Metal transfer as a mechanism for metallothionein-mediated metal detoxification

High kinetic reactivity and high metal affinity of the metal-binding sites of metallothionein are characteristics that would facilitate involvement of the thionein-zinc metallothionein couple in metal transfer or exchange rea ctions. Studies demonstrating thionein-metallothionein-mediated activation or inhibition of various zinc metalloenzymes and transcription factors prov ide support for a potential role for metallothionein in metal transfer reac tions with receptor molecules. Although a role in basal zinc regulation is currently a topic of debate, less controversial is a role for metallothione in in the detoxification of metals such as cadmium. The toxicity of metals can, in part, be due to adventitious binding to charged sites of target pro teins or the displacement of zinc bound to zinc metalloproteins, Zinc metal lothionein has the capability of repairing such structures through abstract ion of a toxic metal in the former case or through a reciprocal metal trans fer reaction that involves abstraction of the toxic metal and donation of t he essential metal zinc in the latter. This would confer on metallothionein an active role in the protective response to metal toxicity, rather than a passive one that is solely dependent on the high metal affinity for bindin g free metal ions. The efficacy of such a mechanism for metal detoxificatio n has been demonstrated with enzymes, actin and zinc finger proteins. With zinc finger proteins, zinc metallothionein can restore both altered seconda ry structure and inhibited DNA-binding function to functional states throug h a zinc for cadmium exchange.