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dc.contributor.authorGurer-Orhan, H
dc.contributor.authorErcal, N
dc.contributor.authorMare, S
dc.contributor.authorPennathur, S
dc.contributor.authorOrhan, H
dc.contributor.authorHeinecke, JW
dc.date.accessioned2019-12-16T10:29:25Z
dc.date.available2019-12-16T10:29:25Z
dc.date.issued2006
dc.identifier.issn0264-6021
dc.identifier.urihttps://doi.org/10.1042/BJ20051964
dc.identifier.urihttp://hdl.handle.net/11655/20121
dc.description.abstractIn vitro studies demonstrate that the hydroxyl radical converts L-phenylalanine into in-tyrosine, an unnatural isomer of L-tyrosine. Quantification of m-tyrosine has been widely used as an index of oxidative damage in tissue proteins. However, the possibility that m-tyrosine might be generated oxidatively from free L-phenylalanine that could subsequently be incorporated into proteins as an L-tyrosine analogue has received little attention. In the present study, we demonstrate that free m-tyrosine is toxic to cultured CHO (Chinese-hamster ovary) cells. We readily detected radiolabelled material in proteins isolated from CHO cells that had been incubated with m-[C-14]tyrosine, suggesting that the oxygenated amino acid was taken up and incorporated into cellular proteins. in-Tyrosine was detected by co-elution with authentic material on HPLC and by tandem mass spectrometric analysis in acid hydrolysates of proteins isolated from CHO cells exposed to m-tyrosine, indicating that free m-tyrosine was incorporated intact rather than being metabolized to other products that were subsequently incorporated into proteins. Incorporation of m-tyrosine into cellular proteins was sensitive to inhibition by cycloheximide, suggesting that protein synthesis was involved. Protein synthesis using a cell-free transcription/translation system showed that m-tyrosine was incorporated into proteins in vitro by a mechanism that may involve L-phenylalanine-tRNA synthetase. Collectively, these observations indicate that m-tyrosine is toxic to cells by a pathway that may involve incorporation of the oxidized amino acid into proteins. Thus misincorporation of free oxidized amino acids during protein synthesis may represent an alternative mechanism for oxidative stress and tissue injury during aging and disease.
dc.language.isoen
dc.publisherPortland Press Ltd
dc.relation.isversionof10.1042/BJ20051964
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectBiochemistry & Molecular Biology
dc.titleMisincorporation Of Free M-Tyrosine Cytotoxic Mechanism For Oxidized A Into Cellular Proteins: A Potential Amino Acids
dc.typeinfo:eu-repo/semantics/article
dc.relation.journalBiochemical Journal
dc.contributor.departmentEczacılık Temel Bilimleri
dc.identifier.volume395
dc.identifier.startpage277
dc.identifier.endpage284
dc.description.indexWoS


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