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Journal ArticleDOI

Interaction of aldehydes with glyoxalase I and the status of several aldehyde metabolizing enzymes of Ehrlich ascites carcinoma cells.

TL;DR: The results indicate that D, and L-lactaldehyde are strong non-competitive inhibitors of glyoxalase I and the effect with the D-isomer is more pronounced, whereas both D,L-glyceraldehyde and acetaldehyde are moderately inhibitory and the nature of inhibition is strictly competitive.
Abstract: The possible effect of several physiologically important aldehydes has been tested on partially purified glyoxalase I of Ehrlich ascites carcinoma (EAC) cells. The results indicate that D, and L-lactaldehyde are strong non-competitive inhibitors of glyoxalase I and the effect with the D-isomer is more pronounced, whereas both D,L-glyceraldehyde and acetaldehyde are moderately inhibitory and the nature of inhibition is strictly competitive. Moreover, D,L-glyceraldehyde strongly inhibits the utilization of methylglyoxal by intact EAC cells. A search for the presence of several aldehyde metabolizing enzymes in EAC cells indicates that non-specific aldehyde reductase, methylglyoxal reductase, aldehyde dehydrogenase and alcohol dehydrogenase are apparently absent in this rapidly growing, highly de-differentiated malignant cell.
Citations
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Journal ArticleDOI
TL;DR: The human health risks from clinical and animal research studies are reviewed, including aldehydes as haptens in allergenic hypersensitivity diseases, respiratory allergies, and idiosyncratic drug toxicity; the potential carcinogenic risks of the carbonyl body burden.
Abstract: Aldehydes are organic compounds that are widespread in nature. They can be formed endogenously by lipid peroxidation (LPO), carbohydrate or metabolism ascorbate autoxidation, amine oxidases, cytochrome P-450s, or myeloperoxidase-catalyzed metabolic activation. This review compares the reactivity of many aldehydes towards biomolecules particularly macromolecules. Furthermore, it includes not only aldehydes of environmental or occupational concerns but also dietary aldehydes and aldehydes formed endogenously by intermediary metabolism. Drugs that are aldehydes or form reactive aldehyde metabolites that cause side-effect toxicity are also included. The effects of these aldehydes on biological function, their contribution to human diseases, and the role of nucleic acid and protein carbonylation/oxidation in mutagenicity and cytotoxicity mechanisms, respectively, as well as carbonyl signal transduction and gene expression, are reviewed. Aldehyde metabolic activation and detoxication by metabolizing enzymes are also reviewed, as well as the toxicological and anticancer therapeutic effects of metabolizing enzyme inhibitors. The human health risks from clinical and animal research studies are reviewed, including aldehydes as haptens in allergenic hypersensitivity diseases, respiratory allergies, and idiosyncratic drug toxicity; the potential carcinogenic risks of the carbonyl body burden; and the toxic effects of aldehydes in liver disease, embryo toxicity/teratogenicity, diabetes/hypertension, sclerosing peritonitis, cerebral ischemia/neurodegenerative diseases, and other aging-associated diseases.

608 citations


Cites background from "Interaction of aldehydes with glyox..."

  • ...Methylglyoxal is tumoricidal and inhibits glycolysis and mitochondrial respiration of Ehrlich ascites tumor cells, probably because of their low GLO I and GLO II levels and very low AKR enzyme activities (Biswas et al., 1996)....

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References
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Journal ArticleDOI
TL;DR: In the presence of lactaldehyde, a catabolite of MG, the inhibitory effect of MG on the respiration of tumor cells was significantly reduced and lactaldehyde can exert a similar protective effect on the loss of viability and transplantability of MG‐treated EAC cells.
Abstract: The effect of methylglyoxal (MG), ascorbic acid and lactaldehyde has been tested on the in vitro respiration of Ehrlich ascites carcinoma (EAC) cells and several normal and malignant human tissues. Methylglyoxal inhibited the respiration of each type of malignant cell and tissue tested, but it had practically no inhibitory effect on the respiration of any of the normal cells and tissues. Ascorbic acid exhibited a synergistic effect with MG in inhibiting the respiration of all the neoplastic cells. In the presence of lactaldehyde, a catabolite of MG, the inhibitory effect of MG on the respiration of tumor cells was significantly reduced. Lactaldehyde can exert a similar protective effect on the loss of viability and transplantability of MG-treated EAC cells.

41 citations


"Interaction of aldehydes with glyox..." refers background in this paper

  • ...Laetaldehyde can significantly protect the respiratory ability of various intact malignant cells [8] and also ofmitochondria of EAC cells [ 10] against the inhibitory effect of methylglyoxal....

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  • ...The work described in the present and in our previous papers have indicated that lactaldehyde may play a crucial role in the manifestation of the anticancer effect of methylglyoxal [8, 10]....

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  • ...Interestingly, lactaldehyde is a protective agent against the action of methylglyoxal on intact tumor cells [8] and on mitochondria isolated from these cells [10]....

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  • ...On the other hand, recent work from our laboratory has indicated that methylglyoxal is also tumoricidal [8]....

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  • ...Of all these aldehydes tested lactaldehyde has been found to be the most powerful inhibitor_ As previously reported from our laboratory lactaldehyde can significantly influence the antitumor effect of methylglyoxal [8, 10]....

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Journal ArticleDOI
TL;DR: It is shown that both log and stationary phase promastigotes of L. donovani can catabolize methylglyoxal to D-lactate as the major end product, and the specific activity of methyl glyoxal reductase was found to be the highest of all the catabolic enzymes.

26 citations

Book ChapterDOI
TL;DR: This chapter describes the assay method, the purification procedure, and the properties of glyoxalase I from mouse liver, which is based upon the increase in absorbance at 240 nm because of the formation of S-D-lactoylglutathione.
Abstract: Publisher Summary This chapter describes the assay method, the purification procedure, and the properties of glyoxalase I from mouse liver. The method is based upon the increase in absorbance at 240 nm because of the formation of S-D-lactoylglutathione. The purification procedure involves column material preparation, crude preparation, ethylamine-Sepharose 4B hydrophobic chromatography, and S-octylglutathione-Sepharose 4B affinity chromatography. Glyoxalase I from mouse liver has a molecular weight of 43,000; it is a dimer and is composed of identical subunits of molecular weights approximating 21,500. The purified enzyme exhibits a specific activity of 944 IU per milligram of protein employing the routine enzyme assay system. When the enzyme is stored at –30 ° C in the presence of glutathione, no significant loss of activity is observed for at least six months. There have been reports on some glyoxalase I inhibitors that are not substrate analogs; both competitive and noncompetitive inhibitions have been observed.

24 citations

Book ChapterDOI
TL;DR: The assay method, the purification procedure, and the properties of glyoxalase I isolated from human erythrocytes are described, which appears homogeneous as judged by various analytical procedures, except for the presence of the three isozymes.
Abstract: Publisher Summary Glyoxalase I catalyzes the formation of S-2-hydroxyacylglutathione from 2-oxoaldehydes, such as methylglyoxal and glutathione (GSH). This chapter describes the assay method, the purification procedure, and the properties of glyoxalase I isolated from human erythrocytes. Human glyoxalase I exists in the form of three isozymes that appear identical in their functional properties. The increase in absorbance at 240 nm because of thiolester formation from glutathione (GSH) and methylglyoxal is monitored spectrophotometrically. The purification procedure involves denaturation of hemoglobin, acetone fractionation, ammonium sulfate fractionation, affinity chromatography (I) on S-Hexylglutathione-Sepharose 6B, chromatography on Sephadex G-75, affinity chromatography II, chromatography on diethylaminoethyl (DEAE)-Sepharose, and separation of isozymes of glyoxalase I. The enzyme obtained by this procedure appears homogeneous as judged by various analytical procedures, except for the presence of the three isozymes. The enzyme is composed of two subunits of equal weight and contains one Zn per subunit that is essential to catalytic activity.

22 citations

Journal ArticleDOI
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.

10 citations