Novel protein modification by kynurenine in human lenses

Santiago Vazquez, J. Andrew Aquilina, Joanne F. Jamie, Margaret M. Sheil, Roger J W Truscott

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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-β-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.

LanguageEnglish
Pages4867-4873
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number7
DOIs
Publication statusPublished - 15 Feb 2002
Externally publishedYes

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Kynurenine
Lenses
Crystallins
Proteins
Tryptophan
Fluorescence
Deamination
Glucosides
Post Translational Protein Processing
Metabolites
Histidine
Lysine
Hydrolysis
Up-Regulation
Color
Tissue
Amino Acids
Acids

Cite this

Vazquez, S., Aquilina, J. A., Jamie, J. F., Sheil, M. M., & Truscott, R. J. W. (2002). Novel protein modification by kynurenine in human lenses. Journal of Biological Chemistry, 277(7), 4867-4873. https://doi.org/10.1074/jbc.M107529200
Vazquez, Santiago ; Aquilina, J. Andrew ; Jamie, Joanne F. ; Sheil, Margaret M. ; Truscott, Roger J W. / Novel protein modification by kynurenine in human lenses. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 7. pp. 4867-4873.
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Vazquez, S, Aquilina, JA, Jamie, JF, Sheil, MM & Truscott, RJW 2002, 'Novel protein modification by kynurenine in human lenses', Journal of Biological Chemistry, vol. 277, no. 7, pp. 4867-4873. https://doi.org/10.1074/jbc.M107529200

Novel protein modification by kynurenine in human lenses. / Vazquez, Santiago; Aquilina, J. Andrew; Jamie, Joanne F.; Sheil, Margaret M.; Truscott, Roger J W.

In: Journal of Biological Chemistry, Vol. 277, No. 7, 15.02.2002, p. 4867-4873.

Research output: Contribution to journalArticleResearchpeer-review

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