title: Kinetics of 3-nitrotyrosine modification on exposure to hypochlorous acid.
abstract: The markers 3-nitrotyrosine and 3-chlorotyrosine are measured as surrogates for reactive nitrogen species and hypochlorous acid respectively, which are both elevated in inflamed human tissues. Previous studies reported a loss of 3-nitrotyrosine when exposed to hypochlorous acid, suggesting that observations of 3-nitrotyrosine underestimate the presence of reactive nitrogen species in diseased tissue (Whiteman and Halliwell, Biochemical and Biophysical Research Communications, 258, 168-172 (1999)). This report evaluates the significance of 3-nitrotyrosine loss by measuring the kinetics of the reaction between 3-nitrotyrosine and hypochlorous acid. The results demonstrate that 3-nitrotyrosine is chlorinated by hypochlorous acid or chloramines to form 3-chloro-5-nitrotyrosine. As 3-nitrotyrosine from in vivo samples is usually found within proteins rather than as free amino acid, we also examined the reaction of 3-nitrotyrosine modification in the context of peptides. The chlorination of 3-nitrotyrosine in peptides was observed to occur up to 700-fold faster than control reactions using equivalent amino acid mixtures. These results further advance our understanding of tyrosine chlorination and the use of 3-nitrotyrosine formed in vivo as a biomarker of reactive nitrogen species.
authors.affiliation: Department of Basic Sciences, School of Medicine, Loma Linda University , Loma Linda, CA , USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Curtis
authors.forename: J W
authors.initials: JW
authors.lastname: Neidigh
mesh_terms: D015415:Biomarkers / Q000032:analysis; D002700:Chloramines / Q000737:chemistry* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006997:Hypochlorous Acid / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002700:Chloramines; D010446:Peptide Fragments; D026361:Reactive Nitrogen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D006997:Hypochlorous Acid; D009195:Peroxidase
keywords: 3-chlorotyrosine; biomarker; chloramine; protein damage; reactive species