Heavy Metal Toxicity and Essentiality

High concentrations of heavy metals that affect, directly or indirectly, the redox potential in the reducing intracellular milieu, particularly copper, induce the formation of reactive oxygen species. These, in turn, can trigger the chain reaction causing lipid peroxidation, which affects membrane integrity and induces structural changes to proteins and nucleic acids that can result in cell death. 

This chapter reviews current knowledge of copper homeostasis, with particular emphasis on the role of mammalian copper P-type ATPases in that process. 

Hundreds of mutant P-type ATPases have been generated in an effort to understand the catalytic mechanism and regulation of these enzymes. Functional analysis of these mutants has established the roles of particular domains and amino acid residues in the overall catalysis of cation translocation and allowed structure prediction (MacLennan etal., 1997) (Figs. 1 and 2). Recently the 3-D or crystal structures of Ca +, H+, and Na+/K+ P-type ATPases have been resolved, and they confirmed findings 

An important characteristic of P-type ATPases is their ability to be transiently phosphorylated at the invariant aspartate residue by inorganic orthophosphate in the absence of the cation (Fig. 2, step 5). A diagnostic inhibitor of P-type ATPases, ortho vanadate, can also bind to the invariant aspartate but, unlike orthophosphate, cannot participate in the reaction cycle (Carafoli, 1991 MacLennan ei a/., 1997). 

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