Showing papers on "Methylglyoxal published in 1973"

Effect of methylglyoxal bis(guanylhydrazone) on polyamine metabolism in normal and regenerating rat liver and rat thymus.

Abstract: 1. Injections of sublethal doses of methylglyoxal bis(guanylhydrazone), a potent inhibitor of putrescine-activated S-adenosylmethionine decarboxylase in vitro, resulted after a few days in an immense increase in the activity of S-adenosylmethionine decarboxylase in normal and regenerating rat liver and in rat thymus. The increase in the activity of S-adenosylmethionine decarboxylase was at least partly due to a marked lengthening of the half-life of the enzyme. 2. In regenerating liver and thymus there was also a moderate stimulation of the activity of ornithine decarboxylase (EC 4.1.1.17) and a marked accumulation of tissue putrescine. 3. Injection of methylglyoxal bis(guanylhydrazone) into the rat also markedly decreased the activity of diamine oxidase (EC 1.4.3.6) in thymus. 4. In no cases where doses of methylglyoxal bis(guanylhydrazone) close to the LD(50) dose for the rat were used was it possible to lower tissue spermidine content to any significant extent. 5. Methylglyoxal bis(guanylhydrazone) seemed to act as a competitive inhibitor for the substrate S-adenosylmethionine and as an uncompetitive inhibitor for the activator putrescine in the decarboxylation of S-adenosylmethionine in vitro. 6. In the diamine oxidase reaction, with putrescine as the substrate, methylglyoxal bis(guanylhydrazone) was a non-competitive inhibitor for putrescine.

Inhibition of spermidine formation in rat liver and kidney by methylglyoxal bis(guanylhydrazone)

Abstract: The effect of methylglyoxal bis(guanylhydrazone), a substance known to inhibit putrescine-dependent S-adenosyl-l-methionine decarboxylase, on polyamine metabolism in liver and kidney was investigated. Almost complete inhibition of the incorporation of putrescine into spermidine was obtained up to 8h after administration of 80mg of methylglyoxal bis(guanylhydrazone)/kg body wt. by intraperitoneal injection. However, by 20h after administration of the inhibitor spermidine synthesis was resumed. Considerable accumulation of putrescine occurred during this period (up to 3 times control concentrations in both tissues), but there was only a slight fall in the spermidine content. These results suggest that the putrescine-activated S-adenosyl-l-methionine decarboxylase plays an essential role in spermidine biosynthesis in rat liver and kidney, and the possibility of using methylglyoxal bis(guanylhydrazone) to study the role of polyamine synthesis in growth is discussed.

The Steady-State Kinetics of Glyoxalase I from Porcine Erythrocytes Evidence for a Random-Pathway Mechanism Involving One- and Two-Substrate Branches

Abstract: The steady-state kinetics of glyoxalase I from porcine erythrocytes were subjected to a detailed investigation. Three chemical species, methylglyoxal, glutathione, and their hemimercaptal adduct, are in equilibrium and the concentrations of these components were varied over a wide range to evaluate their influence on the velocity of the glyoxalase-I-catalyzed reaction. The experimental data were fitted by nonlinear regression methods to a number of alternative mathematical models, corresponding to possible enzymatic mechanisms, and the discrimination between the rival models was based on statistical criteria. The selection of the best model was supported by a procedure of weighting for discrimination and by examination of subsets of experimental data. The best model is interpreted as a random pathway mechanism composed of a two substrate branch involving the hemimercaptal.

Stimulation of ornithine decarboxylase activity and inhibition of S-adenosyl-L-methionine decarboxylase activity in leukaemic mice by methylglyoxal bis(guanylhydrazone).

Abstract: Administration of methylglyoxal bis(guanylhydrazone) to leukaemic mice results in an early depression followed by a marked elevation of S-adenosyl-l-methionine decarboxylase activity. Further, there is an early prolonged increase in the activity of ornithine decarboxylase, the initial enzyme in the polyamine biosynthetic pathway. Because of the profound effects of methylglyoxal bis(guanylhydrazone) in vivo on the polyamine biosynthetic pathway, the drug can no longer be considered a specific inhibitor of spermidine synthesis.

Accumulation of Methylglyoxal in a Mutant of Escherichia coli Constitutive for Gluconate Catabolism

Abstract: A culture of a mutant of Escherichia coli, derepressed for gluconate catabolism, is killed by the addition of gluconate to the culture. The product responsible for this bactericidal effect was identified as methylglyoxal. Two types of mutants resistant to gluconate were isolated. One of them showed increased activity of glyoxalase I.

Polarographic reduction of arylhydrazones of methylglyoxal, diketobutyric acid and ethyl diketobutyrate in dimethylformamide

Abstract: 1. Employing classical and cyclic polarography, and polarography with a Kalousek switch, a study was made of the electrochemical reduction of some phenyl-substituted arhylhydrazones of methylglyoxal, diketobutyric acid and its ethyl ester in dimethylformamide. 2. The nitro derivatives of the arylhydrazones form the most stable anion-radicals. 3. It is postulated that an intramolecular hydrogen bond is present in theo-nitro-substituted arylhydrazones, which is formed by the hydrazone proton and the nitro group.