Generation of superoxide radicals by copper–glutathione complexes: Redox-consequences associated with their interaction with reduced glutathione

Probing the coordination properties of glutathione with transition metal ions (Cr2+,Mn2+,Fe2+,Co2+, Ni2+,Cu2+,Zn2+,Cd2+,Hg2+) by density functional theory

“…The electron transfer is mainly into 4s and 3d and only a little into the 4p orbital of metal ions (Cr 2+ , Mn 2+ , Fe 2+ , Co 2+ , Ni 2+ , Cu 2+ ) and the electrons from the 10 ), which reveals that Cu 2+ in these complexes has been reduced to Cu + during the coordination with GSH. Moreover, the reduction tendencies also occur with other metal cations in some complexes, especially in the monodentate complexes (GSH-M-1 and GSH-M-2), in which the amounts of charge transfer from GSH to metal cations are more than that of other complexes.…”

“…The results show that the charge transfer takes place in all complexes during the complexation reaction, which implies the presence of an interaction with a covalent contribution. 10 for Zn 2+ and Cd 2+ , respectively), Cu 2+ has the greatest tendency to be a fully occupied 3d 10 orbital. Due to a large effective nuclear charge, the charge transfer between Hg 2+ and GSH is more than that of Zn 2+ and Cd 2+ .…”

“…It has been suggested that GSH may serve as a primary defense against metal cation toxicity [4,5]. Reduced glutathione (GSH), present in nuclei at concentrations ranging from 1 and 10 mM, has been implied as a protective agent against heavy metal cation toxicity through forming complexes [6][7][8][9][10][11].…”

Menkes disease

“…3 In the cytoplasma copper is bound to small proteins such as metallothionein 4 and glutathione, 5 or copper-specific chaperones, and thereby the cell is protected from the toxic effects of the free ion. The three known copper-chaperons, CCS, ATOX1, and COX17, bind the copper ion and guide it to different cellular locations, securing efficient delivery of the metal to the enzymes.…”

Structural and Activity Changes in Renal Betaine Aldehyde Dehydrogenase Caused by Oxidants

“…Copper generates ROS (hydroxyl • OH and superoxide anion radical O 2 •-) by two mechanisms: Fenton and/or HaberWeiss chemistry (Jomova & Valko, 2011;Prousek, 2007) and by decreasing glutathione levels (Speisky et al, 2009). Glutathione has several functions including acting as a powerful cell antioxidant and as a copper chelating agent; therefore decreased glutathione levels can enhance oxidative stress (Mattie & Freedman, 2004;Steinebach & Wolterbeek, 1994).…”