Dynamics of Dinitrosyl Iron Complex (DNIC) Formation with Low Molecular Weight Thiols

Autor(es)

Truzzi, Daniela R. ^{[1, 2, 3]} ; Augusto, Ohara ^[2] ; Iretskii, Alexei V. ^[4] ; Ford, Peter C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 - USA

^[2] Univ Sao Paulo, Inst Quim Sao Paulo, Dept Bioquim, Caixa Postal 26077, BR-05513970 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Dept Bioquim, Inst Quim Sao Paulo, Caixa Postal 26077, BR-05513970 Sao Paulo, SP - Brazil

^[4] Lake Super State Univ, Dept Chem & Environm Sci, Sault Sainte Marie, MI 49783 - USA

• Tipo de documento: Artigo Científico
• Fonte: Inorganic Chemistry; v. 58, n. 19, p. 13446-13456, OCT 7 2019.
• Citações Web of Science: 0

Resumo

Dinitrosyl iron complexes (DNICs) are ubiquitous in mammalian cells and tissues producing nitric oxide (NO) and have been argued to play key physiological and pathological roles. Nonetheless, the mechanism and dynamics of DNIC formation in aqueous media remain only partially understood. Here, we report a stopped-flow kinetics and density functional theory (DFT) investigation of the reaction of NO with ferrous ions and the low molecular weight thiols glutathione (GSH) and cysteine (CysSH) as well as the peptides WCGPC and WCGPY to produce DNICs in pH 7.4 aqueous media. With each thiol, a two-stage reaction pattern is observed. The first stage involves several rapidly established preequilibria leading to a ferrous intermediate concluded to have the composition F-II(NO)(RS)(2)(H2O)(x)(C). In the second stage, C undergoes rate-limiting, unimolecular autoreduction to give thiyl radical (RS center dot) plus the mononitrosyl Fe(I) complex Fe-I(NO)(RS)(H2O)v following the reactivity order of CysSH > W CGPC > W CGPY > GSH. Time course simulations using the experimentally determined kinetics parameters demonstrate that, at a NO flux characteristic of inflammation, DNICs will be rapidly formed from intracellular levels of ferrous iron and thiols. Furthermore, the proposed mechanism offers a novel pathway for S-nitroso thiol (RSNO) formation in a biological environment. (AU)

• Processo FAPESP: 17/02728-2 - Dinitrosilos complexos de ferro biomiméticos: formação e capacidade de S-nitrosação
• Beneficiário: Daniela Ramos Truzzi
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 14/09518-5 - Mecanismos de S-nitrosação de proteínas: cinética, mecanismo e implicações biológicas
• Beneficiário: Daniela Ramos Truzzi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado