Glycation-induced inactivation of aspartate aminotransferase, effect of uric acid.
Glycation is common posttranslational modification of proteins impairing their function, which occurs during diabetes mellitus and aging. Beside extracellular glycation of long-lived proteins, intracellular modifications of short-lived proteins by more reactive sugars like fructose are possible. The process includes free oxygen radicals (glycoxidation). In an attempt to reduce glycoxidation and formation of advanced glycation products (AGE), influence of 0.2-1.2 mM uric acid as endogenous antioxidant on glycoxidation of purified pig heart aspartate aminotransferase (AST) by 50 mM and 500 mM D-fructose in vitro was studied. Uric acid at 1.2 mM concentration reduced AST activity decrease and formation of total AGE products caused by incubation in vitro of the enzyme with sugar up to 25 days at 37 degrees C. The results thus support the hypothesis that uric acid has beneficial effects in controlling protein glycoxidation. The in vitro system AST-fructose proved to be a useful tool for investigation of glycation process.
Bousová
Iva
I
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University in Prague, Czech Republic. bousova@faf.cuni.cz
Bakala
Hilaire
H
Chudácek
Robert
R
Palicka
Vladimír
V
Drsata
Jaroslav
J
D001219:Aspartate Aminotransferases / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D013997:Time Factors; D014527:Uric Acid / Q000378:metabolism / Q000494:pharmacology*
D017127:Glycation End Products, Advanced; D014527:Uric Acid; D005632:Fructose; D001219:Aspartate Aminotransferases