Abstract
Toxic mercury (Hg) exposures inhibit selenium (Se)-dependent enzymes (selenoenzymes) required in the brain. Selenocysteine (Sec), the 21st genetically encoded amino acid, is the most powerful intracellular nucleophile, making it vulnerable to electrophiles such as Hg. The human genome includes 25 genes which express selenoenzymes with essential functions that control cellular redox status, thyroid hormone and calcium-dependent processes, immune responses, and other vital processes. Methyl-Hg (CH3Hg) binds to cysteine (Cys) to form the CH3Hg-Cys adducts which predominate in tissues. Due to molecular similarities between methionine (Met) and CH3Hg-Cys, cellular membrane transporters actively mobilize this species across membranes and into proteins. Because many selenoenzymes directly act upon or work in concert with thiomolecules, the CH3Hg-Cys in these molecules function as a suicide substrate that brings Hg into direct contact with the selenoenzyme’s active site Sec. Since Hg’s affinity for Se is far higher than its affinity for sulfur, CH3Hg exchanges partners to form CH3Hg-Sec, irreversibly inhibiting the enzyme and subsequently forming insoluble HgSe. Exposures to CH3Hg can impair Se availability in maternal, placental, and fetal tissues, but provided tissue reservoirs and intakes of Se are sufficient to ensure Sec synthesis proceeds without hindrance, the oxidative damage and other pathological consequences of high exposures are averted. Exposure to toxic amounts of Hg overcome the ability of these sources to offset Se losses. Mercury toxicity’s biochemical mechanisms, Se-dependent protective effects, variability in dose effects, prolonged latency, tissue specificity, and enhanced fetal vulnerability to high exposures are becoming increasingly well understood.
Abbreviations
- AP-1:
-
Activator protein 1
- ApoER2:
-
Apolipoprotein E receptor 2
- CH3Hg:
-
Methylmercury
- CH3HgCH3:
-
Dimethylmercury
- Cys:
-
Cysteine
- DIO:
-
Deiodinase
- DIO1:
-
Iodothyronine deiodinase 1
- GPx:
-
Glutathione peroxidase
- GSH:
-
Glutathione
- GSSH:
-
Glutathione (oxidized form)
- H2O2:
-
Hydrogen peroxide
- Hg+:
-
Oxidized mercury
- Hg+, Hg2+:
-
Inorganic mercury
- Hg0:
-
Elemental mercury
- HSe−:
-
Selenide
- LAT1:
-
Large neutral amino acid transporter
- Met:
-
Methionine
- MsrB:
-
Methionine sulfoxide reductase B
- NF-κB:
-
Nuclear factor kappa light-chain enhancer of activated B cells
- OOH:
-
Hydroperoxo species
- Prx:
-
Peroxyredoxins
- RNR:
-
Ribonucleotide reductase
- ROO.:
-
Peroxyl radical
- RSe−:
-
Selenoate
- RSH:
-
Sulfhydryl
- Sec:
-
Selenocysteine
- SeMet:
-
Selenomethionine
- SeO3:
-
Selenium trioxide
- SeO32−:
-
Selenite
- SeO42−:
-
Selenate
- Ser:
-
Serine
- TGR:
-
Thioredoxin-glutathione reductase
- Trx-(SH)2:
-
Thioredoxin
- TRx1:
-
Thioredoxin reductase 1
- TRx2:
-
Thioredoxin reductase 2
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Ralston, N.V.C. (2021). Mercury’s Neurotoxic Effects on Brain Selenoenzymes. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-030-71519-9_236-1
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DOI: https://doi.org/10.1007/978-3-030-71519-9_236-1
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