Oxidative glycation and free radical production: a causal mechanism of diabetic complications.
Glucose may oxidise under physiological conditions and lead to the production of protein reactive ketoaldehydes, hydrogen peroxide and highly reactive oxidants. Glucose is thus able to modify proteins by the attachment of its oxidation derived aldehydes, leading to the development of novel protein fluorophores, as well as fragment protein via free radical mechanisms. The fragmentation of protein by glucose is inhibitable by metal chelators such as diethylenetriamine pentaacetic acid (DETAPAC) and free radical scavengers such as benzoic acid, and sorbitol. The enzymic antioxidant, catalase, also inhibits protein fragmentation. Protein glycation and protein oxidation are inextricably linked. Indeed, using boronate affinity chromatography to separate glycated from non-glycated material, we demonstrate that proteins which are glycated exhibit an enhanced tryptophan oxidation. Our observation that both glycation and oxidation occur simultaneously further supports the hypothesis that tissue damage associated with diabetes and ageing has an oxidative origin.
Hunt
J V
JV
Department of Clinical Pharmacology, University College London.
Wolff
S P
SP
D000375:Aging / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D019817:Benzoic Acid; D002417:Cattle; D002614:Chelating Agents / Q000494:pharmacology; D002846:Chromatography, Affinity; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism; D016166:Free Radical Scavengers; D005609:Free Radicals; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D010084:Oxidation-Reduction; D004369:Pentetic Acid / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D013012:Sorbitol / Q000494:pharmacology
D000447:Aldehydes; D001565:Benzoates; D002614:Chelating Agents; D016166:Free Radical Scavengers; D005609:Free Radicals; D006878:Hydroxides; D011506:Proteins; D017665:Hydroxyl Radical; D013012:Sorbitol; D004369:Pentetic Acid; D019817:Benzoic Acid; D006861:Hydrogen Peroxide; D005947:Glucose