Purchase this article with an account.
Stefan Rakete, Hua Wang, Mikhail Linetsky, Ram H Nagaraj; Identification of a novel fluorescent product from the reaction of 3OH-kynurenine and erythrulose: Relevance to lens aging. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5577.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Kynurenines are the oxidation product of tryptophan present in human lenses. They modify lens proteins through chemical reactions. Ascorbate is a major constituent of the lens and it is oxidized at increasing rate in aged and cataractous lenses. Ascorbate oxidation products are reactive and they are known to form advanced glycation end products in lens proteins. However, the reactions of kynurenines with ascorbate oxidation products, which could affect lens aging and cataract formation, have not been investigated so far. Here we have investigated the reaction of erythrulose, a major ascorbate oxidation product in the lens, with kynurenines.
Kynurenine, 3-hydroxykynurenine and 3-hydroxykynurenine glucoside were incubated in the presence of erythrulose at physiological conditions. The reaction mixtures were analyzed by UPLC. A major fluorescent product arising from 3-hydroxykynurenine/erythrulose incubation was isolated and characterized by mass spectrometry and NMR. As a model compound for 3-hydroxykynurenine 1-(2-amino-3-hydroxyphenyl)ethanone was incubated in the same manner as kynurenines.
The reaction of 3-hydroxykynurenine with erythrulose is remarkably rapid and resulted in the formation of a major fluorescent product. The highest yield of this fluorescent product was observed between pH 4 and 5 but substantial amounts were also observed at neutral pH. Neither kynurenine nor 3-hydroxykynurenine glucoside generated this product. As only 3-hydroxykynurenine but not 3-hydroxykynurenine glucoside generated the product from the reaction with erythrulose, we thought that the aminophenol functionality was essential for the formation of the product. This was confirmed by using 1-(2-amino-3-hydroxyphenyl)ethanone as a model compound in the place of 3-hydroxykynurenine; the reaction rapidly produced a fluorescent compound, structure of which is shown below. Based on these results, we excluded the participation of the α-amino group for the formation of the product.
Due to the rapid conversion of 3-hydroxykynurenine to the new compound, this reaction is likely to occur in the lens and the product generated could further react with lens proteins to form a fluorescent adduct and function as a photosensitizer in lens proteins.
This PDF is available to Subscribers Only