title: Nitric oxide is reduced to HNO by proton-coupled nucleophilic attack by ascorbate, tyrosine, and other alcohols. A new route to HNO in biological media?
abstract: The role of NO in biology is well established. However, an increasing body of evidence suggests that azanone (HNO), could also be involved in biological processes, some of which are attributed to NO. In this context, one of the most important and yet unanswered questions is whether and how HNO is produced in vivo. A possible route concerns the chemical or enzymatic reduction of NO. In the present work, we have taken advantage of a selective HNO sensing method, to show that NO is reduced to HNO by biologically relevant alcohols with moderate reducing capacity, such as ascorbate or tyrosine. The proposed mechanism involves a nucleophilic attack to NO by the alcohol, coupled to a proton transfer (PCNA: proton-coupled nucleophilic attack) and a subsequent decomposition of the so-produced radical to yield HNO and an alkoxyl radical.
authors.affiliation: †Departamento de Química Inorgánica, Analítica y Química Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, INQUIMAE-CONICET, Ciudad Universitaria, (C1428EGA) Buenos Aires, Argentina.
authors.forename: Sebastián A
authors.initials: SA
authors.lastname: Suarez
authors.affiliation: †Departamento de Química Inorgánica, Analítica y Química Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, INQUIMAE-CONICET, Ciudad Universitaria, (C1428EGA) Buenos Aires, Argentina.|‡Departamento de Física, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Paraje El Pozo, Santa Fe 3000, Argentina.
authors.forename: Nicolás I
authors.initials: NI
authors.lastname: Neuman
authors.affiliation: †Departamento de Química Inorgánica, Analítica y Química Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, INQUIMAE-CONICET, Ciudad Universitaria, (C1428EGA) Buenos Aires, Argentina.
authors.forename: Martina
authors.initials: M
authors.lastname: Muñoz
authors.affiliation: †Departamento de Química Inorgánica, Analítica y Química Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, INQUIMAE-CONICET, Ciudad Universitaria, (C1428EGA) Buenos Aires, Argentina.
authors.forename: Lucía
authors.initials: L
authors.lastname: Álvarez
authors.affiliation: †Departamento de Química Inorgánica, Analítica y Química Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, INQUIMAE-CONICET, Ciudad Universitaria, (C1428EGA) Buenos Aires, Argentina.
authors.forename: Damián E
authors.initials: DE
authors.lastname: Bikiel
authors.affiliation: ‡Departamento de Física, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Paraje El Pozo, Santa Fe 3000, Argentina.
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Brondino
authors.affiliation: §Department of Chemistry and Pharmacy, Friedrich-Alexander University Erlangen-Nuremberg, Egerlandstrasse 1, 91058 Erlangen, Germany.
authors.forename: Ivana
authors.initials: I
authors.lastname: Ivanović-Burmazović
authors.affiliation: §Department of Chemistry and Pharmacy, Friedrich-Alexander University Erlangen-Nuremberg, Egerlandstrasse 1, 91058 Erlangen, Germany.
authors.forename: Jan Lj
authors.initials: JLj
authors.lastname: Miljkovic
authors.affiliation: §Department of Chemistry and Pharmacy, Friedrich-Alexander University Erlangen-Nuremberg, Egerlandstrasse 1, 91058 Erlangen, Germany.
authors.forename: Milos R
authors.initials: MR
authors.lastname: Filipovic
authors.affiliation: †Departamento de Química Inorgánica, Analítica y Química Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, INQUIMAE-CONICET, Ciudad Universitaria, (C1428EGA) Buenos Aires, Argentina.|⊥Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pab. II, (C1428EGA) Buenos Aires, Argentina.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Martí
authors.affiliation: †Departamento de Química Inorgánica, Analítica y Química Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, INQUIMAE-CONICET, Ciudad Universitaria, (C1428EGA) Buenos Aires, Argentina.
authors.forename: Fabio
authors.initials: F
authors.lastname: Doctorovich
mesh_terms: D000438:Alcohols / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D042783:Endothelial Cells / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism; D009589:Nitrogen Oxides / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D014443:Tyrosine / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000438:Alcohols; D009589:Nitrogen Oxides; C059688:alkoxyl radical; D009569:Nitric Oxide; D014443:Tyrosine; C039900:nitroxyl; D001205:Ascorbic Acid