Novel protein modification by kynurenine in human lenses.
It is known that human lenses increase in color and fluorescence with age, but the molecular basis for this is not well understood. We demonstrate here that proteins isolated from human lenses contain significant levels of the UV filter kynurenine covalently bound to histidine and lysine residues. Identification was confirmed by synthesis of the kynurenine amino acid adducts and comparison of the chromatographic retention times and mass spectra of these authentic standards with those of corresponding adducts isolated from human lenses following acid hydrolysis. Using calf lens proteins as a model, covalent binding of kynurenine to lens proteins has been shown to proceed via side chain deamination in a manner analogous to that observed for the related UV filter, 3-hydroxykynurenine O-beta-D-glucoside. Levels of histidylkynurenine and lysylkynurenine were low in human lenses in subjects younger than 30, but thereafter increased in concentration with the age of the individual. Post-translational modification of lens proteins by tryptophan metabolites therefore appears to be responsible, at least in part, for the age-dependent increase in coloration and fluorescence of the human lens, and this process may also be important in other tissues in which up-regulation of tryptophan catabolism occurs.
Vazquez
Santiago
S
Australian Cataract Research Foundation and Department of Chemistry, University of Wollongong, New South Wales 2522, Australia.
Aquilina
J Andrew
JA
Jamie
Joanne F
JF
Sheil
Margaret M
MM
Truscott
Roger J W
RJ
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000737:chemistry* / Q000494:pharmacology; D007908:Lens, Crystalline / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008875:Middle Aged; D008956:Models, Chemical; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D014466:Ultraviolet Rays; D015854:Up-Regulation
D005960:Glucosides; C029366:hydroxykynurenine glucoside; D007737:Kynurenine