Role of Metallothionein in Cadmium Metabolism

Abstract

Induction of the synthesis of the metal-binding protein, thionein, is not only a particularly interesting feature of the biochemistry of the cadmium (Cd) ion, but also of considerable importance in relation to its metabolism and chronic toxicity. As Cd is neither an abundant element, nor readily absorbed through the mammalian gastrointestinal tract, normally only small amounts of it are transmitted through the food chain to animals and humans. Nevertheless, much of the absorbed Cd is retained, principally in the liver and kidneys and, even in uncontaminated environments, long-lived animal species may accumulate appreciable body burdens during their lifetimes. Earlier studies, reviewed by Vallee (1979) had shown the presence of Cd in a wide variety of biological tissues, relatively high concentrations usually being present in human and equine renal cortex. A search for a possible biochemical function of this seemingly biologically ubiquitous element led to the isolation from horse kidney of a low molecular weight protein, deficient in aromatic amino acids, which not only had a high content of Cd (20–25 mg per gram protein), but also contained most of the Cd in the tissue (Margoshes and Vallee 1957). Subsequent preparations of the metalloprotein by improved methods (Kägi and Vallee 1960, 1961) were found to contain 5% Cd, 2.2% Zn, 0.4% Fe, 0.18% Cu, 14.9% N, and 8.5% S. Because of the presence of several metals, in addition to Cd and the high sulphur content Kägi and Vallee (1960) named the metalloprotein “metallothionein”, i.e. a metallo-derivative of the sulphur-rich protein, thionein.