title: The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases.
abstract: The formation and accumulation of advanced glycation endproducts (AGEs) are related to diabetes and other age-related diseases. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is the major precursor in the formation of AGEs. MGO is mainly formed as a byproduct of glycolysis. Under physiological circumstances, MGO is detoxified by the glyoxalase system into D-lactate, with glyoxalase I (GLO1) as the key enzyme in the anti-glycation defence. New insights indicate that increased levels of MGO and the major MGO-derived AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1), and dysfunctioning of the glyoxalase system are linked to several age-related health problems, such as diabetes, cardiovascular disease, cancer and disorders of the central nervous system. The present review summarizes the mechanisms through which MGO is formed, its detoxification by the glyoxalase system and its effect on biochemical pathways in relation to the development of age-related diseases. Although several scavengers of MGO have been developed over the years, therapies to treat MGO-associated complications are not yet available for application in clinical practice. Small bioactive inducers of GLO1 can potentially form the basis for new treatment strategies for age-related disorders in which MGO plays a pivotal role.
authors.affiliation: *Department of Internal Medicine, CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Peter Debeyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.
authors.forename: Dionne E M
authors.initials: DE
authors.lastname: Maessen
authors.affiliation: *Department of Internal Medicine, CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Peter Debeyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.affiliation: *Department of Internal Medicine, CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Peter Debeyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
mesh_terms: D002318:Cardiovascular Diseases / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D048909:Diabetes Complications / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000378:metabolism; D016166:Free Radical Scavengers / Q000627:therapeutic use; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism; D011765:Pyruvaldehyde / Q000378:metabolism*
chemical_list: D016166:Free Radical Scavengers; D017127:Glycation End Products, Advanced; D011765:Pyruvaldehyde; D004247:DNA; D007791:Lactoylglutathione Lyase