Glycation-induced inactivation of aspartate aminotransferase, effect of uric acid

Abstract

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.

Fructose-induced modifications of myoglobin: Change of structure from met (Fe3+) to oxy (Fe2+) form

“…Several proteins namely hemoglobin [14][15][16], crystallins [33], glyceraldehydes 3-phosphate dehydrogenase, catalase, superoxide dismutase [34], albumin [35] and aspartate amino transferase [36] have been reported to be the targets of fructose modification. Although glycation of Mb has been reported from our laboratory [8,9], there has been no study on its fructation.…”

Cyperus rotundus suppresses AGE formation and protein oxidation in a model of fructose-mediated protein glycoxidation

“…Reactive oxygen species (ROS) such as O 2 •− , H 2 O 2 , and • OH may contribute to these reactions, which require trace levels of catalytic redox-active transition metal ions. The process includes also oxidative steps and is therefore called glycoxidation [6][7][8]. Regarding the significance of glycoxidative stress to diabetic pathology, a supplement of antioxidants to inhibit the process of protein modification appears to be a good strategy for preventing diabetic complications [9].…”

A distinct metabolic signature predicts development of fasting plasma glucose

“…The aspartate aminotransferase was reported to be associated with glucose metabolism and insulin resistance [38]. Bousova et al reported reduced aspartate amino transferase activity induced by fructose and the resulting glycation in vitro and observed beneficial effects of uric acid in that context [55]. Hageman et al reported that feeding an aspartate rich protein blend decreased the postprandial glucose response in rats [56].…”