Studies on the toxicity of copper. II. The behaviour of microsomal membrane ATP ase of the pigeon’s brain tissue to copper and some other metallic substances

Abstract

Earlier work on the toxicity of copper (Cu 2+ ) in vivo suggested that the metal exerted its effect on the cell membrane, probably the microsomal ATP ase. The microsomal ATP ase prepared from pigeon brain is activated by Mg but little by Na and K. 20 µ m Cu achieved maximum inhibition reducing enzyme activity by approximately 25%. The same preparation was only slightly sensitive to ouabain, the effects of copper and ouabain were not additive. The toxicity of cadmium approached that of copper. Cobalt and thorium were not toxic in the concentration range studied. The microsomal ATP ase appears to have a thiol group at the active catalytic centre. It is potentiated by the thiols, BAL , penicillamine, dithiocarbamate and thioctic acid. Only with thioctic acid was there any reversal of Cu 2+ toxicity. We conclude that there are at least three components in the pigeon’s brain microsomal ATP ase : (1) resistant to copper and to ouabain, (2) inhibited by copper, only slightly inhibited by ouabain (3) stimulated by -SH compounds, sensitive to ouabain and copper. We also conclude that inhibition of membrane ATP ase may be responsible for the excitatory effect of Cu 2+ in vivo .