01 April 2005 : Original article
Toxicity induced by Hg2+ on choline acetyltransferase activity from E. electricus (L.) electrocytes: the protective effect of 2,3 dimercapto-propanol (BAL).Nilson Nunes-Tavares, Rafael Hospodar Felippe Valverde, Glauce Maria Nunes Araújo, Aida Hassón-Voloch
Med Sci Monit 2005; 11(4): BR100-105 :: ID: 15868
BACKGROUND: The effect of mercury (Hg(2+)) on the activity of choline acetyltransferase (ChAT) from electrocytes of Electrophorus electricus (L.) was studied due to the importance of this enzyme and acetylcholine in many neurochemical functions such as arousal, learning, and memory. MATERIAL/METHODS: Mercury, which has affinity to thiol groups, acted as a potent inhibitor of ChAT, which was obtained by differential centrifugation and ammonium sulfate precipitation, at 80%, from the main electric organ homogenate. RESULTS: Mercury inhibition presents different kinetic behaviors for both enzyme substrates: noncompetitive to choline and of mixed type to AcCoA, with inhibition constants on the order of 0.5 to 1.0 microM. The enzyme activity was recovered using 2,3 dimercapto-propanol (BAL), a well-known chelate for sulphydryl groups and metals, which acted as a protecting agent and was able to revert the Hg(2+) inhibition at a concentration of 10 (-6) M. After treatment with this metal and in the presence of 2,3 dimercapto-propanol, 70% of the enzyme activity was recovered for AcCoA and 80% for choline. CONCLUSIONS: The observed inhibition is likely due to direct protein interaction, because the addition of BAL reversed the effects of HgCl(2) on ChAT activity. The results cast new light on the mechanisms of mercurial neurotoxicity.
Keywords: Dimercaprol - therapeutic use, Electric Organ - enzymology, Electrophorus - physiology, Mercury Poisoning - enzymology, Mercury Poisoning - prevention & control, Chelating Agents - therapeutic use, Choline O-Acetyltransferase - metabolism, Dimercaprol - therapeutic use, Electric Organ - enzymology, Electrophorus - physiology, Kinetics, Mercury Poisoning - prevention & control
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