Stimulation of mouse liver corticosteroid side chain isomerase by cobaltous and nickelous ions: evidence for an endogenous inhibitor of isomerase activity.
Corticosteroid side chain isomerase of mouse liver cytosol was stimulated by Co2+ and Ni2+. The magnitude of stimulation increased with incubation time. For Co2+ and Ni2+, respective enhancements were 2.8- and 4.0-fold at 15 min and 3.9- and 5.0-fold at 60 min. The relationship between steroid substrate concentration (11-deoxy-[21-3H]corticosterone) and initial velocity was consistent with a model in which the cations reacted with a cytosol inhibitor of isomerase activity. Enzyme, partially purified by ammonium sulfate fractionation and gel filtration, had a 6.8-fold increased specific activity. Co2+ and Ni2+ enhanced the activity of partially purified enzyme 1.6- and 1.9-fold. Unlike the cytosol, stimulation was achieved without lag and was not altered by prolonged incubation. Metal ion chelating agents did not have a consistent effect on the activity of the partially purified enzyme. Cyanide and alpha,alpha-dipyridyl increased, and dithizone and 8-hydroxyquinoline decreased activity. The data are not consistent with the hypothesis that side chain isomerase is a metalloenzyme. It is concluded that Co2+ and Ni2+ stimulate the enzyme by removing an endogenous inhibitor.
D000818:Animals; D002384:Catalysis; D002413:Cations, Divalent / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology*; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D007535:Isomerases / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009532:Nickel / Q000494:pharmacology*; D013251:Steroid Isomerases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D002413:Cations, Divalent; D002614:Chelating Agents; D003035:Cobalt; D009532:Nickel; D007535:Isomerases; C047770:corticosteroid side-chain-isomerase; D013251:Steroid Isomerases