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

Nicholas A. Gad, Jasminka Mizdrak, David I. Pattison, Michael J. Davies, Roger J W Truscott, Joanne F. Jamie

Research output: Contribution to journalArticleResearchpeer-review

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.

LanguageEnglish
Pages849-855
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume55
Issue number2
DOIs
Publication statusPublished - 9 Jan 2014

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Lenses
Glucosides
Tandem Mass Spectrometry
Liquid Chromatography
Cataract
3-hydroxykynurenine glucoside
Acids
3-hydroxykynurenine

Cite this

Gad, Nicholas A. ; Mizdrak, Jasminka ; Pattison, David I. ; Davies, Michael J. ; Truscott, Roger J W ; Jamie, Joanne F. / Detection, quantification, and total synthesis of novel 3-hydroxykynurenine glucoside-derived metabolites present in human lenses. In: Investigative Ophthalmology and Visual Science. 2014 ; Vol. 55, No. 2. pp. 849-855.
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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.",
author = "Gad, {Nicholas A.} and Jasminka Mizdrak and Pattison, {David I.} and Davies, {Michael J.} and Truscott, {Roger J W} and Jamie, {Joanne F.}",
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Detection, quantification, and total synthesis of novel 3-hydroxykynurenine glucoside-derived metabolites present in human lenses. / Gad, Nicholas A.; Mizdrak, Jasminka; Pattison, David I.; Davies, Michael J.; Truscott, Roger J W; Jamie, Joanne F.

In: Investigative Ophthalmology and Visual Science, Vol. 55, No. 2, 09.01.2014, p. 849-855.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Detection, quantification, and total synthesis of novel 3-hydroxykynurenine glucoside-derived metabolites present in human lenses

AU - Gad, Nicholas A.

AU - Mizdrak, Jasminka

AU - Pattison, David I.

AU - Davies, Michael J.

AU - Truscott, Roger J W

AU - Jamie, Joanne F.

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N2 - 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.

AB - 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.

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