Methylmercury's chemistry: From the environment to the mammalian brain

Methylmercury displays pro-adipogenic properties in rainbow trout preadipocytes

“…More specifically, uptake of MeHg-chloride seems to occur via passive diffusion and uptake of MeHg-L-cysteine via a carrier protein (Heggland et al, 2009). In the present study, as the culture medium contained L-cysteine (1 mM) and as MeHg has a higher affinity for sulfhydryl groups than for chloride ions (reviewed by Nogara et al (2019)), MeHg was most likely transported via membrane transport protein under the form of MeHg-L-cysteine complex. A plausible transporter candidate is the system L-type large neutral amino acid transporter (LAT) (Heggland et al, 2009).…”

Chalcogen–mercury bond formation and disruption in model Rabenstein's reactions: A computational analysis

“…Furthermore, the formation of R Se HgCH 3 complexes is more favorable than R S HgCH 3 , due to the higher binding affinity between CH 3 Hg + and SeH. 4,[7][8][9][10] The GPx and TrxR are important selenoenzymes involved in the cell antioxidant defense, cell proliferation, and redox-regulated signaling cascades. GPx is able to reduce hydrogen peroxide and/or organic hydroperoxides to water and/or the corresponding alcohols, respectively, 11,12 while the TrxR can reduce many substrates, such as the oxidized thioredoxin, peroxides, and other disulfide proteins (Scheme 1a,b).…”

“…13,14 It is supposed that the GPx and TrxR inhibition by CH 3 Hg + occurs via the binding of CH 3 Hg + to the selenium atom of Sec in their active site, leading to the interruption of the catalytic cycle (Scheme 1c,d), and consequently increasing the reactive oxygen species levels, causing cell death. 4,15 However, CH 3 Hg + mechanism of action is still not well understood and computational methods have been applied to gain insight into methylmercury chemistry with cysteine and selenocysteine. Particularly, Schreckenbach and coworkers carried out an extensive analysis on structural, electronic, and thermodynamic properties of methylmercury complexes with cysteine and selenocysteine, but also on the chalcogenophilicity of mercury, assessing that Hg S bond has a higher bond dissociation energy than Hg Se and Hg Te in different compounds ranging from small molecules to large complexes.…”

“…1,2 Several studies have demonstrated that the CH 3 Hg + toxicity might involve its interaction with thioprotein and selenoprotein (due to the high affinity of mercury to sulfur and selenium atoms present in cysteine [Cys] and selenocysteine [Sec] residues, respectively), disrupting their normal function. 3,4 CH 3 Hg + might bind to the Cys residue in many proteins and peptides, such as thioredoxin (Trx) and glutathione (GSH), which are the thioredoxin reductase (TrxR) and glutathione peroxidase (GPx) substrates, leading to the decrease in the active concentration of these important substrates. In addition, the adducts between Trx and GSH with CH 3 Hg + (Trx HgCH 3 and GS HgCH 3 ) might deliver the CH 3 Hg + moiety to its respective enzymes, inhibiting them.…”

Integrating Diphenyl Diselenide and Its Mehg+ Detoxificant Mechanism on a Conceptual DFT Framework

“…The toxicity of the soft electrophilic MeHg + is mediated by inactivation of proteins containing soft nucleophilic sites (e.g., thiol-and selenol-containing proteins) [3][4][5][6][7]. MeHg + has an extremely high affinity for -SH and -SeH groups [5,8]. Experimental and theoretical studies have indicated that the affinity of MeHg + for -SeH is greater than for -SH groups [5].…”