Topic
Methylglyoxal
About: Methylglyoxal is a research topic. Over the lifetime, 2844 publications have been published within this topic receiving 102037 citations. The topic is also known as: acetylformaldehyde & pyruvaldehyde.
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TL;DR: The first structural study of the lowest triplet states of three α-dicarbonyls (glyoxal, methyl glyoxal and biacetyl) using the technique of laser-induced phosphorescence (LIP) spectroscopy in supersonic jets was performed in this article.
Abstract: We report the first structural study of the lowest triplet states of three α‐dicarbonyls (glyoxal, methylglyoxal, and biacetyl) using the technique of laser‐induced phosphorescence (LIP) spectroscopy in supersonic jets. At the level of vibrational resolution, 3Au glyoxal appears to have a geometry very similar to that of the ground state. But the T1←S0 transitions of methylglyoxal and biacetyl each exhibit strong progressions in the torsional vibrations of the methyl groups, showing that these molecules undergo a conformational change on excitation to the lowest triplet state. A Franck–Condon analysis of the methylglyoxal spectrum, with proper consideration for nuclear spin statistics, yields a methyl barrier of V3=115±5 cm−1 in this state. This value has been confirmed by a direct measurement of the tunneling splitting of A and E torsional levels. The hindering potential in the lowest triplet state of methylglyoxal is substantially different from those in the ground (V3=269 cm−1) and first excited single...
78 citations
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TL;DR: The synergism between the action of the two compounds was based upon a unique drug interaction; a preceding treatment with difluoromethyl ornithine greatly increased the uptake of subsequently administered methylglyoxal bis‐(guanylhydrazone) as verified by the actual determinations of the latter drug in the circulating leukemia cells.
Abstract: Sequential administration of alpha-difluoromethyl ornithine and methylglyoxal bis(guanylhydrazone), two differently acting inhibitors of the biosynthesis of natural polyamines, produced a rapid and distinct therapeutic response in four children with advanced lymphoblastic and in one with myeloblastic leukemia. The synergism between the action of the two compounds was based upon a unique drug interaction; a preceding treatment with difluoromethyl ornithine greatly increased the uptake of subsequently administered methylglyoxal bis(guanylhydrazone) as verified by the actual determinations of the latter drug in the circulating leukemia cells. The side-effects associated with the combined drug regiment were either absent or mild.
78 citations
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TL;DR: Evidence is presented that the conversion of methylglyoxal to pyruvate was direct and did not involve its preliminary conversion to lactate, and the name α-keto aldehyde dehydrogenase is suggested.
78 citations
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TL;DR: Using Saccharomyces cerevisiae cells with different glycation phenotypes and MALDI‐TOF peptide mass fingerprints, enolase’2 is identified as the primary methylglyoxal glycation target in yeast and two other glycolytic enzymes are also glycated, aldolase and phosphoglycerate mutase.
Abstract: Protein glycation by methylglyoxal is a nonenzymatic post-translational modification whereby arginine and lysine side chains form a chemically heterogeneous group of advanced glycation end-products. Methylglyoxal-derived advanced glycation end-products are involved in pathologies such as diabetes and neurodegenerative diseases of the amyloid type. As methylglyoxal is produced nonenzymatically from dihydroxyacetone phosphate and d-glyceraldehyde 3-phosphate during glycolysis, its formation occurs in all living cells. Understanding methylglyoxal glycation in model systems will provide important clues regarding glycation prevention in higher organisms in the context of widespread human diseases. Using Saccharomyces cerevisiae cells with different glycation phenotypes and MALDI-TOF peptide mass fingerprints, we identified enolase 2 as the primary methylglyoxal glycation target in yeast. Two other glycolytic enzymes are also glycated, aldolase and phosphoglycerate mutase. Despite enolase's activity loss, in a glycation-dependent way, glycolytic flux and glycerol production remained unchanged. None of these enzymes has any effect on glycolytic flux, as evaluated by sensitivity analysis, showing that yeast glycolysis is a very robust metabolic pathway. Three heat shock proteins are also glycated, Hsp71/72 and Hsp26. For all glycated proteins, the nature and molecular location of some advanced glycation end-products were determined by MALDI-TOF. Yeast cells experienced selective pressure towards efficient use of d-glucose, with high methylglyoxal formation as a side effect. Glycation is a fact of life for these cells, and some glycolytic enzymes could be deployed to contain methylglyoxal that evades its enzymatic catabolism. Heat shock proteins may be involved in proteolytic processing (Hsp71/72) or protein salvaging (Hsp26).
78 citations
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TL;DR: Although extents of modification are usually low, the dicarbonyl proteome is a critical feature of the impact of glycation on physiological function—particularly in mitochondrial dysfunction, vascular disease, and potentially in disorders of lipoprotein metabolism.
Abstract: Reactive, physiological, dicarbonyl, glycating agents, glyoxal and methylglyoxal, are arginine-directed glycating agents forming mainly hydroimidazolone residues. Arginine residues have high-frequency occurrence in sites of protein-protein, enzyme substrate and protein-nucleotide binding sites. There is emerging evidence that functionally important arginine residues in proteins are often activated toward dicarbonyl glycation-leading to functional impairment. When uncontrolled, this is associated with aging, degenerative diseases, and metabolic disorders where dicarbonyl glycation may be viewed as damage to the proteome. The glyoxalase system, particularly glyoxalase 1, is the vanguard against dicarbonyl glycation in physiological systems. Functional regulation of glyoxalase I suggests a role for dicarbonyl glycation in cell signaling. Although extents of modification are usually low, the dicarbonyl proteome is a critical feature of the impact of glycation on physiological function-particularly in mitochondrial dysfunction, vascular disease, and potentially in disorders of lipoprotein metabolism.
78 citations