title: Fructose induced deactivation of antioxidant enzymes: preventive effect of pyruvate.
abstract: Glycation initiated changes in tissue proteins, which are triggered by the Schiff base formation between the sugar carbonyl and the protein -NH2, have been suggested to play an important role in the development of diabetes-related pathological changes such as the formation of cataracts. While the initial reaction takes place by the interaction of >C=O of the parent sugars with the -NH2 of proteins, reactive oxygen species (ROS) dependent generation of more reactive dicarbonyl derivatives from the oxidation of sugars also plays a significant role in these changes, altering the structural as well as functional properties of proteins. The purpose of this study was to examine whether the activities of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), catalase and superoxide dismutase (SOD) could be affected by the high levels of fructose prevalent in diabetic lenses. Incubation of the enzymes with this sugar led to a significant loss of their activities. GAPDH was inactivated within a day. This was followed by the inactivation of catalase (3-4 days) and SOD (6 days). The loss of the activities was prevented significantly by incorporation of pyruvate in the incubation mixture. The protective effect is ascribable to its ability to competitively inhibit glycation as well as to its ROS scavenging activity. Hence, it could play a significant role in the maintenance of lens physiology and cataract prevention.
authors.affiliation: Department of Ophthalmology, School of Medicine, University of Maryland, Baltimore 21201, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zhao
authors.forename: P S
authors.initials: PS
authors.lastname: Devamanoharan
authors.forename: S D
authors.initials: SD
authors.lastname: Varma
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005632:Fructose / Q000494:pharmacology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors*; D006031:Glycosylation; D066298:In Vitro Techniques; D019289:Pyruvic Acid / Q000494:pharmacology*; D011817:Rabbits; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors*
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D005632:Fructose; D019289:Pyruvic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases