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

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 toxicolog...

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Published inBiochimica 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
LanguageEnglish
Published Netherlands Elsevier B.V 01.12.2019
Subjects
Online AccessGet full text
ISSN0304-4165
1872-8006
1872-8006
DOI10.1016/j.bbagen.2019.01.006

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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 (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.
AbstractList 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.
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 S(e)-HgMe + R -S(e)H ↔ R S(e)H + R -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.
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.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.
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.
ArticleNumber 129284
Author Farina, Marcelo
Oliveira, Cláudia S.
Nogara, Pablo A.
Schmitz, Gabriela L.
Rocha, João B.T.
Aschner, Michael
Piquini, Paulo C.
Author_xml – sequence: 1
  givenname: Pablo A.
  surname: Nogara
  fullname: Nogara, Pablo A.
  organization: Departamento de Bioquímica e Biologia Molecular, CCNE, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
– sequence: 2
  givenname: Cláudia S.
  surname: Oliveira
  fullname: Oliveira, Cláudia S.
  organization: Departamento de Bioquímica e Biologia Molecular, CCNE, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
– sequence: 3
  givenname: Gabriela L.
  surname: Schmitz
  fullname: Schmitz, Gabriela L.
  organization: Departamento de Bioquímica e Biologia Molecular, CCNE, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
– sequence: 4
  givenname: Paulo C.
  surname: Piquini
  fullname: Piquini, Paulo C.
  organization: Departamento de Física, CCNE, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil
– sequence: 5
  givenname: Marcelo
  surname: Farina
  fullname: Farina, Marcelo
  organization: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
– sequence: 6
  givenname: Michael
  surname: Aschner
  fullname: Aschner, Michael
  organization: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA
– sequence: 7
  givenname: João B.T.
  surname: Rocha
  fullname: Rocha, João B.T.
  email: jbtrocha@gmail.com
  organization: Departamento de Bioquímica e Biologia Molecular, CCNE, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30659885$$D View this record in MEDLINE/PubMed
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Issue 12
Keywords Organomercurials
Neurotoxicity
Methylation/demethylation
Exchange reaction
Rabenstein's Reaction
Thiol/selenol groups
Language English
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Snippet 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...
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SubjectTerms 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
Title Methylmercury's chemistry: From the environment to the mammalian brain
URI https://dx.doi.org/10.1016/j.bbagen.2019.01.006
https://www.ncbi.nlm.nih.gov/pubmed/30659885
https://www.proquest.com/docview/2179401643
https://www.proquest.com/docview/2221023424
Volume 1863
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