Nonessential metals

Heavy metals with no known biological function, such as aluminum, arsenic, lead, and mercury, are nonessential metals.4-5 These metals are toxic because they can irreversibly bind to enzymes that require metal cofactors. Toxic metals readily bind to sulfhydryl groups of proteins.6-7 In fact,... 

All metals, regardless of whether they are essential or nonessential, can exhibit toxic effects at high concentrations.14-16 Excess concentrations of essential metals can lead to nonspecific binding, which can affect the enzyme structure and function. Because controlling metal concentrations is vital for maintaining homeostatic conditions within bacterial cells, evolution has bestowed upon organisms a number of ways to regulate concentrations of essential metals and to resist the toxicity of nonessential metals.17-20... 

There are a number of different mechanisms by which microorganisms resist metal toxicity (Table 11.1). Five mechanisms that microbes use to mediate metal toxicity have been proposed and they include (1) formation of a permeability barrier,21-24 (2) active transport,25-29 (3) sequestration,30-32 (4) enzymatic detoxification,33 34 and (5) reduction in sensitivity.35,36 Microbes may use one or more of these mechanisms to exclude nonessential metals and regulate internal concentrations of essential metals. 

This cascade in research is reflected in the increasing amount of literature published each year on the biochemical behavior of the lithium ion and the aim of this article is to bring together much of this information, emphasizing the ubiquity of this small, apparently nonessential, metal cation in biology. 

The AE methods have been used to determine the effects of different algae as food sources in the bioaccumulation of radiolabelled essential (Co, Se, Zn) and nonessential trace metals (Ag, Am, Cd, Cr) in the mussel Mytilus edulis [94]. Assimilation of essential metals was correlated with carbon assimilation, but not nonessential metals. The distribution of the metal in the alga and the gut passage time in the mussel was found to be important. 

Transport of a nonessential metal ion across a biological membrane kml = nr4s) 104... 

Once inside the organism, organic chemicals and metals are dealt with differently. Organic chemicals generally distribute based on their chemical properties (e.g., molecular size, lipophilicity, stereochemistry) and are eliminated through metabolism (phases I and II) or excretion (for example, renal excretion in mammals) of either the parent compound or the metabolites. Metals, on the other hand, can be split into essential and nonessential elements. Biochemical mechanisms and pathways have evolved to regulate essential metals with physiological functions. However, nonessential metals due to physicochemical similarities also use some of these pathways and thus affect the homeostasis of essential metals. 

A classic example of essential metal deficiency resulting from nonessential metal exposure is Itai itai disease. Cadmium pollution in the Jinzu River basin in Japan resulted in severe nephrotoxicity in approximately 184 people. Renal tubule damage caused excessive loss of electrolytes and small proteins from the urine. In severe cases, urinary Ca loss was so severe that bone Ca was mobilized, resulting in osteomalacia. Renal tubular defects persisted for life and induced hypophosphatemia, hyperuricemia, and hyperchloremia, which are characteristic biochemical features of Itai-itai disease (see Section 21.6.1). 

The majority of this chapter focuses on the toxicology of nonessential metals. Cadmium, lead, and mercury are three nonessential metals that have been investigated in great detail over the years, and they will be highlighted below. Other nonessential metals such as aluminum, beryllium, and nickel have not received as much attention but can pose toxicity issues. Arsenic and selenium are technically not metals, but are often included in discussions of metal toxicology. These elements will not be discussed here. 

Metallothioneins (MTs) are a superfamily of low-molecular-weight (<7000-dalton) intracellular metal-binding proteins, which, in many species, play a critical role in (a) the detoxification of nonessential metals such as Cd2+ and Hg2+ and (b) the regulation of intracellular concentrations of essential metals such as Zn2+ and Cu+. In 1957, Kagi and Vallee first purified and characterized MT as a cadmium-binding protein in equine kidney. 

Essential and Nonessential Metals. It is well known that elements in the biological systems may vary a great deal in their concentration from organ to organ and from species to species, but for the purpose of this chapter, the following classification of elemental concentrations has been adopted (17) major, > 1% minor, 0.10-1% micro, 0.01-0.1% trace, 0.01-0.001% ultratrace, < 0.001%. Since total copper in the average, "standard man (18) is approximately 150 mg (2), its classification would fall between trace and ultratrace concentration. However, as is the case with any other element, what is a trace in one organ may be an ultratrace in another, but for serum copper concentration, which is about 100 /xg%, the definition of copper as an ultratrace metal by the above classification may not be justifiable. If the criteria of the "standard man is taken into account, however, the definition seems appropriate. 

The tentative tolerable daily intakes proposed for certain metals provide a guideline for maximum tolerable exposure. In the case of essential elements, these levels exceed the daily requirements, but this should not be construed as an indication of any change in the recommended daily requirements. In the case of both essential and nonessential metals, the tentative tolerable intake reflects permissible human exposures to these substances as a result of natural occurrence in foods or various food processing practices, as well as exposure from drinking water. 

Heavy metal ions such as Cu, Zn, Mn, Fe ", NP", and Co are essential micronu-tritients for plant metabolism. When these ions are not available to the roots, plants develop specific deficiency symptoms, though when present in excess, these - as well as nonessential metals such as Cd ", Hg " and Pb " " - can become extremely toxic. At high concentrations, all these metals may cause symptoms such as chlorosis and necrosis, stunting, leaf discoloration and inhibition of root growth (Marschner... 

Trace metals can be divided into three categories those known to be dietary essentials, those possibly essential, and nonessentials. Metals known to be essential to higher animals include chromium, cobalt, copper, iron, manganese, molybdenum, selenium, tin, vanadium, and zinc. Several additional metals considered as possibly essential on the basis of suggestive but inconclusive evidence include arsenic, barium, cadmium, nickel, and strontium. The other metals are presently classified as nonessential. 

Proteins involved in metal ion homeostasis can be divided into two broad families, metal trafficking proteins and metalloregulatory proteins. The metal trafficking proteins include membrane transporters that translocate metal ions across cell membranes and soluble metallochaper-one proteins that deliver metal ions to specific target proteins. The metalloregulatory proteins utilize metal ions to regulate gene expression." Proteins in both families maintain concentrations of both essential and nonessential metal ions. The coordination chemistry of metal homeostatic... 

The present section, which also comprises an update of earlier overviews," focuses on the coordination aspects of these metals in biopolymers, both in their natural environments (e.g., bound to proteins and nucleic acids) and on the effect of nonessential metal compounds on these biological macromolecular systems. 

Soto-Jimenez MF, Amezcua F, Gonzdlez-Ledesma R (2010) Nonessential metals in striped marlin and Indo-Pacific sailfish in the Southeast Gulf of Cahfomia, Mexico concentration and assessment of human health risk. Arch Environ Contam Toxicol 58 810-818... 

There are two isomers of metallothionein in mammalian cells MT-1 and MT-2. There are several metallothionein genes. The transcription of each is controlled by several heavy-metal response elements or by hormone response elements [14,15]. The mechanism of control of the metallothionein genes by its promoters is a subject of intense investigation. Despite all the knowledge gained so far, the function of the metallothionein is still uncertain. However, it appears that the metallothionein may play key roles in the homeostasis of zinc within cells and in the detoxification of excess copper or toxic nonessential metals like cadmium and mercury. 

Krantzberg, G. 1989. Accumulation of essential and nonessential metals by chironomid larvae in relation to physical and chemical properties of the elements. Can. J. Pish. Aquat. Sci. 46 1755-1761. 

The placenta provides the route of transfer of both essential and nonessential metals from mother to fetus. It is now recognized that for many toxic metals adverse health effects occur at levels not previously thought to be toxic and that the developing fetus and newborn are particularly vulnerable. Emerging questions that must be addressed concern the lowest levels of exposure that produce toxicity. Are there, in fact, thresholds for such effects, or is the failure to detect effects in the newborn merely a reflection of the inability to recognize or detect subtle effects Are such effects of longer term consequence, that is, are they reversible And, finally, what are some of the avenues for intervention including nutrition ... 

At an appropriate dosage, both essential and nonessential metals may be toxic. 

Nonessential metals are found in the same columns of the periodic table as are the essential metals. For example, the essential micronutrient copper is found in the same column as the elements silver and gold, both of which are toxic. Likewise, the essential metal zinc is found in the same column of the periodic table as the toxic... 

For many metal ions, particularly those within the same column of the periodic table, the need for essential metal ions runs counter to the need to minimize the uptake of toxic, nonessential metal ions. For example, the epithelial layers of the intestine have to remain... 

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