Membranes toxic metals, interaction

A variety of responses can be initiated by the direct interaction of metals with cellular components. Membrane damage and enzyme inhibition are examples of such a metal effect. Above a certain threshold concentration of metals in the cell, its physiological state is irreversibly changed (Van Assche et al., 1988). This response is reflected by an increase in capacity (activity under non-limiting substrate and coenzyme concentrations) of certain enzymes. This increase in capacity is generally called enzyme induction. These secondary, indirect effects of metals are considered to play an important role in the stress metabolism induced by toxic metal concentrations. 

The ability of toxic metals to increase membrane permeability to cations, and in particular to K, is well established (Rothstein 1970) however, it is not known whether these cation-selective pathways also function to transport the toxic metals across the membrane. Changes in cation permeability appear to be the result of an interaction of toxic metals with sulfhydryl groups of membrane proteins that modulate cation permeability (Ballatori et al. 1988 Jungwirth et al. 1991a,b Kone et al. 1988, 1990). These proteins have not yet been identified. 

Considering additionally that the risk assessment of mixtures is presently an urgent issue, and that usually mixtures of exclusively organic chemicals or exclusively metals are investigated, in future more emphasis should be placed on the interactions of xenobiotic HIOCs with metals. Major research questions will include how these interactions influence bioavailability of both metals and HIOCs, interactions with biological membranes, uptake, and common toxic effects. 

While Davis and his colleagues illustrated the significance of soil metal speciation in risk assessment, Morrison et al. (1989) pointed out that the toxicity of metals is related to the forms in which they exist in the aqueous phase. This is because the interaction of metals with intracellular compartments is highly dependent on chemical speciation. Some species may be able to bind chemically with extracellular proteins and other biological molecules, some may adsorb onto cell walls, and others may diffuse through cell membranes. Consequently, toxicity is more related to the concentrations of metals in a particular species, than to the total concentrations. Geochemical modeling... 

In Table 9.1, the various metals are grouped according to their reactions with DNA, and the involvement of several metal ions in more than one of those mechanisms of action are listed. This is particularly evident for Cd(II), Co(II), Cr(III), Ni(II), Zn(II), As(III), Hg(II), and V(IV). Many of these reactions are associated with the valency of the metal ions under consideration (they are particularly well documented for Cr Cohen et al. 1993), and with their ionic strength . From a more genetic viewpoint, the interaction also depends on a metal s ability to cross cellular membranes and its availability in an amount which is sufficient for the respective reaction but is not too toxic. In many cases, low concentrations of metal ions are those rendering their reaction with DNA possible. 

The physiological result of the binding of the non-essential lanthanide and actinide metals to albumin, or transferrin, in the blood plasma may well be that the metals are held in a form in which they are virtually unable to penetrate the cell membrane in ionic form thus limiting cellular uptake and also the ability to cause harmful effects by interaction with essential enzymes or other proteins. Thus for the non-essential f elements, protein binding may be regarded as part of a protective mechanism against chemical toxicity,... 

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