Generally, metals produce their biological toxicity by forming complexes or "ligands" with organic compounds. These modified biological molecules lose their ability to function properly; the affected cells either malfunction or die. The most common groups involved in ligand formation are oxygen, sulfur, and nitrogen. When metals bind to these groups, they affect protein structure or render important enzyme systems inactive. Patients with a metal-metabolism disorder can be especially at risk since they tend to accumulate, rather than eliminate, these toxins.

Toxic metals tie up the cysteine in our food and, when the protective endogenous thiols (metallothionine and glutathione) are saturated, they trap proteins, peptides, enzymes, lipoic acid, and other thiols critical to the proper functioning of our bodies. This causes nutritional deficiencies of critical amino acids, enzymes, and minerals necessary for numerous metabolic functions.

The sulfhydryl-reactive metals (As, Cd, Pb, Hg, and Pd) have three major properties that mechanistically explain how they elicit a majority of their toxic effects. First, they are transition metals that promote the formation of hydrogen peroxide and enhance the subsequent iron- and copper-induced production of lipid peroxides and the highly reactive hydroxyl radical. Lipid peroxides alter membrane structure and are highly disruptive of mitochondrial function. 

The pro-oxidant properties of the metals are exacerbated by their inhibitory effects on antioxidant processes. Hg and Cd have high affinities for glutathione (GSH), which is the primary intracellular antioxidant and conjugating agent. Importantly, a single atom of Cd or Hg can bind to, and cause the irreversible excretion of, up to two GSH tripeptides. The metal-GSH conjugation process is desirable in that it results in the excretion of the toxic metal into the bile. However, it can deplete the cell of GSH and thus decrease antioxidant capacity. Lead-induced depletion of intracellular GSH and increased levels of malondialdehyde in the brain and liver have been demonstrated in animal models. It has also been demonstrated that Hg not only directly removes GSH from the cell, but also inhibits the activities of two key enzymes involved in GSH metabolism: GSH synthetase and GSH reductase. Hg also inhibits the activities of the free radical quenching enzymes catalase, superoxide dismutase, and perhaps GSH peroxidase. The inhibition of GSH peroxidase has been attributed to the formation of a mercury-selenide complex. Selenium is an integral component of GSH peroxidase. 

Certain “transition metals” like nickel, cadmium, mercury and palladium are carcinogenic to humans. However, certain mechanisms of their carcinogenic activity remain obscure. One possible mechanism would involve metal-mediated promutagenic oxidative damage to DNA and nuclear proteins. Another would include adverse effects on the fidelity of DNA replication and repair processes, as well as derangement of gene expression and cell signaling, through interactions with essential metals and/or induction of conformational changes in biomolecules. 

As with all metals, these “transition metals” are both ductile and malleable, and conduct electricity and heat. The interesting thing about transition metals is that their valence electrons, or the electrons they use to combine with other elements, are present in more than one shell. This is why they often exhibit several common oxidation states. And it is this unique ability that allows them to inhibit antioxidative processes and thereby create reactive oxygen toxic species (ROTS). In general, the transition metals promote excessive production of lipid peroxides and hydroxyl radicals that inhibit antioxidative enzymes. These also inhibit a plethora of other enzyme families by virtue of their high affinity for free sulfhydryl groups (e.g. Creatinine kinase, Na/K ATPase). The metals deplete intracellular glutathione (GSH), and inhibit enzymes involved in the synthesis and metabolism of the important antioxidant and metal-conjugating peptide. Though this site introduces only 5 of the 38 transition metals (cadmium, copper, mercury, nickel, and palladium) there are other potentially toxic transition metals noteworthy of mention: iron, cobalt, gold, manganese, chromium, and tungsten.

The elements classified as "other metals" are ductile and malleable; they are not the same as the transition elements. These elements, unlike the transition elements, do not exhibit variable oxidation states, and their valence electrons are only present in their outer shell. All of these elements are solid, have a relatively high density, and are opaque. They have oxidation numbers of +3, ±4, and -3. Of these, we have links to aluminum and lead on this site; other noteworthy potentially toxic metals in this category are tin, bismuth and thallium.