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O.K. Argirov, B. Lin, B.J. Ortwerth; HP-Lysine - A New Advanced Glycation Endproduct in Cataractous and Aged Human Lenses . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2346.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Posttranslational modifications of proteins take place during the aging of human lens. The present study describes a newly isolated glycation product of lysine which was found in cataractous and aged human lenses. Methods: Cataractous and aged human lenses were hydrolyzed and fractionated using preparative reverse-phase and ion-exchange HPLC. One of the nonproteinogenic amino acid components of hydrolysates was identified as a 3-hydroxypyridinium derivative of lysine: 2-ammonio-6-(3-oxidopyridinium-1-yl)hexanoate (HP-lysine). The compound was synthesized independently from 3-hydroxypyridine and methyl 2-[(tert-butoxycarbonyl)amino]-6-iodohexanoate. Boc-Lys was incubated at 37 oC and pH 7 with glucose, fructose, xylose, erythrulose, threose, glyceraldehyde, glycolaldehyde, ascorbate, dehydroascobic acid and methylglyoxal as well as with a mixture of glycolaldehyde and glyceraldehyde-3-phosphate. Results: The spectral and chromatographic properties of the synthetic HP-lysine and the substances isolated from hydrolyzed lenses were identical. This is a strong confirmation that HP-lysine exists in vivo. HPLC analysis showed that the amounts of HP-lysine were higher in water-insoluble compared to water-soluble proteins and were higher in cataractous lenses compared to normal aged lenses. The model incubations showed that none the carbohydrates listed above can produce HP-lysine alone. On the other hand the reaction mixture of Boc-Lys with glycolaldehyde and glyceraldehyde-3-phosphate contained the Boc derivative of HP-lysine. The irradiation of HP-lysine with UVA under anaerobic conditions and in presence of ascorbate led to formation of dehydroascorbic acid which is a highly reactive carbonyl compound. Conclusions: HP-lysine is a newly identified glycation product of lysine in the lens. It is a marker of aging and pathology of the lens and could be considered as a possible risk-factor based on its chemical and photochemical properties. The model experiments argue that HP-lysine could be formed in vivo as a result of combined interaction of glycolaldehyde and glyceraldehyde-3 phosphate with lysine residues in lens proteins. View OriginalDownload SlideView OriginalDownload Slide
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