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Reaction of Hydrogen Sulfide with Disulfide and Sulfenic Acid to Form the Strongly Nucleophilic Persulfide.
J Biol Chem. 2015 Nov 06; 290(45):26866-26880.JB

Abstract

Hydrogen sulfide (H2S) is increasingly recognized to modulate physiological processes in mammals through mechanisms that are currently under scrutiny. H2S is not able to react with reduced thiols (RSH). However, H2S, more precisely HS(-), is able to react with oxidized thiol derivatives. We performed a systematic study of the reactivity of HS(-) toward symmetric low molecular weight disulfides (RSSR) and mixed albumin (HSA) disulfides. Correlations with thiol acidity and computational modeling showed that the reaction occurs through a concerted mechanism. Comparison with analogous reactions of thiolates indicated that the intrinsic reactivity of HS(-) is 1 order of magnitude lower than that of thiolates. In addition, H2S is able to react with sulfenic acids (RSOH). The rate constant of the reaction of H2S with the sulfenic acid formed in HSA was determined. Both reactions of H2S with disulfides and sulfenic acids yield persulfides (RSSH), recently identified post-translational modifications. The formation of this derivative in HSA was determined, and the rate constants of its reactions with a reporter disulfide and with peroxynitrite revealed that persulfides are better nucleophiles than thiols, which is consistent with the α effect. Experiments with cells in culture showed that treatment with hydrogen peroxide enhanced the formation of persulfides. Biological implications are discussed. Our results give light on the mechanisms of persulfide formation and provide quantitative evidence for the high nucleophilicity of these novel derivatives, setting the stage for understanding the contribution of the reactions of H2S with oxidized thiol derivatives to H2S effector processes.

Authors+Show Affiliations

Laboratorios de Enzimología, Universidad de la República, 11400 Montevideo, Uruguay; Center for Free Radical and Biomedical Research, Universidad de la República, 11400 Montevideo, Uruguay.Department of Chemistry and Pharmacy, Division of Bioinorganic Chemistry, Friedrich-Alexander University of Erlangen-Nuremberg, 91058 Erlangen, Germany.Química Teórica y Computacional, Universidad de la República, 11400 Montevideo, Uruguay.Química Teórica y Computacional, Universidad de la República, 11400 Montevideo, Uruguay.Center for Free Radical and Biomedical Research, Universidad de la República, 11400 Montevideo, Uruguay; Fisicoquímica Biológica, Facultad de Ciencias, Universidad de la República, 11400 Montevideo, Uruguay.Department of Chemistry and Pharmacy, Division of Bioinorganic Chemistry, Friedrich-Alexander University of Erlangen-Nuremberg, 91058 Erlangen, Germany. Electronic address: milos.filipovic@fau.de.Laboratorios de Enzimología, Universidad de la República, 11400 Montevideo, Uruguay; Center for Free Radical and Biomedical Research, Universidad de la República, 11400 Montevideo, Uruguay. Electronic address: beatriz.alvarez@fcien.edu.uy.

Pub Type(s)

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

Language

eng

PubMed ID

26269587

Citation

Cuevasanta, Ernesto, et al. "Reaction of Hydrogen Sulfide With Disulfide and Sulfenic Acid to Form the Strongly Nucleophilic Persulfide." The Journal of Biological Chemistry, vol. 290, no. 45, 2015, pp. 26866-26880.
Cuevasanta E, Lange M, Bonanata J, et al. Reaction of Hydrogen Sulfide with Disulfide and Sulfenic Acid to Form the Strongly Nucleophilic Persulfide. J Biol Chem. 2015;290(45):26866-26880.
Cuevasanta, E., Lange, M., Bonanata, J., Coitiño, E. L., Ferrer-Sueta, G., Filipovic, M. R., & Alvarez, B. (2015). Reaction of Hydrogen Sulfide with Disulfide and Sulfenic Acid to Form the Strongly Nucleophilic Persulfide. The Journal of Biological Chemistry, 290(45), 26866-26880. https://doi.org/10.1074/jbc.M115.672816
Cuevasanta E, et al. Reaction of Hydrogen Sulfide With Disulfide and Sulfenic Acid to Form the Strongly Nucleophilic Persulfide. J Biol Chem. 2015 Nov 6;290(45):26866-26880. PubMed PMID: 26269587.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reaction of Hydrogen Sulfide with Disulfide and Sulfenic Acid to Form the Strongly Nucleophilic Persulfide. AU - Cuevasanta,Ernesto, AU - Lange,Mike, AU - Bonanata,Jenner, AU - Coitiño,E Laura, AU - Ferrer-Sueta,Gerardo, AU - Filipovic,Milos R, AU - Alvarez,Beatriz, Y1 - 2015/08/12/ PY - 2015/06/16/received PY - 2015/8/14/entrez PY - 2015/8/14/pubmed PY - 2016/5/7/medline KW - disulfide KW - hydrodisulfide KW - hydrogen sulfide KW - kinetics KW - persulfide KW - sulfenic acid KW - sulfhydryl KW - thiol SP - 26866 EP - 26880 JF - The Journal of biological chemistry JO - J Biol Chem VL - 290 IS - 45 N2 - Hydrogen sulfide (H2S) is increasingly recognized to modulate physiological processes in mammals through mechanisms that are currently under scrutiny. H2S is not able to react with reduced thiols (RSH). However, H2S, more precisely HS(-), is able to react with oxidized thiol derivatives. We performed a systematic study of the reactivity of HS(-) toward symmetric low molecular weight disulfides (RSSR) and mixed albumin (HSA) disulfides. Correlations with thiol acidity and computational modeling showed that the reaction occurs through a concerted mechanism. Comparison with analogous reactions of thiolates indicated that the intrinsic reactivity of HS(-) is 1 order of magnitude lower than that of thiolates. In addition, H2S is able to react with sulfenic acids (RSOH). The rate constant of the reaction of H2S with the sulfenic acid formed in HSA was determined. Both reactions of H2S with disulfides and sulfenic acids yield persulfides (RSSH), recently identified post-translational modifications. The formation of this derivative in HSA was determined, and the rate constants of its reactions with a reporter disulfide and with peroxynitrite revealed that persulfides are better nucleophiles than thiols, which is consistent with the α effect. Experiments with cells in culture showed that treatment with hydrogen peroxide enhanced the formation of persulfides. Biological implications are discussed. Our results give light on the mechanisms of persulfide formation and provide quantitative evidence for the high nucleophilicity of these novel derivatives, setting the stage for understanding the contribution of the reactions of H2S with oxidized thiol derivatives to H2S effector processes. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/26269587/Reaction_of_Hydrogen_Sulfide_with_Disulfide_and_Sulfenic_Acid_to_Form_the_Strongly_Nucleophilic_Persulfide_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)49456-6 DB - PRIME DP - Unbound Medicine ER -