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

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.