Molecular and ionic mimicry of toxic metals.

Abstract

The landmark review by Wetterhahn-Jennette (1) laid the foundation for this review. A recent review on mechanisms of metal transport (2) has also been an important literature resource. Wetterhahn-Jennette pointed out the structural similarities of many oxyanions and explained the toxicities of several metals in terms of oxyanions competing with endogenous oxyanions, phosphate, and sulfate in transport, enzymatic and receptor-mediated processes. She also introduced the term to describe the competition between many divalent endogenous and toxic metal ions in biological systems, such competition giving a mechanistic insight into the toxic action of certain metals. The term has been mainly confined to the field of immunology. In the context of this review, the term roolecular mimicry is restricted to those examples in which a toxic metal forms a complex with an endogenous ligand such that the resulting compound mimics the behavior of a normal substrate. An example to be discussed in some detail is the reaction of the methylmercury cation with the amino acid cysteine to form a compound that mimics the amino acid methionine and thus gains entry into the cell on an amino acid carrier. This review updates the literature on both oxyanion and divalent metal competition and introduces a new extension of molecular and ionic mimicry to complexes formed by mercury that are structurally similar to and biologi­ cally mimic endogenous molecules. This review is not intended to be an exhaustive account of all the literature but gives examples that illustrate the role of molecular and ionic mimicry in the action of the toxic metals.