EFFECTS INVITRO OF MERCURY ON RAT-BRAIN MG++-ATPASE

Mercuric chloride (Hg) in micromolar concentrations inhibited Mg++-dependent ATPase activity in rat brain microsomes. Inhibition was higher in oligomycin-sensitive (O.S.) than oligomycin-insensitive (O.I.) Mg++-ATPase. Hydrolysis of ATP with 15 and 50-mu-g of microsomal protein for 45 min without and with (2.10(-7) M) Hg showed linear rates for 15-20 min. Altered pH vs activity demonstrated comparable inhibitions by Hg in buffered (neutral > acidic > basic) pH ranges. Inhibition of enzyme activity by Hg was found to be greater at 37-degrees-C than at lower temperatures suggesting positive correlation trend. An uncompetitive inhibition with respect to the activation of Mg++-ATPase, O.S. Mg++-ATPase and O.I. Mg++ ATPase by ATP was indicated by a decrease in apparent V(max) and K(m). Mg++-activation kinetic studies indicated that Hg causes uncompetitive inhibition of Mg++-ATPase and O.I. Mg++-ATPase and mixed inhibition of O.S. Mg++-ATPase. Inhibition was partially restored by repeated washings. These results indicate that the inhibition of microsomal Mg++-ATPase by Hg was pH, temperature, enzyme, and Mg++ concentration dependent. Additionally, the data also suggest that O.S. compared to O.I. Mg++-ATPase is more sensitive to Hg toxicity.