The effect of oxygen, antioxidants, and superoxide radical on tyrosine phenoxyl radical dimerization

Hunter, Edward P. L.; Desrosiers, Marc F.; Simic, Michael G.

doi:10.1016/0891-5849(89)90064-6

Cited by 153 publications

(75 citation statements)

References 26 publications

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“…4 A). This may be due to either an increase in H202 yield or accelerated disappearance of 0°-, which is known to repair tyrosyl radical (24).…”

Section: Resultsmentioning

confidence: 99%

“…It also remains to be determined if other amino acids are oxidized by myeloperoxidase. Because L-tyrosine is the most easily oxidized aromatic amino acid (26), and phenols are known to be unusually susceptible to one electron transfer reactions (8)(9)(10), L-tyro- (24), L-tyrosine (9-11), vitamin E (24), and ascorbate (24). The repair reaction may explain both the stimulation of neutrophil-dependent dityrosine cross-linking by superoxide dismutase and the inhibition of myeloperoxidase-catalyzed BSA cross-linking by high concentrations of L-tyrosine.…”

Section: Discussionmentioning

confidence: 99%

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Tyrosyl radical generated by myeloperoxidase catalyzes the oxidative cross-linking of proteins.

Heinecke¹,

Li²,

Francis³

et al. 1993

J. Clin. Invest.

331

242

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Phagocytes generate H202 for use by a secreted heme enzyme, myeloperoxidase, to kill invading bacteria, viruses, and fungi. We have explored the possibility that myeloperoxidase might also convert L-tyrosine to a radical catalyst that cross-links proteins. Protein-bound tyrosyl residues exposed to myeloperoxidase, H202, and L-tyrosine were oxidized to oo'-dityrosine, a stable product of the tyrosyl radical. The cross-linking reaction required L-tyrosine but was independent of halide and free transition metal ions; the heme poisons azide and aminotriazole were inhibitory. Activated neutrophils likewise converted polypeptide tyrosines to dityrosine. The pathway for oxidation of peptide tyrosyl residues was dependent upon L-tyrosine and was inhibited by heme poisons and catalase. Dityrosine synthesis was little affected by plasma concentrations of Cl-and amino acids, suggesting that the reaction pathway might be physiologically relevant. The requirement for free L-tyrosine and H202 for dityrosine formation and the inhibition by heme poisons support the hypothesis that myeloperoxidase catalyzes the cross-linking of proteins by a peroxidative mechanism involving tyrosyl radical. In striking contrast to the pathways generally used to study protein oxidation in vitro, the reaction does not require free metal ions. We speculate that protein dityrosine cross-linking by myeloperoxidase may play a role in bacterial killing or injuring normal tissue. The intense fluorescence and stability of biphenolic compounds may allow dityrosine to act as a marker for proteins oxidatively damaged by myeloperoxidase in phagocyte-rich inflammatory lesions. (J.Clin. Invest. 1993Invest. . 91:2866Invest. -2872

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“…4 A). This may be due to either an increase in H202 yield or accelerated disappearance of 0°-, which is known to repair tyrosyl radical (24).…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tyrosyl radical generated by myeloperoxidase catalyzes the oxidative cross-linking of proteins.

Heinecke¹,

Li²,

Francis³

et al. 1993

J. Clin. Invest.

331

242

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“…O 2 . scavenges tyrosyl radical by acting as an electron donor (46,47). This reaction is blocked by superoxide dismutase, which catalyzes the dismutation of O 2 .…”

Section: Neutrophils Employ the Myeloperoxidase-h 2 O 2 System To Conmentioning

confidence: 99%

“…This reaction is blocked by superoxide dismutase, which catalyzes the dismutation of O 2 . to H 2 O 2 (46,47).…”

Section: Neutrophils Employ the Myeloperoxidase-h 2 O 2 System To Conmentioning

confidence: 99%

Human Phagocytes Employ the Myeloperoxidase-Hydrogen Peroxide System to Synthesize Dityrosine, Trityrosine, Pulcherosine, and Isodityrosine by a Tyrosyl Radical-dependent Pathway

Jacob

Cistola

Hsu

et al. 1996

Journal of Biological Chemistry

142

117

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Myeloperoxidase, a heme protein secreted by activated phagocytes, may be a catalyst for lipoprotein oxidation in vivo. Active myeloperoxidase is a component of human atherosclerotic lesions, and atherosclerotic tissue exhibits selective enrichment of protein dityrosine cross-links, a well characterized product of myeloperoxidase. Tyrosylation of lipoproteins with peroxidasegenerated tyrosyl radical generates multiple proteinbound tyrosine oxidation products in addition to dityrosine. The structural characterization of these products would thus serve as an important step in determining the role of myeloperoxidase in lipoprotein oxidation in the artery wall. We now report the identification and characterization of four distinct tyrosyl radical addition products generated by human phagocytes. Activated neutrophils synthesized three major fluorescent products from L-tyrosine; on reverse phase HPLC, each compound coeluted with fluorescent oxidation products formed by myeloperoxidase. We purified the oxidation products to apparent homogeneity by cation and anion exchange chromatographies and identified the compounds as dityrosine (3,3-dityrosine), trityrosine (3,3,5,3؆-trityrosine) and pulcherosine (5-[4؆-(2-carboxy-2-aminoethyl)phenoxy]3,3-dityrosine) by high resolution NMR spectroscopy and mass spectrometry. Additionally, we have found that dityrosine is a precursor to trityrosine, but not pulcherosine. In a search for a precursor to pulcherosine, we identified isodityrosine (3-[4-(2-carboxy-2-aminoethyl)phenoxy]tyrosine), a nonfluorescent product of L-tyrosine oxidation by human phagocytes. Our results represent the first identification of this family of tyrosyl radical addition products in a mammalian system. Moreover, these compounds may serve as markers specific for tyrosyl radical-mediated oxidative damage in atherosclerosis and other inflammatory conditions.

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“…2 and 3). For example, while XA was at least as efficient as 3HKyn and 3HAA in preventing AAPH-induced formation of PtdCho (36) and tyrosine (37).…”

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confidence: 99%

Antioxidant activities of some tryptophan metabolites: possible implication for inflammatory diseases.

Christen

Peterhans

Stocker

1990

Proc. Natl. Acad. Sci. U.S.A.

283

179

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The antioxidant properties of tryptophan and some of its oxidative metabolites were examined by measuring how efficiently they inhibited peroxyl radical-mediated oxidation of phosphatidyicholine liposomes and B-phycoerythrin.Low micromolar concentrations of 5-hydroxytryptophan, 3-hydroxykynurenine, xanthurenic acid, or 3-hydroxyanthranilic acid, but not their corresponding nonhydroxylated metabolic precursors, scavenged peroxyl radicals with high efficiency. In particular, 3-hydroxykynurenine and 3-hydroxyanthranilic acid protected B-phycoerythrin from peroxyl radical-mediated oxidative damage more effectively than equimolar amounts of either ascorbate or Trolox (a water-soluble analog of vitamin E). Enzyme activities involved or related to oxidative tryptophan metabolism, as well as endogenous concentrations of tryptophan and its metabolites, were determined within tissues of mice suffering from acute viral pneumonia.

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The effect of oxygen, antioxidants, and superoxide radical on tyrosine phenoxyl radical dimerization

Cited by 153 publications

References 26 publications

Tyrosyl radical generated by myeloperoxidase catalyzes the oxidative cross-linking of proteins.

Tyrosyl radical generated by myeloperoxidase catalyzes the oxidative cross-linking of proteins.

Human Phagocytes Employ the Myeloperoxidase-Hydrogen Peroxide System to Synthesize Dityrosine, Trityrosine, Pulcherosine, and Isodityrosine by a Tyrosyl Radical-dependent Pathway

Antioxidant activities of some tryptophan metabolites: possible implication for inflammatory diseases.

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