Recent excitement regarding metallothionein

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Abstract
Metallothionein (MT) was discovered 40 years ago (1). By all accounts it is a most unusual and unconventional protein (2–6). One-third of its 60+ amino acids are cysteines and eight are lysines; it contains neither aromatic amino acids nor histidine. MT usually binds seven zinc atoms, but it also can contain copper, cadmium, and traces of other metals. In an evolutionary sense it is a very old protein, and the composition of its two major isoproteins has changed only imperceptibly over time. The number of genes that code for human MTs could be as high as 17. MT-1 and MT-2 are the two prevalent forms: they are expressed but their physiological functions are still unknown. MT-3 was discovered only recently in brains from patients afflicted with Alzheimer’s disease (7), a discovery based on the fact that MT-3 inhibits the growth of neurons. Thus far, it is the only isoform that is known to exhibit such a specific biological function; it contains zinc and copper (I), but not cadmium. Multiple factors, including members of the nuclear hormone receptor family, interferons, inducers of the acute phase response and metalloregulatory proteins, affect tissue-and isoprotein-specific gene expression. In addition, MT is induced by numerous other agents whose signaling pathways remain obscure. Thionein, the apoform of MT has never been isolated as such from any biological source. Apparently, at its formation, it instantaneously combines with zinc, whose “free” concentration in the cell has been reported to be exceedingly low, …