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

• Published in: Biochimica et biophysica acta. General subjects Vol. 1863; no. 12; p. 129284
• Main Authors: Nogara, Pablo A., Oliveira, Cláudia S., Schmitz, Gabriela L., Piquini, Paulo C., Farina, Marcelo, Aschner, Michael, Rocha, João B.T.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2019
• Subjects: absorption; acetyl coenzyme A; albumins; Animalia; Animals; brain; Brain - metabolism; Brain - pathology; cysteine; Cysteine - metabolism; Environmental Pollutants - pharmacokinetics; Environmental Pollutants - toxicity; Exchange reaction; excretion; fish; hemoglobin; homocysteine; Humans; Methylation/demethylation; methylmercury compounds; Methylmercury Compounds - pharmacokinetics; Methylmercury Compounds - toxicity; molecular weight; Nerve Tissue Proteins - metabolism; Neurons - metabolism; Neurons - pathology; Neurotoxicity; neurotoxins; Organomercurials; Rabenstein's Reaction; rice; selenoproteins; Selenoproteins - metabolism; Thiol/selenol groups; thiols; Organomercurials; Neurotoxicity; Methylation/demethylation; Exchange reaction; Rabenstein's Reaction; Thiol/selenol groups
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2019.01.006

Methylmercury is a neurotoxicant that is found in fish and rice. MeHg's toxicity is mediated by blockage of -SH and -SeH groups of proteins. However, the identification of MeHg's targets is elusive. Here we focus on the chemistry of MeHg in the abiotic and biotic environment. The toxicological chemistry of MeHg is complex in metazoans, but at the atomic level it can be explained by exchange reactions of MeHg bound to –S(e)H with another free –S(e)H group (R1S(e)-HgMe + R2-S(e)H ↔ R1S(e)H + R2-S(e)-HgMe). This reaction was first studied by professor Rabenstein and here it is referred as the “Rabenstein's Reaction”. The absorption, distribution, and excretion of MeHg in the environment and in the body of animals will be dictated by Rabenstein's reactions. The affinity of MeHg by thiol and selenol groups and the exchange of MeHg by Rabenstein's Reaction (which is a diffusion controlled reaction) dictates MeHg's neurotoxicity. However, it is important to emphasize that the MeHg exchange reaction velocity with different types of thiol- and selenol-containing proteins will also depend on protein-specific structural and thermodynamical factors. New experimental approaches and detailed studies about the Rabenstein's reaction between MeHg with low molecular mass thiol (LMM-SH) molecules (cysteine, GSH, acetyl-CoA, lipoate, homocysteine) with abundant high molecular mass thiol (HMM-SH) molecules (albumin, hemoglobin) and HMM-SeH (GPxs, Selenoprotein P, TrxR1-3) are needed. The study of MeHg migration from –S(e)-Hg- bonds to free –S(e)H groups (Rabenstein's Reaction) in pure chemical systems and neural cells (with special emphasis to the LMM-SH and HMM-S(e)H molecules cited above) will be critical to developing realistic constants to be used in silico models that will predict the distribution of MeHg in humans. •MeHg's toxicity is mediated by interactions with -SH and -SeH groups from proteins.•In biological fluids, MeHg is found forming R-S(e)-Hg-CH3 complexes.•The R-S(e)-Hg-CH3 complexes can exchange with free -SH and -SeH (Rabenstein's reactions).•The absorption, distribution, and excretion of MeHg is dictated by the Rabenstein's reactions.•MeHg exchange reaction velocity depends on protein-specific structural and thermodynamical factors.