstract: Ethylglyoxal bis(guanylhydrazone) (EGBG) was compared as an inhibitor of polyamine biosynthesis with methylglyoxal bis(guanylhydrazone) (MGBG) in bovine small lymphocytes stimulated by concanavalin A. EGBG brought about a decrease in spermidine and spermine levels equal to that found with MGBG, but at a 5-fold lower intracellular drug concentration. Despite identical polyamine levels, the degree of inhibition of DNA and protein synthesis by EGBG was smaller than that observed with MGBG, in either the presence or absence of the ornithine decarboxylase inhibitor, alpha-difluoromethylornithine. It was found that in vitro protein synthesis and in vivo mitochondrial function were inhibited by concentrations of MGBG necessary to inhibit polyamine synthesis in cells (1 to 3 mM), but not by efficacious levels of EGBG (0.2 to 0.6 mM). These results suggest that EGBG is more suitable as a specific inhibitor of polyamine biosynthesis and that use of this drug, rather than MGBG, in combination with alpha-difluoromethylornithine may be useful for studying the physiological functions of polyamines in animal cells.
35 citations
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TL;DR: Taking into consideration the proven anti-leukaemic activity of glyoxal bis(guanylhydrazone), its effectiveness to inhibit spermidine biosynthesis (without raising the concentration of putrescine) as well as its suitability for combined use with inhibitors of ornithine decarboxylase, this drug is apparently worthy of further testing in tumour-bearing animals, especially in combination with difluoromethylornithine.
Abstract: Glyoxal bis(guanylhydrazone), the parent compound of methylglyoxal bis(guanylhydrazone), was synthesized and tested for its ability to inhibit the biosynthesis of polyamines. It was found to be a powerful competitive inhibitor of adenosylmethionine decarboxylase (EC 4.1.1.50), yet the lack of the methyl group at the glyoxal portion increased the apparent Ki value for the enzyme by about 30-fold in comparison with methylglyoxal bis(guanylhydrazone). Glyoxal bis(guanylhydrazone) inhibited diamine oxidase (EC 1.4.3.6) activity as effectively as did methylglyoxal bis(guanylhydrazone). The cellular accumulation curves of glyoxal bis(guanylhydrazone) in L1210 cells were practically superimposable with those of methylglyoxal bis(guanylhydrazone), and the uptake of both compounds was distinctly stimulated by a prior treatment with 2-difluoromethylornithine. The drug decreased the concentration of spermidine in a dose-dependent manner and, in contrast with methylglyoxal bis(guanylhydrazone), without a concomitant accumulation of putrescine. The fact that putrescine concentrations were decreased in cells exposed to glyoxal bis(guanylhydrazone) was, at least in part, attributable to an inhibition of ornithine decarboxylase (EC 4.1.1.17) activity in cells treated with the compound. Under these experimental conditions equivalent concentrations of methylglyoxal bis(guanylhydrazone) [1,1'-[(methylethanediylidine)dinitrilo]diguanidine] elicited large increases in the enzyme activity. When combined with difluoromethylornithine, glyoxal bis(guanylhydrazone) potentiated the growth-inhibitory effect of that drug. Taking into consideration the proven anti-leukaemic activity of glyoxal bis(guanylhydrazone), its effectiveness to inhibit spermidine biosynthesis (without raising the concentration of putrescine) as well as its suitability for combined use with inhibitors of ornithine decarboxylase, this drug is apparently worthy of further testing in tumour-bearing animals, especially in combination with difluoromethylornithine or related inhibitors of ornithine decarboxylase.
28 citations
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TL;DR: Coffee showed mutagenic activity in cultured Chinese hamster lung (CHL) cells as assessed by using diphtheria toxin resistance as a selective marker, and most of the mutagenicity was suppressed in the presence of sodium bisulfite.
28 citations
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TL;DR: Several congeners of methylglyoxal bis(guanylhydrazone) were tested for their ability to inhibit eukaryotic putrescine-activated S-adenosylmethionine decarboxylase and intestinal diamine oxidase activity in vitro, and both derivatives appeared to utilize the polyamine-carrier system.
Abstract: Several congeners of methylglyoxal bis(guanylhydrazone) were tested for their ability to inhibit eukaryotic putrescine-activated S-adenosylmethionine decarboxylase (EC 4.1.1.50) and intestinal diamine oxidase (EC 1.4.3.6). All the compounds tested, namely methylglyoxal bis(guanylhydrazone), ethylglyoxal bis(guanylhydrazone), dimethylglyoxal bis(guanylhydrazone) and the di-N"-methyl derivative of methylglyoxal bis(guanylhydrazone), were strong inhibitors of both yeast and mouse liver adenosylmethionine decarboxylase activity in vitro. The enzyme from both sources was most powerfully inhibited by ethylglyoxal bis(guanylhydrazone). All the diguanidines likewise inhibited diamine oxidase activity in vitro. The maximum intracellular concentrations of the ethyl and dimethylated analogues achieved in activated lymphocytes were only about one-fifth of that of the parent compound. However, both derivatives appeared to utilize the polyamine-carrier system, as indicated by competition experiments with spermidine.
25 citations
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TL;DR: Ethylglyoxal bis(guanylhydrazone) was growth-inhibitory to L1210 cells and produced an additive antiproliferative action when used together with 2-difluoromethylornithine.
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TL;DR: It is suggested that the reaction potentialities of the oxaldehyde function of the inhibitors play an important role in their growth-inhibitory acitivity, besides exerting a specific effect on hexokinase (glucosone) and UTP-trapping activity.
Abstract: 1.
Proliferation of in vitro grown Ehrlich ascites tumor cells is completely inhibited by 0.2–0.4 mM methylglyoxal and 1–2mM glucosone or galactosone without severely affecting viability (dye exclusion test); no phase-specific arrest of cell growth is observed.
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Incorporation of [14C] thymidine into the acid-insoluble fraction of the cells decreases within a few minutes to less than 50% of that in controls in the presence of 0.4 mM methylglyoxal, and 2 mM glucosone or galactosone causes a comparable inhibition of DNA synthesis after 2 h or 4 h, respectively.
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The action of 0.4 mM methylglyoxal inhibits incorporation of [14C] leucine within a few minutes by more than 70%, while 2 mM glucosone and galactosone are significantly less effective (50%–60% inhibition after 12 h).
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While methylglyoxal and galactosone do not severely affect lactate production of the cells, 2 mM glucosone reduces glycolysis by 60%–70%; ATP/ADP ratios did not fall below 3.5 in the presence of the inhibitors (controls 4–6).
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It is suggested that the reaction potentialities of the oxaldehyde function of the inhibitors play an important role in their growth-inhibitory acitivity, besides exerting a specific effect on hexokinase (glucosone) and UTP-trapping activity.
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TL;DR: Treatment of Ehrlich-ascites-carcinoma-bearing mice with methylglyoxal bis(guanylhydrazone) alone or in combination with 2-difluoromethylornithine greatly enhanced the transfer of intragastrically administered radioactive putrescine and cadaverine into the carcinoma cells.
Abstract: Treatment of Ehrlich-ascites-carcinoma-bearing mice with methylglyoxal bis(guanylhydrazone) alone or in combination with 2-difluoromethylornithine greatly enhanced the transfer of intragastrically administered radioactive putrescine and cadaverine into the carcinoma cells. Difluoromethylornithine alone did not have any effect on the accumulation of intestine-derived diamines in the tumour cells. The frequently reported restoration of difluoromethylornithine-induced polyamine depletion on administration of methylglyoxal bis(guanylhydrazone) is in all likelihood attributable to a profound inhibition of intestinal diamine oxidase (EC 1.4.3.6), resulting in an enhanced entry of intestinal (bacterial) diamines into general circulation and finally into tumour cells.
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TL;DR: The finding indicating that MGBG impairs fatty acid utilization may be an explanation for the known hypoglycemic effect produced by the drug in most animal species as well as for some of the side-effects associated with its clinical use, most notably severe myalgia.
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TL;DR: The results indicate that a combined use of these two polyamine anti-metabolites does not necessarily result in a synergistic growth inhibition of the androgen-induced growth of male accessory sexual glands.
Abstract: 2-Difluoromethylornithine totally prevented any increases in putrescine and spermidine concentrations in the ventral prostate of castrated rats during a 6-day testosterone treatment. Prostatic ornithine decarboxylase activity was inhibited by 80%, whereas S-adenosylmethionine decarboxylase was stimulated by more than 9-fold. In seminal vesicle, the inhibition of putrescine and spermidine accumulation, as well as of ornithine decarboxylase activity, was only minimal, and no stimulation of S-adenosylmethionine decarboxylase was observed. Administration of methylglyoxal bis(guanylhydrazone) to castrated androgen-treated rats resulted in a marked increase in concentrations of all prostatic polyamines. Prostatic ornithine decarboxylase activity was nearly 2 times and adenosylmethionine decarboxylase activity 9 times higher than that of the testosterone-treated animals. In contrast with ventral prostate, methylglyoxal bis(guanylhydrazone) treatment inhibited moderately the accumulation of spermidine and spermine in seminal vesicle, although both ornithine decarboxylase and S-adenosylmethionine decarboxylase activities were stimulated. Difluoromethylornithine inhibited significantly the weight gain of ventral prostate, but methylglyoxal bis(guanylhydrazone) produced a substantial increase in prostatic weight. These changes were largely due to the fact that the volume of prostatic secretion was greatly decreased by difluoromethylornithine, whereas methylglyoxal bis(guanylhydrazone) increased the amount of secretion. Treatment with difluoromethylornithine strikingly increased the methylglyoxal bis(guanylhydrazone) content of both ventral prostate and seminal vesicle, but even under these conditions the drug concentration remained low in comparison with other tissues. The results indicate that a combined use of these two polyamine anti-metabolites does not necessarily result in a synergistic growth inhibition of the androgen-induced growth of male accessory sexual glands.
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TL;DR: For the mitochondrial enzyme, the inhibition with methylglyoxal was more pronounced at higher pH values, whereas stronger inhibition was observed with glyceraldehyde 3-phosphate at physiological pH, which has been found to be stronger for the cytosolic enzyme at pH values higher than the physiological pH.
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TL;DR: Based on previous research from these laboratories various structural analogs of 3-hydroxyflavone were tested for inhibition of glyoxalse I, and the most inhibitory compound in vitro was myricetin, which has a 3′,4′,5′-trihydroxyphenolic ring at the 2 position of the pyrone ring.
Abstract: Based on previous research from these laboratories various structural analogs of 3-hydroxyflavone were tested for inhibition of glyoxalse I (S-lactoyl-glutathione methylglyoxal lyase, isomerizing; EC 4.4.1.5). The substrate of glyoxalse I (Glo I), methylglyoxal, has growth inhibitory properties. Glo I was purified 7000-fold from human red blood cells, and the concentration of various flavones was determined for 50% inhibition (I50) of enzyme activity. These compounds resemble the transition state of the methylglyoxal hemimercaptal as previously reported [Int. J. Quantum Chem. Quantum Biol. Symp., 10, 357 (1983)]. The I50 in μM varies from 5 to 330 for the flavones tested, with the parent compound 3-hydroxyflavone having an I50 of 10 μM. The most inhibitory compound in vitro was myricetin (5 μM), which has a 3′,4′,5′-trihydroxyphenolic ring at the 2 position of the pyrone ring.
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TL;DR: Results show that the chemical reaction of methyl-glyoxat with 7-methylguanosine is not the mechanism for the inhibition of protein synthesis by methylglyoxal and that methyl Glyoxat is a weak general inhibitor of translation.
Abstract: Methylglyoxal was a weak inhibitor of translation in the reticulocyte-lysate cell-free system and it did not display cap-dependent inhibition A similar inhibition was obtained in a wheat-germ cell-free system that displayed extensive cap-dependent inhibition with the cap analogue 7-methylguanosine phosphate These results show that the chemical reaction of methyl-glyoxat with 7-methylguanosine is not the mechanism for the inhibition of protein synthesis by methylglyoxal and that methylglyoxat is a weak general inhibitor of translation
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12 Nov 1984
TL;DR: In this article, an alcohol is made to react with an aqueous solution of methylglyoxal in the presence of an acidic catalyst (e.g. acidic ion exchange resin) at 50-100 deg.C without removing the produced water from the system to obtain the objective methyl glyoxal acetal.
Abstract: PURPOSE:To prepare the titled compound economically, in high yield, with a simple procedure, by reacting an aqueous solution of methylglyoxal with an alcohol in the presence of an acidic catalyst at a specific temperature, without removing produced water from the system. CONSTITUTION:An alcohol (preferably methanol) is made to react with an aqueous solution of methylglyoxal in the presence of an acidic catalyst (e.g. acidic ion exchange resin) at 50-100 deg.C, preferably 60-80 deg.C without removing the produced water from the system to obtain the objective methylglyoxal acetal of formula (R is 1-4C alkyl).
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TL;DR: The psoriatic keratinocytes appeared to be more sensitive to the action of polyamine antimetabolites, and the inhibition of DNA and protein synthesis by methylglyoxal bis (guanylhydrazone) was prevented by concomitant treatment with spermidine.
Abstract: We describe the effect of two polyamine antimetabolites on polyamine and macromolecule synthesis of cultured human keratinocytes obtained by suction blisters from normal skin and the uninvolved skin of psoriatic patients. The concentrations of spermidine and spermine steadily increased during the culture of normal keratinocytes in vitro, whereas the putrescine concentration showed only a transient rise at the beginning of the active growth phase. Treatment with difluoromethylornithine decreased the concentrations of putrescine and spermidine in both normal and uninvolved psoriatic keratinocytes, but had no effect on either DNA or protein synthesis. Methylglyoxal bis(guanylhydrazone) marginally decreased the levels of spermidine and spermine and significantly inhibited the DNA and protein synthetic activities. Pretreatment of uninvolved psoriatic keratinocytes with difluoromethylornithine enhanced the accumulation of methylglyoxal bis(guanylhydrazone), resulting in a profound inhibition of cellular macromolecule synthesis. This synergistic effect was not seen in normal keratinocytes. Thus, although no statistically significant difference was observed between the cells derived from normal and uninvolved psoriatic epidermis, the psoriatic keratinocytes appeared to be more sensitive to the action of polyamine antimetabolites. The inhibition of DNA and protein synthesis by methylglyoxal bis(guanylhydrazone) was prevented by concomitant treatment with spermidine.
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01 Jan 1984
TL;DR: In this paper, the polymorphism of the red cell enzyme glyoxalase I (GLO-I), first described by Kompf et al. using starch gel electrophoresis, was investigated by isoelectric focusing on polyacrylamide plates at pH 4-5.
Abstract: The polymorphism of the red cell enzyme glyoxalase I (GLO-I), first described by Kompf et al. [1] using starch gel electrophoresis, was investigated by isoelectric focusing (IEF) on polyacrylamide plates at pH 4-5 (LKB, PAG plates). Briefly, 20 μl red cell lysate was applied near the cathode. Following the focusing, the gels were incubated for 20 minutes at 37 °C in a 0.2 M phosphate buffer containing 257 mM methylglyoxal and 16.3 mM reduced glutathione. The detection gel consisted of 1% agarose in 0.1 M Tris buffer with 0.06 mM DCIP and 2.4 mM MTT poured on a GelBond film.
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TL;DR: The reaction ofα-ethoxyacrolein with alcohols produces the acetals of methylglyoxal in 55–65% yields.
Abstract: The reaction ofα-ethoxyacrolein with alcohols produces the acetals of methylglyoxal in 55–65% yields.
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TL;DR: In this paper, the tin(II) enediolate 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.