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

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101731726 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-8006 (Electronic) Linking ISSN: 03044165 NLM ISO Abbreviation: Biochim Biophys Acta Gen Subj Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam : Elsevier
    • Subject Terms:
      Environmental Pollutants*/pharmacokinetics ; Environmental Pollutants*/toxicity ; Methylmercury Compounds*/pharmacokinetics ; Methylmercury Compounds*/toxicity; Brain/*metabolism ; Neurons/*metabolism; Animals ; Brain/pathology ; Cysteine/metabolism ; Humans ; Nerve Tissue Proteins/metabolism ; Neurons/pathology ; Selenoproteins/metabolism
    • Abstract:
      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 (R 1 S(e)-HgMe + R 2 -S(e)H ↔ R 1 S(e)H + R 2 -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.
      (Copyright © 2019 Elsevier B.V. All rights reserved.)
    • Grant Information:
      R01 ES020852 United States ES NIEHS NIH HHS
    • Contributed Indexing:
      Keywords: Exchange reaction; Methylation/demethylation; Neurotoxicity; Organomercurials; Rabenstein's Reaction; Thiol/selenol groups
    • Accession Number:
      0 (Environmental Pollutants)
      0 (Methylmercury Compounds)
      0 (Nerve Tissue Proteins)
      0 (Selenoproteins)
      K848JZ4886 (Cysteine)
    • Publication Date:
      Date Created: 20190120 Date Completed: 20200512 Latest Revision: 20200518
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.bbagen.2019.01.006
    • Accession Number:
      30659885