Methylglyoxal, glyoxalase 1 and the dicarbonyl proteome
Top Cited Papers
- 21 October 2010
- journal article
- review article
- Published by Springer Science and Business Media LLC in Amino Acids
- Vol. 42 (4), 1133-1142
- https://doi.org/10.1007/s00726-010-0783-0
Abstract
Methylglyoxal (MG) is a potent protein glycating agent. Glycation is directed to guanidino groups of arginine residues forming mainly hydroimidazolone N δ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) residues. MG-H1 formation is damaging to the proteome as modification is often directed to functionally important arginine residues. MG-H1 content of proteins is quantified by stable isotopic dilution analysis tandem mass spectrometry and also by immunoblotting with specific monoclonal antibodies. MG-glycated proteins undergo cellular proteolysis and release MG-H1 free adduct for excretion. MG-H1 residues have been found in proteins of animals, plants, bacteria, fungi and protoctista. MG-H1 is often the major advanced glycation endproduct in proteins of tissues and body fluids, increasing in diabetes and associated vascular complications, renal failure, cirrhosis, Alzheimer’s disease, arthritis, Parkinson’s disease and ageing. 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. Proteins susceptible to MG modification with related functional impairment are called the “dicarbonyl proteome” (DCP). DCP includes albumin, haemoglobin, transcription factors, mitochondrial proteins, extracellular matrix proteins, lens crystallins and other proteins. DCP component proteins are linked to mitochondrial dysfunction in diabetes and ageing, oxidative stress, dyslipidemia, cell detachment and anoikis and apoptosis. Biochemical and physiological susceptibility of a protein to modification by MG and sensitivity of biochemical pathways and physiological systems to related functional impairment under challenge of physiologically relevant increases in MG exposure are key concepts. Improved understanding of the DCP will likely have profound importance for human health, longevity and treatment of disease.Keywords
This publication has 84 references indexed in Scilit:
- Alpha-synuclein deficiency leads to increased glyoxalase I expression and glycation stressCellular and Molecular Life Sciences, 2010
- GLO1—A novel amplified gene in human cancerGenes, Chromosomes and Cancer, 2010
- Hydroimidazolone modification of human αA-crystallin: Effect on the chaperone function and protein refolding abilityBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2010
- Hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation in rat mesenteric arteries is mediated by intracellular methylglyoxal levels in a pathway dependent on oxidative stressDiabetologia, 2010
- The molecular basis for impaired hypoxia-induced VEGF expression in diabetic tissuesProceedings of the National Academy of Sciences of the United States of America, 2009
- Dicarbonyls linked to damage in the powerhouse: glycation of mitochondrial proteins and oxidative stressBiochemical Society Transactions, 2008
- Reversal of Hyperglycemia‐Induced Angiogenesis Deficit of Human Endothelial Cells by Overexpression of Glyoxalase 1In VitroAnnals of the New York Academy of Sciences, 2008
- Decreasing Intracellular Superoxide Corrects Defective Ischemia-induced New Vessel Formation in Diabetic MicePublished by Elsevier BV ,2008
- Elimination of damaged proteins during differentiation of embryonic stem cellsProceedings of the National Academy of Sciences of the United States of America, 2006
- Prediction of post‐translational glycosylation and phosphorylation of proteins from the amino acid sequenceProteomics, 2004