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Proteins Susceptible to Dicarbonyl Glycation at Functional Sites in Health, Aging, and Disease
a Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV2 2DX, United Kingdom
Key Words: glycation • glyoxal • methylglyoxal • glyoxalase • arginine • hydroimidazolone • bioinformatics
Address for correspondence: Naila Rabbani, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV2 2DX, UK. Voice: +44-24 7696 8593; fax: +44-24 7696 8595. N.Rabbani{at}warwick.ac.uk
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 1 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.
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