Inactivation of microsomal Ca(2+)-ATPase by 2-chloroethylethyl sulfide.
Exposure of liver microsomes to 2-chloroethylethyl sulfide (CEES) led to a dose-dependent decrease of Ca(2+)-ATPase activity. Studies on a structural requirement and a time dependence suggest that the enzyme inhibition may proceed via an instantaneous process involving an alkylation by an unstable intermediate, presumably a sulfonium form. It is noteworthy that the microsomal Ca(2+)-ATPase was more sensitive to CEES than the Na+/K(+)-ATPase from erythrocyte membranes. The Ca(2+)-ATPase was inhibited non-competitively by CEES, and its inhibitory action was independent of Ca2+ concentrations. The involvement of membrane phospholipid in the enzyme inhibition is excluded, since the temperature dependence of microsomal Ca(2+)-ATPase was not affected by CEES. Moreover, Triton X-100-solubilized Ca(2+)-ATPase was inactivated by the compound to the same extent as the membrane-bound enzyme was. Thus, it is suggested that CEES inactivates Ca(2+)-ATPase by alkylating the enzyme molecule at a region other than the active site.
Kim
Y B
YB
Advanced Technology Research Center (#6-7), Agency for Defense Development, Taejon, South Korea.
Lee
Y S
YS
Choi
D S
DS
Cha
S H
SH
Sok
D E
DE
D000255:Adenosine Triphosphate / Q000378:metabolism; D000478:Alkylation; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009151:Mustard Gas / Q000031:analogs & derivatives* / Q000633:toxicity; D017830:Octoxynol / Q000494:pharmacology; D013696:Temperature
D004791:Enzyme Inhibitors; C031278:2-chloroethyl ethyl sulfide; D000255:Adenosine Triphosphate; D017830:Octoxynol; D000252:Calcium-Transporting ATPases; D002118:Calcium; D009151:Mustard Gas