Protein and nucleotide damage by glyoxal and methylglyoxal in physiological systems - role in ageing and disease
TLDR
It is appreciated that glyoxalase 1 protects against dicarbonyl modifications of the proteome, genome and lipome and represents part of the enzymatic defence against glycation.Abstract:
Glycation of proteins, nucleotides and basic phospholipids by glyoxal and methylglyoxal--physiological substrates of glyoxalase 1--is potentially damaging to the proteome, genome and lipidome. Glyoxalase 1 suppresses glycation by these alpha-oxoaldehyde metabolites and thereby represents part of the enzymatic defence against glycation. Albert Szent-Gyorgyi pioneered and struggled to understand the physiological function of methylglyoxal and the glyoxalase system. We now appreciate that glyoxalase 1 protects against dicarbonyl modifications of the proteome, genome and lipome. Latest research suggests there are functional modifications of this process--implying a role in cell signalling, ageing and disease.read more
Citations
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Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications
Jacek Zielonka,Joy Joseph,Adam Sikora,Micael Hardy,Olivier Ouari,Jeannette Vasquez-Vivar,Gang Cheng,Marcos Lopez,Balaraman Kalyanaraman +8 more
TL;DR: The physicochemical basis for mitochondrial accumulation of lipophilic cations, synthetic chemistry strategies to target compounds to mitochondria, mitochondrial probes, and sensors, and examples of mitochondrial targeting of bioactive compounds are described.
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Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes.
TL;DR: This comprehensive review summarizes fundamental principles of glutathione catalysis and compares the structures and mechanisms ofglutathione-dependent enzymes, including glutathion reductase, glutaredoxins, glutATHione peroxidases, peroxiredoxinases, glyoxalases 1 and 2, glutthione transferases and MAPEG.
Journal ArticleDOI
Methylglyoxal, the dark side of glycolysis
TL;DR: A main emerging concept is that these two neural cell types have different and energetically adapted glyoxalase defense mechanisms which may serve as protective mechanism against methylglyoxal-induced cellular damage.
Journal ArticleDOI
Hyperglycemia and glycation in diabetic complications.
TL;DR: The mechanism of glycation and of AGEs formation and the role of hyperglycemia, A GEs, and oxidative stress in the pathophysiology of diabetic complications are summarized.
Journal ArticleDOI
Methylglyoxal, glyoxalase 1 and the dicarbonyl proteome.
Naila Rabbani,Paul J. Thornalley +1 more
TL;DR: Glyoxalase 1 and aldo–keto reductase 1B1 metabolise >99% MG to innocuous products and thereby protect the proteome, providing an enzymatic defence against MG-mediated glycation.
References
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Protein degradation and protection against misfolded or damaged proteins
TL;DR: A full understanding of the pathogenesis of the protein-folding diseases will require greater knowledge of how misfolded proteins are recognized and selectively degraded.
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Formation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose.
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Nicole Verzijl,Jeroen DeGroot,Suzanne R. Thorpe,Ruud A. Bank,J. Nikki Shaw,Timothy J. Lyons,Johannes W. J. Bijlsma,Floris P J G Lafeber,John W. Baynes,Johan M. TeKoppele +9 more
TL;DR: First experimental evidence that protein turnover is a major determinant in AGE accumulation in different collagen types is provided, thereby providing the first reasonable estimates of the half-lives of these collagens.
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Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy
Hans-Peter Hammes,Xueliang Du,Diane Edelstein,Tetsuya Taguchi,Takeshi Matsumura,Qida Ju,Jihong Lin,Angelika Bierhaus,Peter P. Nawroth,Dieter Hannak,Michael Neumaier,Regine Bergfeld,Ida Giardino,Michael Brownlee +13 more
TL;DR: In this article, the lipid-soluble thiamine derivative benfotiamine can inhibit three major biochemical pathways simultaneously, which might be clinically useful in preventing the development and progression of diabetic complications.
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N-epsilon-(carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins.
Mahtab U. Ahmed,Elisabeth Brinkmann Frye,Thorsten P. Degenhardt,Suzanne R. Thorpe,John W. Baynes +4 more
TL;DR: Levels of CML and CEL are proposed to provide an index of glyoxal and methylglyoxal concentrations in tissues, alterations in glutathione homoeostasis and dicarbonyl metabolism in disease, and sources of advanced glycation end-products in tissue proteins in aging and disease.