...Alaa Shafie; Mingzhan Xue; Paul J. Thornalley; Naila Rabbani The glyoxalase I gene GLO1 is a hotspot for copy number variation in the human and mouse genomes. The additional copies are often functional, giving rise to 2–4-fold increased glyoxalase I expression and activity. The prevalence of GLO1...

... correlation of skin and urinary pentosidine with joint damage in early-stage OA. RAGE (receptor for AGEs) is a cell-surface receptor in the synovial tissue of patients with OA and RA. The RAGE agonist S100A12 is increased in RA and OA. Activation of RAGE may decrease expression of Glo1 (glyoxalase I...

... alone cannot explain the development and progression of DN. Recently it has been shown that the endogenous reactive metabolite MG (methylglyoxal), elevated as a consequence of reduced Glo1 (glyoxalase I), can contribute to the gain of function via post-translational modification of neuronal ion channels...

...Marcel Deponte Our current knowledge of the isomerase glyoxalase I and the thioesterase glyoxalase II is based on a variety of prokaryotic and eukaryotic (model) systems with an emphasis on human glyoxalases. During the last decade, important insights on glyoxalase catalysis and structure–function...

...John F. Honek A number of bacterial glyoxalase I enzymes are maximally activated by Ni 2+ and Co 2+ ions, but are inactive in the presence of Zn 2+ , yet these enzymes will also bind this metal ion. The structure–activity relationships between these two classes of glyoxalase I serve as important...

...Makoto Arai; Naomi Nihonmatsu-Kikuchi; Masanari Itokawa; Naila Rabbani; Paul J. Thornalley Glyoxalase I catalyses the isomerization of the hemithioacetal formed non-enzymatically from methylglyoxal and glutathione to S - D -lactoylglutathione. The activity of glyoxalase I is conventionally measured...

... cells has inadvertently provided probes for the detection of dicarbonyls such as MG. We describe the application of DAF-2 (4,5-diaminofluorescein) and DAR-1 (4,5-diaminorhodamine) for the detection of MG in cell-free systems and application for high-throughput assay of glyoxalase activity and assay...

...Naila Rabbani; Paul J. Thornalley On 27–29 November 2013, researchers gathered at the University of Warwick, Coventry, U.K., to celebrate the centennial of the discovery of the glyoxalase pathway. The glyoxalase system was discovered and reported in papers by Carl Neuberg and by Henry Drysdale...

... is a primary cause of deregulated heart function. Toxic by-products of non-enzymatic glycolysis, mainly methylglyoxal, have been shown to contribute to the endothelial cell damage. Methylglyoxal is a precursor for advanced glycation end-products, and, although it is detoxified by the glyoxalase system...

... was the major quantitative adduct detected in vivo . It was linked to frequency of DNA strand breaks and increased markedly during apoptosis induced by a cell-permeant glyoxalase I inhibitor. Glyoxalase I metabolizes >99% methylglyoxal and thereby protects the proteome and genome. Gene deletion of GLO1...

... of exposure to MG is best understood in the Gram-negative bacteria. The major mechanism of protection is the spontaneous reaction of MG with GSH to form hemithiolacetal, followed by detoxification by the glyoxalase system leading to the production of d-lactate. The KefB and KefC glutathione-gated K + efflux...

...% of the glycolytic flux. We investigated methylglyoxal metabolism in Saccharomyces cerevisiae cells, using haploid null mutants. Growth studies showed that the most sensitive strains to 2-oxoaldehydes were the null mutants for GSH1 and GLO1 , coding for glutathione synthase I and glyoxalase I respectively. The GRE3...

...] derived from 3-deoxyglucosone and others. Glyoxal and methylglyoxal induce multi-base deletions, and base-pair substitutions – mostly occurring at G:C sites with G:C→C:G and G:C→T:A transversions. Suppression of nucleotide glycation by glyoxalase I and aldehyde reductases and dehydrogenases, and base...

... of enzymes that suppress the physiological levels of potent glycating agents and repair glycated proteins: glyoxalase I, aldehyde reductases and dehydrogenases, amadoriase and fructosamine 3-phosphokinase. The enzymatic defence against glycation influences morbidity and the efficiency of drug therapy...

...P.J. Thornalley Glyoxalase I is part of the glyoxalase system present in the cytosol of cells. The glyoxalase system catalyses the conversion of reactive, acyclic α-oxoaldehydes into the corresponding α-hydroxyacids. Glyoxalase I catalyses the isomerization of the hemithioacetal, formed...

... carbonyl compound (‘carbonyl stress’) and subsequent AGE formation can contribute to cross-linking of protein fibrils and to pathological pro-inflammatory signalling, which all contribute to pathological changes and dementia progression in AD. However, the human brain has developed the glyoxalase system...