Inorganic mercury interacts with thiols at the nucleotide and cationic binding sites of the ouabain-sensitive cerebral electrogenic sodium pump

The molecular events leading to neuronal dysfunction often associated with mercury toxicity can be complex and is yet to be fully elucidated. Hence, the present study sought to evaluate the interaction of inorganic mercury (Hg2+) with the ouabain-sensitive electrogenic pump in partially purified mammalian brain membrane preparations. The results show that Hg2+ significantly inhibited the transmembrane enzyme in a concentration dependent manner. In addition, Hg2+ exerts its inhibitory effect on the activity of the enzyme by interacting with groups at the adenosine triphosphate (ATP), Na+ and K+ binding sites. However, preincubation of the enzyme with exogenous monothiols, cysteine, prevented the inhibition of Hg2+ on the pump's activity suggesting that Hg2+ may be interacting with the thiols at the nucleotide (ATP) and cationic (Na+ and K+) binding sites. In fact, our data show that Hg2+ oxidizes sulphydryl groups in cysteine in a time dependent fashion in vitro. Finally, we speculate that the small molecular volume of Hg2+ in comparison with the substrates (ATP, Na+ and K+) of sodium pump, its possibly high reactivity and strong affinity for thiols may account for its high toxicity towards the membrane bound ouabain-sensitive electrogenic pump.

► Cerebral sodium pump contains thiols located at Na+, K+, and ATP binding sites.
► Hg2+ binds these critical thiols on sodium pump, thus inhibiting its activity.
► Cysteine prevents Hg2+ binding to thiols on cerebral electrogenic sodium pump.
► Cysteine could not relieve Hg2+ inhibition of cerebral sodium pump.