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Homolytic pathways drive peroxynitrite-dependent Trolox C oxidation.
Chem Res Toxicol. 2004 Oct; 17(10):1377-84.CR

Abstract

Peroxynitrite is a powerful oxidant implicated as a mediator in nitric oxide ((*)NO)- and superoxide (O(2)(*)(-))-dependent toxicity. Peroxynitrite homolyzes after (i) protonation, yielding hydroxyl ((*)OH) and nitrogen dioxide ((*)NO(2)) free radicals, and (ii) reaction with carbon dioxide (CO(2)), yielding carbonate radical anion (CO(3)(*)(-)) and (*)NO(2). Additionally, peroxynitrite reacts directly with several biomolecules. It is currently accepted that alpha-tocopherol is one important antioxidant in lipid compartments and its reactions with peroxynitrite or peroxynitrite-derived radicals may be relevant in vivo. Previous reports on the peroxynitrite reaction with Trolox C (TxOH)--an alpha-tocopherol water soluble analogue--suggested a direct and fast reaction. This was unexpected to us as judged from the known reactivities of peroxynitrite with other phenolic compounds; thus, we thoroughly investigated the kinetics and mechanism of the reaction of peroxynitrite with TxOH and its modulation by CO(2). Direct electron paramagnetic resonance studies revealed that Trolox C phenoxyl radical (TxO(*)) was the only paramagnetic species detected either in the absence or in the presence of CO(2). Stopped-flow spectrophotometry experiments revealed a sequential reaction mechanism, with the intermediacy of TxO(*) and the production of Trolox C quinone (TxQ). Reactions were zero-order with respect to TxOH and first-order in peroxynitrite and CO(2), demonstrating that the reaction of peroxynitrite with TxOH is indirect. In agreement, TxOH was unable to inhibit the direct peroxynitrite-mediated oxidation of methionine to methionine sulfoxide. TxOH oxidation yields to TxO(*) and TxQ with respect to peroxynitrite were approximately 60 and approximately 31%, respectively, and increased to approximately 73 and approximately 40%, respectively, in the presence of CO(2). At peroxynitrite excess over TxOH, the kinetics and mechanism of oxidation are more complex and involve the reactions of CO(3)(*)(-) with TxO(*) and the possible intermediacy of unstable NO(2)-TxOH adducts. Taken together, our results strongly support that H(+)- or CO(2)-catalyzed homolysis of peroxynitrite is required to cause TxOH, and hence, alpha-tocopherol oxidation.

Authors+Show Affiliations

Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15487899

Citation

Botti, Horacio, et al. "Homolytic Pathways Drive Peroxynitrite-dependent Trolox C Oxidation." Chemical Research in Toxicology, vol. 17, no. 10, 2004, pp. 1377-84.
Botti H, Trujillo M, Batthyány C, et al. Homolytic pathways drive peroxynitrite-dependent Trolox C oxidation. Chem Res Toxicol. 2004;17(10):1377-84.
Botti, H., Trujillo, M., Batthyány, C., Rubbo, H., Ferrer-Sueta, G., & Radi, R. (2004). Homolytic pathways drive peroxynitrite-dependent Trolox C oxidation. Chemical Research in Toxicology, 17(10), 1377-84.
Botti H, et al. Homolytic Pathways Drive Peroxynitrite-dependent Trolox C Oxidation. Chem Res Toxicol. 2004;17(10):1377-84. PubMed PMID: 15487899.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Homolytic pathways drive peroxynitrite-dependent Trolox C oxidation. AU - Botti,Horacio, AU - Trujillo,Madia, AU - Batthyány,Carlos, AU - Rubbo,Homero, AU - Ferrer-Sueta,Gerardo, AU - Radi,Rafael, PY - 2004/10/19/pubmed PY - 2005/3/30/medline PY - 2004/10/19/entrez SP - 1377 EP - 84 JF - Chemical research in toxicology JO - Chem Res Toxicol VL - 17 IS - 10 N2 - Peroxynitrite is a powerful oxidant implicated as a mediator in nitric oxide ((*)NO)- and superoxide (O(2)(*)(-))-dependent toxicity. Peroxynitrite homolyzes after (i) protonation, yielding hydroxyl ((*)OH) and nitrogen dioxide ((*)NO(2)) free radicals, and (ii) reaction with carbon dioxide (CO(2)), yielding carbonate radical anion (CO(3)(*)(-)) and (*)NO(2). Additionally, peroxynitrite reacts directly with several biomolecules. It is currently accepted that alpha-tocopherol is one important antioxidant in lipid compartments and its reactions with peroxynitrite or peroxynitrite-derived radicals may be relevant in vivo. Previous reports on the peroxynitrite reaction with Trolox C (TxOH)--an alpha-tocopherol water soluble analogue--suggested a direct and fast reaction. This was unexpected to us as judged from the known reactivities of peroxynitrite with other phenolic compounds; thus, we thoroughly investigated the kinetics and mechanism of the reaction of peroxynitrite with TxOH and its modulation by CO(2). Direct electron paramagnetic resonance studies revealed that Trolox C phenoxyl radical (TxO(*)) was the only paramagnetic species detected either in the absence or in the presence of CO(2). Stopped-flow spectrophotometry experiments revealed a sequential reaction mechanism, with the intermediacy of TxO(*) and the production of Trolox C quinone (TxQ). Reactions were zero-order with respect to TxOH and first-order in peroxynitrite and CO(2), demonstrating that the reaction of peroxynitrite with TxOH is indirect. In agreement, TxOH was unable to inhibit the direct peroxynitrite-mediated oxidation of methionine to methionine sulfoxide. TxOH oxidation yields to TxO(*) and TxQ with respect to peroxynitrite were approximately 60 and approximately 31%, respectively, and increased to approximately 73 and approximately 40%, respectively, in the presence of CO(2). At peroxynitrite excess over TxOH, the kinetics and mechanism of oxidation are more complex and involve the reactions of CO(3)(*)(-) with TxO(*) and the possible intermediacy of unstable NO(2)-TxOH adducts. Taken together, our results strongly support that H(+)- or CO(2)-catalyzed homolysis of peroxynitrite is required to cause TxOH, and hence, alpha-tocopherol oxidation. SN - 0893-228X UR - https://www.unboundmedicine.com/medline/citation/15487899/Homolytic_pathways_drive_peroxynitrite_dependent_Trolox_C_oxidation_ DB - PRIME DP - Unbound Medicine ER -