INACTIVATION OF MICROSOMAL CA2-ATPASE BY 2-CHLOROETHYLETHYL SULFIDE()

Exposure of liver microsomes to 2-chloroethylethyl sulfide (GEES) led to a dose-dependent decrease of Ca2+-ATPase activity. Studies on a str uctural requirement and a time dependence suggest that the enzyme inhi bition may proceed via an instantaneous process involving an alkylatio n by an unstable intermediate, presumably a sulfonium form. It is note worthy that the microsomal Ca2+-ATPase was more sensitive to GEES than the Na+/K+-ATPase from erythrocyte membranes. The Ca2+-ATPase was inh ibited non-competitively by GEES, and its inhibitory action was indepe ndent of Ca2+ concentrations. The involvement of membrane phospholipid in the enzyme inhibition is excluded, since the temperature dependenc e of microsomal Ca2+-ATPase was not affected by GEES, Moreover, Triton X-100-solubilized Ca2+-ATPase was inactivated by the compound to the same extent as the membrane-bound enzyme was. Thus, it is suggested th at GEES inactivates Ca2+-ATPase by alkylating the enzyme molecule at a region other than the active site.