Title

Detection, quantification, and total synthesis of novel 3-hydroxykynurenine glucoside-derived metabolites present in human lenses

RIS ID

88009

Publication Details

Gad, N. A., Mizdrak, J., Pattison, D. I., Davies, M. J., Truscott, R. J. W. & Jamie, J. F. (2014). Detection, quantification, and total synthesis of novel 3-hydroxykynurenine glucoside-derived metabolites present in human lenses. Investigative Ophthalmology and Visual Science, 55 (2), 849-855.

Abstract

Purpose. 3-Hydroxykynurenine O-β-D-glucoside (3OHKG) protects the lens from UV damage, and novel related species may act analogously. The aim of this study was to detect, quantify, and elucidate the structures of novel 3-hydroxykynurenine glucoside–derived metabolites present in the human lens.

Methods. Compounds were detected and quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in 24 human lenses of different ages, of which 22 were normal and two had cataract. Structures of these were confirmed through total synthesis.

Results. 3OHKG concentrations decreased with age in the lens nuclei, whereas the levels of three novel species, 4-(2-amino-3-hydroxyphenyl)-2-hydroxy-4-oxobutanoic acid O-β-D-glucoside (3OHKG-W), 3-hydroxykynurenine O-β-D-glucoside yellow (3OHKG-Y), and 2-amino-3-hydroxyacetophenone O-β-D-glucoside (AHAG), increased, though to different extents. In contrast, the concentrations present in the cortex of the lens remained constant with age.

Conclusions. Three novel 3OHKG-derived metabolites have been detected in extracts from human lenses.

Grant Number

NHMRC/1008667

Grant Number

ARC/CE0561607

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