Detection, quantification, and total synthesis of novel 3-hydroxykynurenine glucoside-derived metabolites present in human lenses
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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 Jonathan; Truscott, Roger J W; Jamie, Joanne F.
In: Investigative Ophthalmology & Visual Science, Vol. 55, No. 2, 02.2014, p. 849-55.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
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 Jonathan
AU - Truscott, Roger J W
AU - Jamie, Joanne F
PY - 2014/2
Y1 - 2014/2
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.
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Cataract
KW - Chromatography, High Pressure Liquid
KW - Glucosides
KW - Humans
KW - Lens, Crystalline
KW - Magnetic Resonance Spectroscopy
KW - Middle Aged
KW - Phenylbutyrates
KW - Spectrophotometry, Ultraviolet
KW - Tandem Mass Spectrometry
KW - Young Adult
U2 - 10.1167/iovs.13-13464
DO - 10.1167/iovs.13-13464
M3 - Journal article
C2 - 24408982
VL - 55
SP - 849
EP - 855
JO - Investigative Ophthalmology & Visual Science
JF - Investigative Ophthalmology & Visual Science
SN - 0146-0404
IS - 2
ER -
ID: 128973954