The binding of Gold(I) to metallothionein.
The binding of gold(I) to metallothionein, MT, has been unambiguously established by the reaction of Na2AuTM with purified horse kidney MT. Zinc was displaced more readily than cadmium although the latter could be displaced using large Au/Cd ratios. The metal exchange reactions were complete within 2 hr of mixing. Further evidence that such reactions might be physiologically significant were obtained by studying in vitro metal displacements in the liver cytol of in vivo metal treated rats: When Na2AuTM was added to the cytosol of rats administered CdCl2 in vivo, zinc, copper and cadmium were displaced in 2/1/1 ratios from the metallothionein fraction. The zinc and cadmium displacement provide direct evidence that the gold was binding to MT. Addition of Cd+2 to liver cytosol of gold-treated rats resulted in displacement of copper and zinc, but not gold, from the MT fractions. When liver MT is prepared from rats exposed to Au or Cd, the Cd/protein ratio increased during the preparation, but the Au/protein ratio decreased. The Mt-bound metals account for 95% of the cytosolic Cd but only 15%-30% of the cytosolic gold in these studies. Thus, the nonspecific binding of gold to MT in vivo should be considered as one aspect in its equilibration among protein binding sites, which include, inter alia, metallothionein. Gold was found to coelute with zinc and cadmium in the MT fraction of rat kidney cytosol, when both Cd and Na2AuTM were administered to the rats. The possible significance of gold binding to MT in the treatment of rheumatoid arthritis--chrysotherapy--is briefly discussed.
D000818:Animals; D002104:Cadmium / Q000378:metabolism / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D006046:Gold / Q000378:metabolism / Q000494:pharmacology; D006736:Horses; D007668:Kidney; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008667:Metalloproteins / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats
D008667:Metalloproteins; D002104:Cadmium; D006046:Gold; D008668:Metallothionein