Roles of metallothionein and related proteins in metal metabolism and toxicity: problems and perspectives

Abstract

This summary examines some of the known and hypothesized roles of metallothionein and related proteins in mediating the metal metabolism and toxicity from a chemical perspective. It attempts to examine in kinetic terms how such molecules may exert homeostatic control over the intracellular bioavailability of metal ions to essential enzymatic or other molecular systems. The concept of ongoing competition between metallothionein and related proteins with other intracellular metal-binding sites for various metals is also examined in relation to the thermodynamic stability of these proteins. Comparisons between mammalian metallothionein and analogous nonmammalian proteins demonstrate both similarities and great differences in types of metal-binding sites, metal-binding constants, amino acid composition, and secondary structures such that apparent diversity of these low molecular weight metal-binding molecules in nature appears to be growing ever wider. The potential value of these data rests both in delineating new hypotheses for metallothionein evolution and in suggesting new model systems for discovering the normal function of metallothionein and related proteins in cells.