Protein and nucleotide damage by glyoxal and methylglyoxal in physiological systems--role in ageing and disease.
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-Györgyi 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.
Protein Damage and Systems Biology Research Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, University Hospital, Coventry, UK. P.J.Thornalley@warwick.ac.uk
Paul J
PJ
Thornalley
D000375:Aging / Q000502:physiology*; D000818:Animals; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006037:Glyoxal / Q000378:metabolism*; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000502:physiology; D009711:Nucleotides / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000378:metabolism; D013869:Thiolester Hydrolases / Q000502:physiology; D000099301:Hydroxyacylglutathione Hydrolase
D017127:Glycation End Products, Advanced; D006037:Glyoxal; D007791:Lactoylglutathione Lyase; D009711:Nucleotides; D011506:Proteins; D011765:Pyruvaldehyde; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase