title: Detection, quantification, and total synthesis of novel 3-hydroxykynurenine glucoside-derived metabolites present in human lenses.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Gad
authors.forename: Jasminka
authors.initials: J
authors.lastname: Mizdrak
authors.forename: David I
authors.initials: DI
authors.lastname: Pattison
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davies
authors.forename: Roger J W
authors.initials: RJ
authors.lastname: Truscott
authors.forename: Joanne F
authors.initials: JF
authors.lastname: Jamie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002386:Cataract / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005960:Glucosides / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D007908:Lens, Crystalline / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D010654:Phenylbutyrates / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: C402223:3-hydroxykynurenine glucoside; C444345:4-(2-amino-3-hydroxyphenyl)--4-oxobutanoic acid O-diglucoside; D005960:Glucosides; D010654:Phenylbutyrates
keywords: UV filters; age related nuclear cataract; photooxidation; tryptophan